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Actos (pioglitazone HCl) - Eli Lilly & Co.

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• Pioglitazone at ReliableRXPharmacy

 Related Topics:

• Actos (pioglitazone HCl) / Amaryl (glimepiride) / Avandia (rosiglitazone) / Byetta (exenatide) / Diabeta, Micronase (glyburide) / Farxiga (dapagliflozin) / Glucophage (metformin) / insulin / Invokana (canagliflozin) / Januvia (sitagliptin) / Jardiance (empagliflozin) / Lantus (glargine) / Onglyza (saxagliptin) / Prandin™ (repaglinide) / Precose (acarbose) / Rezulin (troglitazone) / Starlix® (nateglinide) / Symlin (pramlintide acetate) / Victoza (liraglutide)

News & Research:

• Diabetes Drug Tied to Lower Dementia Risk - Medscape, 2/26/23 - "There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio [aHR], 0.84 ... A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72" See pioglitazone at ReliableRXPharmacy.
• Pioglitazone corrects dysregulation of skeletal muscle mitochondrial proteins involved in ATP synthesis in type 2 diabetes - Metabolism 2020 Oct 30 - "skeletal muscle (SKLM) ... Type 2 diabetes is associated with reduced levels of mitochondrial proteins involved in oxidative phosphorylation and an increased abundance of enzymes implicated in fatty acid catabolism in SKLM. PIO treatment is able to improve SKLM mitochondrial proteomic profile in subjects with T2DM" - See pioglitazone at ReliableRXPharmacy.
• Diabetes drug relieves nicotine withdrawal - Science Daily, 11/4/19 - "The diabetes drug, pioglitazone, targets a specific form of the peroxisome proliferator-activated receptors in the nucleus. This receptor, PPARγ, is found in areas of the brain involved in drug addiction"
• Pioglitazone Exposure Reduced the Risk of All-Cause Mortality in Insulin-Treated Patients with Type 2 Diabetes Mellitus - J Clin Endocrinol Metab. 2019 Sep 23 - "After adjustment for age, sex, comorbidities, Diabetes Complications Severity Index scores, and drugs used, mortality rates were 30.26 and 15.02 per 1000 person-years for pioglitazone nonusers and users, respectively. The adjusted hazard ratio (aHR) of mortality was 0.47 (95% confidence interval [CI]: 0.38-0.58, p < 0.001) for pioglitazone users compared with nonusers. The aHRs of CV and non-CV deaths were 0.78 (95% CI: 0.51-1.19) and 0.50 (95% CI: 0.38-0.66), respectively. The aHRs of hospitalized coronary artery disease, hospitalized stroke, and incident heart failure were not significantly different between pioglitazone users and nonusers"
• Carotid intima-media thickness and markers of brain health in a bi-racial middle-aged cohort: CARDIA Brain MRI Sub-study - J Gerontol A Biol Sci Med Sci. 2019 Feb 23 - "cerebral blood flow (CBF) ... This study suggests that lower CBF in middle-age is associated with markers of atherosclerosis in the carotid arteries. This association may reflect early long-term exposure to traditional cardiovascular risk factors. Early intervention on atherosclerotic risk factors may modulate the trajectory of CBF as people age and develop brain pathology"
• Diabetes drugs act as powerful curb for immune cells in controlling inflammation - Science Daily, 7/28/18 - "Keeping macrophages from going overboard on the job may inhibit the onset of obesity and diabetes following tissue inflammation ... Lazar's team found that the TZDs, working through PPAR gamma, promote the metabolism of an amino acid called glutamine, a protein building block necessary for macrophage activation. The team found that macrophages lacking PPAR gamma are unable to use glutamine as an energy source and therefore are more susceptible to inflammatory stimulation"
• IRIS: New Analysis Finds Best Candidates for Pioglitazone After Stroke - Medscape, 9/26/17 - "in patients with recent ischemic stroke or TIA and insulin resistance, pioglitazone reduced recurrent stroke or MI by about one fourth compared with placebo"
• The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement - Metabolism. 2017 Jun;71:17-3 - "The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients"
• Pioglitazone May Improve NASH Histology for Many Patients - Medscape, 2/15/17 - "Nonalcoholic steatohepatitis is becoming a major public health issue and is a leading cause of liver transplant ... treatment with the antidiabetic drug pioglitazone reverses the more advanced stages of liver disease in NASH regardless of the presence of diabetes, which provides a rationale for evaluating the effect of this drug on clinical outcomes in this subgroup of patients at higher risk of liver-related complications ... the combined results for all studies showed that treatment with thiazolidinedione therapy improved advanced fibrosis by more than threefold compared with no treatment"
• Pioglitazone Diabetes Prevention Data Now Published - Medscape, 8/12/16 - "The now-generic glucose-lowering drug pioglitazone cuts the risk of developing diabetes in half among people with insulin resistance and cerebrovascular disease"
• Pioglitazone Improves Fatty Liver in Prediabetes, Diabetes - Medscape, 7/5/16 - "Long-term treatment with the thiazolidinedione pioglitazone is safe and effective for patients with prediabetes or type 2 diabetes and nonalcoholic steatohepatitis (NASH) ... found long-term metabolic and histologic improvement associated with 3 years of pioglitazone, suggesting this drug may halt NASH progression and alter the natural history of the disease"
• Pioglitazone Slows Progression to Type 2 Diabetes: More IRIS Data - Medscape, 6/17/16 - "Pioglitazone halved the progression to diabetes in people with insulin resistance and cerebrovascular disease ... pioglitazone reduced by a significant 24% the risk for recurrent stroke or myocardial infarction (MI) in people with insulin resistance, no frank diabetes, and a recent history of stroke or transient ischemic attack ... Pioglitazone also previously showed cardiovascular benefit in the 2005 PROactive trial, with a significant 16% reduction in death, MI, and stroke ... Pioglitazone is the only oral type 2 diabetes drug with clear antiatherosclerosis effects ... ACT NOW lead author, believes the time is right to take another look at pioglitazone ... I think pioglitazone, particularly in lower doses…is an ideal drug for prevention of diabetes"
• Pioglitazone Use and Risk of Bladder Cancer: Population Based Cohort Study - Medscape, 4/14/16 - "Compared with other antidiabetic drugs, pioglitazone was associated with an increased risk of bladder cancer (121.0 v 88.9 per 100 000 person years; hazard ratio 1.63 ... The absence of an association with rosiglitazone suggests that the increased risk is drug specific and not a class effect"
• Lower CV Risk -- With a Diabetes Drug - Medscape, 4/1/16 - "The IRIS trial showed that over about 5 years, there was a 24% reduction in stroke or myocardial infarction in patients taking pioglitazone. I told him that we can stop the metformin and sitagliptin, add in pioglitazone and empagliflozin, and continue the statin, the blood pressure medications, et cetera" - Speaking of the devil, this is on of the benefits I was thinking about when I wrote the note on the next study below.
• More Evidence This Drug Raises Bladder Cancer Risk - WebMD, 3/30/16 - "When compared with other classes of diabetes drugs, the higher risk of bladder cancer linked to Actos was significant ... The controversy over Actos and Avandia is largely moot at this point, diabetes experts say, because newer and safer medications have supplanted them" - Note:  I'm not sure that what they call "safer medications" have the same benefits as Actos though.
• Diabetes Drugs Have Positive Effect in MS - Medscape, 3/22/16 - "After a mean follow-up of 26.7 months, patients receiving metformin or pioglitazone had a significant decrease in the number of new or enlarging T2 lesions on brain MRI compared with the control group and compared with findings on MRIs performed 2 years before ... This decrease was evident even after 6 months of treatment. The lowest mean number of new or enlarging T2 lesions occurred after 18 months of treatment (metformin, 0.5; pioglitazone, 0.6) and remained low throughout the study ... There was no significant difference between the two treatments ... Although not designed to detect treatment effects, the study did find that fasting glucose levels, fasting insulin levels, insulin resistance, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and systolic blood pressure all declined significantly in both treatment groups after 12 months" - See metformin at The Antiaging Store.
• Diabetes Drug May Help Prevent Second Stroke - WebMD, 2/17/16 - "Along with standard treatment after a stroke -- including blood thinners, and blood pressure and cholesterol medication -- the addition of Actos reduced the odds of another stroke by 24 percent compared to a placebo ... No one knows how Actos works to prevent stroke, Kernan said. The best guess is that the drug reduces inflammation, improves insulin resistance, helps manage fats in the body and "favorably affects the function of blood vessels,""
• Could Common Diabetes Drugs Help Fight Leukemia? - WebMD, 9/2/15 - "patients with chronic myeloid leukemia (CML) who received a glitazone -- a class of drug for type 2 diabetes -- along with the standard CML drug imatinib remained disease-free for up to nearly five years ... Actos and Avandia are two well-known glitazone"
• Examination of use of diabetes drug pioglitazone and risk of bladder cancer - Science Daily, 7/21/15 - "There was no statistically significant increased risk of bladder cancer associated with pioglitazone use. However, a small increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether the observed associations are causal or due to chance, residual confounding, or reverse causality"
• Diabetes drug may protect against Parkinson's disease: A type of drug used to treat diabetes may reduce the risk of developing Parkinson's disease - Science Daily, 7/21/15 - "diabetes patients taking glitazone antidiabetes drugs (either rosiglitazone or pioglitazone) had a 28% lower incidence of Parkinson's disease than people taking other treatments for diabetes who had never taken glitazones ... Glitazones are a class of drug that activate the peroxisome proliferation-activated gamma (PPARγ) receptor, which is found inside cells in many different body organs. PPARγ activation by glitazones leads to reduced insulin resistance, which has been useful for treating people with diabetes, but the receptor has many other functions that have not been studied as thoroughly in humans"
• Diabetes medication reduces dementia risk: Analysis of health insurance data suggests preventive effect - Science Daily, 6/23/15 - "Treatment with pioglitazone showed a remarkable side benefit. It was able to significantly decrease the risk of dementia ... The longer the treatment, the lower the risk ... Risk reduction was most noticeable when the drug was administered for at least two years ... Metformin -- another frequently prescribed antidiabetic drug -- also lowered the risk of developing dementia. However, the effect was lower than that of pioglitazone" - See metformin at The Antiaging Store.  Pioglitazone is harder to find.  I've been taking both in low dose for years for various anti-aging advantages.
• New Study Refutes Pioglitazone and Bladder-Cancer Link - Medscape, 12/3/14 - "I have not seen the 10-year follow-up published yet, but clearly reports that do not find any association with bladder cancer should be reassuring ... Our study combines data across countries — this is useful, as false associations due to bias can sometimes arise because of specific prescribing patterns within a given country. Looking across different [countries] means that one is less likely to jump to erroneous conclusions"
• Diabetes Drug Linked to Lower Dementia Risk - Medscape, 7/24/14 - "they studied the association of pioglitazone and dementia incidence in a prospective cohort study of 145,717 adults age 60 years and older who were free of dementia at baseline in 2004 and followed until 2010. The information on prescriptions of pioglitazone on a quarterly basis was expressed as a linear variable covering the time-dependent number of quarters of prescriptions, which ranged between 0 and 28 quarters ... With each additional quarter of pioglitazone prescription, the relative risk for dementia fell by 6%" - Note:  Pioglitazone is another one I've been taking in low doses for years for anti-aging.
• Dose effect of thiazolidinedione on cancer risk in type 2 diabetes mellitus patients: a six-year population-based cohort study - J Clin Pharm Ther. 2014 Mar 24 - "The adjusted HRs for those prescribed TZD were 0.74 (95% CI 0.43-1.26, P = 0.27), 0.39 (95% CI 0.33-0.45, P < 0.001) and 0.49 (95% CI 0.27-0.89, P = 0.02), respectively, relative to non-DM patients, DM patients prescribed other anti-DM drugs besides TZDs and DM patients not prescribed any anti-DM drugs. In addition, the effects of TZDs were shown to be significantly dose dependent (P for trend < 0.001). The risk of breast, brain, colorectal, ear-nose-throat, kidney, liver, lung, lymphatic, prostate, stomach, and uterus cancer was significantly lower in those prescribed TZDs"
• Dose effect of thiazolidinedione on cancer risk in type 2 diabetes mellitus patients: a six-year population-based cohort study - J Clin Pharm Ther. 2014 Mar 24 - "The adjusted HRs for those prescribed TZD were 0.74 (95% CI 0.43-1.26, P = 0.27), 0.39 (95% CI 0.33-0.45, P < 0.001) and 0.49 (95% CI 0.27-0.89, P = 0.02), respectively, relative to non-DM patients, DM patients prescribed other anti-DM drugs besides TZDs and DM patients not prescribed any anti-DM drugs. In addition, the effects of TZDs were shown to be significantly dose dependent (P for trend < 0.001). The risk of breast, brain, colorectal, ear-nose-throat, kidney, liver, lung, lymphatic, prostate, stomach, and uterus cancer was significantly lower in those prescribed TZDs"
• Actos (pioglitazone hydrochloride) - rxlist.com - "ACTOS improves glycemic control while reducing circulating insulin levels"
• Some Diabetes Drugs May Affect Cancer Risk in Women - WebMD, 12/6/13 - "Cleveland Clinic researchers analyzed data from more than 25,600 women and men with type 2 diabetes ... The drugs included "insulin sensitizers," which lower blood sugar and insulin levels in the body by increasing the muscle, fat and liver's response to insulin. The other drugs analyzed were "insulin secretagogues," which lower blood sugar by stimulating beta cells in the pancreas to make more insulin ... The use of insulin sensitizers in women was associated with a 21 percent decreased cancer risk compared to insulin secretagogues, the investigators found. Furthermore, the use of a specific insulin sensitizer called thiazolidinedione was associated with a 32 percent decreased cancer risk in women compared to sulphonylurea, an insulin secretagogue ... there were no significant differences between men who used insulin sensitizers or secretagogues"
• Pioglitazone Back on Market in India - Medscape, 8/6/13 - "The decision to suspend the manufacture, sale, and distribution of pioglitazone in India, citing concerns over adverse effects, particularly bladder cancer, came out of the blue in June and was widely criticized by doctors and others there. In mid-July, however, a meeting of the drug technical advisory board (DTAB) recommended that pioglitazone be put back on the market ... Now, the Ministry of Health and Family Welfare has announced that all formulations containing pioglitazone for human use are allowed to be manufactured, sold, and distributed once again, albeit with warnings on the package insert"
• India May Soon Revoke Ban on Diabetes Drug Pioglitazone - Medscape, 7/23/13 - "The Indian government's suspension of the diabetes drug pioglitazone may soon be revoked if the government follows the advice of the Drug Technical Advisory Board (DTAB) there. The DTAB met July 19 and recommended that pioglitazone be put back on the market in India, albeit with a boxed warning about bladder cancer ... The Government may or may not accept its advice ... There were accusations in some of the media coverage that the motivation behind this correspondence was the fact that Dr. Mohan had received funding from Merck, Sharpe & Dohme, the Indian subsidiary of Merck & Co, whose newer diabetes drug sitagliptin (Januvia) stands to gain if pioglitazone is unavailable ... The same report adds that another Chennai-based diabetes doctor, Vijayam Balaji, MD, from Dr. Balaji Diabetes Care Centre, evaluated bladder cancer risk in 958 patients receiving pioglitazone but did not find any increased risk across all age groups, even after 2 years of treatment"
• India Suspends Diabetes Drug Pioglitazone - Medscape, 7/8/13 - "The ruling came seemingly out of the blue ... The government could have put some restrictions [on it] but still allowed marketing of the drug because there is no clear-cut indication that it does cause bladder cancer ... there are new data coming, which are probably in favor of pioglitazone, expected in 2014"
• Diabetes Drug Shows Promise in Treatment of Neurodegenerative Disease - Medscape, 6/7/13 - "Pioglitazone halted the nerve fibre degeneration by preventing the loss of mitochondria, and inhibiting metabolic failure and oxidative stress in the treated mice, and hence also halted locomotor disabilities ... Although X-ALD is a relatively rare disease with a minimum incidence of 1 in 17 000 males, there are other neurodegenerative disorders caused by myelin sheath degeneration, for example multiple sclerosis, and many others where impaired bioenergetics combined with oxidative stress and degeneration of axons are known to be involved. The latter category of disease includes Parkinson's, Huntington's, and Alzheimer's ... It is possible that our findings may be relevant to these conditions as well"
• Diabetes drug improves memory, study suggests - Science Daily, 11/21/12 - "treatment with the anti-insulin-resistance drug rosiglitazone enhanced learning and memory as well as normalized insulin resistance. The scientists believe that the drug produced the response by reducing the negative influence of Alzheimer's on the behavior of a key brain-signaling molecule" - Note:  Rosiglitazone is the one that they say increases the risk of heart disease.  Pioglitazone is in the same class of drugs but they claim that increases the chances of bladder cancer.  Personally I don't have diabetes but I take low dose metformin and pioglitazone.  See my Insulin and Aging page.  See pioglitazone at OffshoreRx1.com.
• Pioglitazone Is Associated With Risk for Bladder Cancer - Medscape, 8/7/12 - "Ever use of pioglitazone was associated with 83% higher risk for bladder cancer ����� a significant increase — compared with never users. The bladder cancer rate increased significantly with duration of pioglitazone use, with the highest rates in patients who were exposed for >2 years, and in patients whose cumulative dose exceeded 28,000 mg. Notably, no excess risk for bladder cancer was observed for patients who received rosiglitazone (Avandia)"
• Effect of pioglitazone on testosterone in eugonadal men with type 2 diabetes mellitus: A randomized double blind placebo-controlled study - Clin Endocrinol (Oxf). 2012 Jul 20 - "randomly assigned to receive pioglitazone 30 mg per day or placebo along with existing glimepiride and metformin therapy ... As compared to placebo, six months of pioglitazone therapy in patients with T2DM resulted in significant reduction in mean total testosterone level (16.1 to 14.9 vs 17.1 to 17.0 nmol/L; p = 0.031), calculated free testosterone (p = 0.001) and bioavailable testosterone (p = 0.000) despite significant increase in sex hormone binding globulin (p = 0.000). Plasma androstenedione (∆(4) ) level increased (1.5 to 1.9 ng/ml; p = 0.051) following pioglitazone therapy"
• Brain insulin resistance contributes to cognitive decline in Alzheimer's disease - Science Daily, 3/23/12 - "This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer's disease ... Our research clearly shows that the brain's ability to respond to insulin, which is important for normal brain function, is going offline at some point ... We believe that brain insulin resistance may be an important contributor to the cognitive decline associated with Alzheimer's disease ... The risk of developing Alzheimer's disease is increased by 50 percent in people with diabetes ... insulin resistance of the brain occurs in Alzheimer's disease independent of whether someone has diabetes ... The investigators used samples of postmortem brain tissue from non-diabetics who had died with Alzheimer's disease, stimulated the tissue with insulin, and measured how much the insulin activated various proteins in the insulin-signaling pathways ... three insulin-sensitizing medicines are already approved by the FDA for treatment of diabetes. These drugs readily cross the blood-brain barrier and may have therapeutic potential to correct insulin resistance in Alzheimer's disease and MCI" - Note:  I suspected this for a long time.  It doesn't say what those three drugs are but I'm guessing metformin and Actos are two of them.  I don't have diabetes but I take low doses of both.  My doc says I'm crazy.
• Pioglitazone: A Key Component for Type 2 Diabetes Therapy - Medscape, 10/5/11 - "Even in patients who do not already have known CV disease there is an increasingly strong case developing in favour of using the combination of metformin, pioglitazone and a GLP-1 agonist in the modern management of type 2 diabetes.[42] This case is argued by Professor Ralph DeFronzo who, in print[42] as well as in a webcast,[43] describes an 'ominous octet' of factors combining in the pathophysiology of type 2 diabetes (figure 4). With regard to these eight factors he points out that sulphonylureas only improve insulin secretion and that even this effect is transient. By contrast, GLP-1 agonists impact on five members of the ominous octet, pioglitazone on four and metformin on two, and that the effects of these agents are complementary and some at least are sustained. As a potent insulin sensitiser, pioglitazone reduces hepatic glucose output and increases glucose uptake in muscle. It improves and preserves pancreatic beta-cell function and therefore insulin secretion and it is also a potent inhibitor of lipolysis. At the level of the liver, metformin is a potent insulin sensitiser reducing hepatic gluconeogenesis and in muscle it provides an additive effect to pioglitazone in promoting glucose uptake. GLP-1 analogues increase the incretin effect, increasing insulin secretion, reducing glucagon secretion and hepatic glucose output. Finally GLP-1 agonists act on the brain reducing appetite and promoting weight loss. DeFronzo[42,43] reminds us that even at the stage of impaired glucose tolerance, individuals have lost >80% of their beta-cell function. Therefore he argues that the modern paradigm for the management of type 2 diabetes would involve intensive management at the earliest stages using metformin, pioglitazone and GLP-1 agonists in combination with a view to achieving a target HbA1C <6%.[42,43] It is worth noting in particular that the combination of these agents does not require expensive home glucose monitoring and these agents are not associated with a risk of hypoglycaemia"
• Diabetes Drug Actos May Raise Risk for Bladder Cancer: FDA - US News and World Report - U.S. News & World Report, 6/16/11 - "In one study involving more than 193,000 patients with diabetes, patients taking Actos were on the drug for an average of two years, the FDA said. "Compared to never being exposed to pioglitazone, a duration of pioglitazone therapy longer than 12 months was associated with a 40 percent increase in risk [for bladder cancer]"
• Diabetes drug Actos linked to possible cancer risk - The Boston Globe, 6/10/11 - "The study found about a 22 percent higher risk of bladder cancer in those taking Actos compared with diabetics taking other drugs"
• Pioglitazone to Prevent Progression to Diabetes: Abstract and Introduction - Medscape,5/25/11 - "More placebo recipients (17%) than pioglitazone recipients (5%) progressed to diabetes. Mean glycosylated hemoglobin (HbA1c) levels rose by 0.2% in the placebo group and remained unchanged in the pioglitazone group"
• System in brain -- target of class of diabetes drugs -- linked to weight gain - Science Daily. 5/1/11 - "PPAR-γ is the target of a class of diabetes drugs called TZDs (thiazolidinediones). This class of drugs reduces blood glucose levels but also causes considerable weight gain ... Seeley and his team set out to determine whether or not the brain's PPAR-γ system was responsible for the weight gain associated with TZDs ... by giving TZD drugs in the same manner that people take them, rats gained weight. This was because the drugs activated PPAR-γ in the brain. Thus, weight gain associated with this class of drugs may not be a result of action of PPAR-γ in fat as had been previously thought, but rather a result of a change in activity in parts of the brain known to regulate appetite ... If you artificially turn on PPAR-γ, you can increase food intake in rats ... If you block these receptors in animals on high-fat diets that make animals obese, animals gain less weight ... In the past, says Seeley, people thought that the production of more fat cells in response to TZD drugs was the cause of the resulting weight gain, but he adds, "Just having more fat cells is not enough to make animals or people fatter. Rather you have to eat more calories than you burn and that is exactly what happens when you turn on the brain PPAR-γ system"
• Obesity and Fatty Liver disease - MedicineNet.com - "Doctors also are using medications to treat non alcoholic fatty liver disease. For example, insulin-sensitizing agents, such as the thiazolidinediones, pioglitazone (Actos) and rosiglitazone (Avandia), and metformin (Glucophage) not only help to control blood glucose in patients with diabetes, but they also improve enzyme levels in patients with non alcoholic fatty liver disease"
• Pioglitazone Shows Promise for Oral Cancer Prevention - Medscape, 3/23/11 - "In a phase 2 clinical trial, the thiazolidinedione pioglitazone partially or completely eliminated two thirds of leukoplakia lesions, which can sometimes become cancerous ... Pioglitazone (Actos, Takeda Pharmaceuticals) "works pretty well — better than anything we've seen before ...Leukoplakia lesions, which are usually caused by irritation, appear on the tongue or sometimes on the insides of the cheek. About 17% of the lesions become invasive cancer, and no treatment has been shown to reliably prevent this ... The researchers randomly divided these patients so that 22 patients received pioglitazone 45 mg daily for 12 weeks and 22 patients served as a comparison group ...15 of the 22 patients in the pioglitazone group had a clinical and/or histologic response; they did not detect any change in the comparison group ... In the pioglitazone group, the lesions completely disappeared in 3 patients and partially disappeared in 12 patients, the epithelium completely returned to normal in 1 patient, and the dysplasia or hyperplasia reverted from advanced to early, or from early to normal, in 6 patients ... Because it is a diabetes drug, researchers checked the subjects' glucose levels, but they found no change, apparently because pioglitazone only affects glucose in diabetics"
• Drug prevents Type 2 diabetes in majority of high-risk individuals - Science Daily, 3/23/11 - "A pill taken once a day in the morning prevented type 2 diabetes in more than 70 percent of individuals whose obesity, ethnicity and other markers put them at highest risk for the disease ... The team also noted a 31 percent decrease in the rate of thickening of the carotid artery, the major vessel that supplies blood to the brain ... The 72 percent reduction is the largest decrease in the conversion rate of pre-diabetes to diabetes that has ever been demonstrated by any intervention, be it diet, exercise or medication ... pioglitazone, which is marketed as Actos® ... It is the most efficacious method we have studied to date to delay or prevent the onset of type 2 diabetes ... This particular medication does two things -- improves insulin resistance and improves beta cell function, which are the two core defects of diabetes" - Note:  Like I've said before, my doc says I'm crazy but I've been taking pioglitazone for anti-aging for some time.  Something that’s discerning is when someone asks why I look young and I mention various things and they disagree with it all of it.  Anyway see pioglitazone at OffshoreRx1.com.
• PERISCOPE Analysis Highlights TZD Lipid Effects - Medscape, 1/10/11 - "In that randomized comparison of the thiazolidinedione (TZD) vs glimepiride(Amaryl, Sanofi-Aventis) in patients with diabetes [2], those taking the TZD saw significantly less coronary disease progression as assessed with intravascular ultrasound (IVUS) over 18 months compared with those taking the other drug, a sulfonylurea. They also benefited with steeper declines in fasting insulin and blood glucose levels, glycated hemoglobin (HbA1C), C-reactive protein (CRP), and triglycerides as well as improved HDL-cholesterol levels ... the post hoc analysis "ties nicely" with the 2006 CHICAGOstudy, in which elevations in HDL were the most important predictor of reduced progression of carotid intima-media thickness"
• Molecular 'switch' contributes to cellular aging process: Discovery suggests new treatments for metabolic diseases - Science Daily, 11/30/10 - "in older animals SMRT acts like a "switch," turning off the protective cellular activities of proteins known as peroxisome proliferator-activated receptors (PPARs). PPARs help regulate genes that promote fat burning to maintain lipid (blood fat) balance and reduce oxidative stress. The researchers were able to reduce the negative effects of oxidative stress by giving antioxidants or drugs known to turn the protective activities of PPARs back on ... PPAR drugs have been used to increase insulin sensitivity and lower blood lipid levels ... we believe SMRT is one of the key players that causes age-dependent decline in mitochondrial function by blocking PPAR activity, and we've found a way to boost the body's ability to better handle metabolic and oxidative stress" - Note: There are several PARR receptor activators such as the blood pressure drug telmisartan and the diabetes medication Actos (some doctors have criticized me for years for taking it for anti-aging).  I've started a webpage on PPARs.  When I get a chance I'll search my site and put the articles on it.
• Study compares risk with 2 diabetes drugs - Science Daily, 8/24/10 - "risks of heart disease events and death were no different between patients who took the diabetes drugs rosiglitazone or pioglitazone. In this analysis, approximately 4 percent of patients taking either drug -- sold as Avandia and Actos -- suffered a heart attack, heart failure, both or died over a 33-month period ... Besides its findings that rosiglitazone and pioglitazone have comparable risks, what distinguishes this latest study from other claims-based analyses is its analysis of death records, which include out-of-hospital deaths ... study also followed patients for a longer period of time than some of the earlier research" - So the two drugs have equal risks but what's confusing is how does that 4% risk compare to a placebo?
• Pioglitazone attenuates prostatic enlargement in diet-induced insulin-resistant rats by altering lipid distribution and hyperinsulinemia - Br J Pharmacol. 2010 Aug 19 - "Increased incidence of benign prostatic hyperplasia among insulin-resistant individuals suggest a role for hyperinsulinemia in prostatic enlargement ... High fat diet led to the accumulation of fat in non-adipose tissues, insulin resistance, compensatory hyperinsulinemia and prostatic enlargement in rats. Pioglitazone treatment altered fat distribution, improved insulin-sensitivity and normalized lipid and insulin level in rats on the high-fat diet. The improved metabolic parameters led to decreased cellular proliferation and increased apoptosis in the prostate gland. High-fat diet feeding and pioglitazone treatment did not change plasma testosterone levels. However, significant prostatic atrophy was observed in castrated, rats irrespective of dietary intervention"
• Vitamin E may be new boon for liver disease - MSNBC, 4/28/10 - "In the study published online in the New England Journal of Medicine, 247 adults with advanced fatty liver disease were randomly assigned to take a high dose of vitamin E (800 international units), the diabetes drug Actos or dummy pills for nearly two years ... Biopsies before and after treatment showed that liver function improved in 43 percent of those in the vitamin E group compared with 19 percent in the placebo group ... participants on the diabetes drug Actos also improved, but to a lesser degree and with a drawback: gaining 10 pounds on average, which remained even after they stopped taking the drug" - See Jarrow FamilE (contains all eight members of the vitamin E family, includes Tocomin) at Amazon.com.
• Pioglitazone improves endothelium-dependent vasodilation in hypertensive patients with impaired glucose tolerance in part through a decrease in oxidative stress - Atherosclerosis. 2010 Jan 4 - "Pioglitazone improved endothelial function in hypertensive patients with IGT through an increase in nitric oxide bioavailability by, in part, a decrease in oxidative stress" - Pioglitazone is one that I take to help prevent diabetes and for anti-aging.
• Metformin vs. Sulfonylureas for Diabetes - WebMD, 12/4/09 - "Researchers reported that diabetes patients who used sulfonylureas had a higher risk of death from all causes and a higher risk of heart failure than diabetes patients who used the most widely prescribed diabetes drug, metformin ... Compared with metformin, also known as Glucophage, single-drug treatment with first- and second-generation sulfonylureas was associated with up to a 61% increased risk for death. Users of second-generation sulfonylureas had up to a 30% higher risk for congestive heart failure ... Patients treated with Actos or Avandia did not appear to have a greater risk for heart attacks than those treated with metformin"
• Diabetes Drug Shows Promise In Fighting Lethal Cancer Complication - Science Daily, 9/24/09 - "in an animal study, a diabetes drug that promotes insulin sensitivity slowed the progression of muscle wasting and fat loss, the main consequences of a syndrome called cachexia ... Research suggests that cachexia is responsible for between one-fifth and one-third of all cancer deaths ... These data provide evidence that in mice with colon cancer tumors, insulin resistance may be involved in the development of cachexia rather than occur as a result of cachexia ... Within eight days, the mice with cancer receiving the rosiglitazone showed more sensitivity to insulin than did the mice with tumors that received no medication. The insulin sensitivity of the medicated mice matched that of mice without tumors ... In addition to stopping fat and muscle loss, the rosiglitazone also dramatically reduced two biological markers present when proteins break down, particularly in muscles, and a third marker that indicates cells are eating their own amino acids in an attempt to survive" - Note:  I don't know why they did this study with rosiglitazone.  That's the one that may be connected to heart disease.  Pioglitazone is the same class of drug and is not connected to heart disease.  I take it for anti-aging also.  See my Insulin and Aging page.
• Rosiglitazone Increases Risk of Heart Failure, Death Compared With Pioglitazone - Doctor's Guide, 8/20/09 - "The researchers estimated that, for every 93 patients treated with rosiglitazone rather than pioglitazone, 1 additional cardiovascular event or death would be predicted to occur annually"
• Pioglitazone Slows Progression of Carotid Atherosclerosis - Medscape, 6/9/09 - "A substudy of ACTOS Now, a diabetes prevention trial comparing pioglitazone (Actos, Takeda Pharmaceuticals) with placebo on risk and incidence of diabetes development, showed that active treatment with the thiazolidinedione slowed the rate of progression of carotid artery intima media thickness (CIMT) by 38% during a 3-year study period" - See Pioglitazone at OffshoreRx1.com.
• Efficacy and safety of therapy with metformin plus pioglitazone in the treatment of patients with type 2 diabetes: a double-blind, placebo-controlled, clinical trial - Curr Med Res Opin. 2009 Mar 23 - "Mean HbA(1c) was reduced by 0.67% in patients receiving pioglitazone plus metformin versus an increase of 0.25% in those receiving metformin alone (p < 0.0001). After 8 weeks' treatment and until the end of the study, HbA(1c) was significantly lower with pioglitazone plus metformin and more patients in this group achieved an HbA(1c) < 6.5% (38.6% vs. 8.1%; p < 0.0001). FBG was also reduced by a significantly greater amount in patients receiving pioglitazone plus metformin compared with metformin monotherapy (-20.5 vs. 1.9 mg/dl; p < 0.0001). Combination therapy was associated with significantly increased HDL-cholesterol, total cholesterol, and adiponectin, and significantly decreased levels of fasting insulin, free fatty acids, and homeostasis model assessment insulin resistance (HOMA-R) compared with metformin monotherapy" - See pioglitazone at OffshoreRx1.com.
• Insulin May Protect Mind, Memory - WebMD, 2/2/09 - "lower insulin levels were enhanced by adding Avandia, which increases the body's sensitivity to insulin. Study authors say the discovery that diabetes drugs shield nerve junctions in the brain from memory loss offers new hope for fighting the disease" - Note:  Avandia is the one with increased heart disease.  I've been taking Actos (pioglitazone) for prevention.  See pioglitazone at OffshoreRx1.com.
• Pioglitazone vs glimepiride: Differential effects on vascular endothelial function in patients with type 2 diabetes - Atherosclerosis. 2008 Dec 6 - "In patients with type 2 diabetes already on metformin, addition of pioglitazone as compared to glimepiride, improved endothelial function despite similar glycemic control. The improvement in endothelial function was mainly due to a reduction in insulin resistance"
• Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer's disease mouse model - Biochem Biophys Res Commun. 2008 Dec 22 - "An early down-regulation of GR, not related to elevated plasma corticosterone levels, was found in different hippocampal subfields of the transgenic mice and this decrease was prevented by rosiglitazone. In parallel with behavioural studies, rosiglitazone also normalized GR levels in older animals. This effect may contribute to explain the attenuation of memory decline by PPARgamma activation in an AD mouse model" - Note:  That's another reason I take rosiglitazone's competitor, pioglitazone which has less chance of causing heart problems.
• Popular Class Of Diabetes Drugs Doubles Risk Of Fractures In Women - Science Daily, 12/10/08 - "We knew going into this study that there was an association between thiazolidinediones and fracture risk ... these agents double the risk of fractures in women with type 2 diabetes"
• Diabetes Medications In Same Class Carry Different Risks Of Heart Failure, Death - Science Daily, 12/1/08 - "individuals taking rosiglitazone had a 15 percent higher rate of death and a 13 percent greater risk of heart failure compared with those taking pioglitazone"
• Older patients face higher mortality, CHF hospitalizations with rosiglitazone over pioglitazone - theheart.org, 11/24/08 - "In the study's primary analysis, which assumed that patients were exposed to the drug for just 60 days after the date of their most recently filled prescription (and adjusted for patient characteristics), diabetic patients initially treated with rosiglitazone had a 15% higher mortality rate than patients on pioglitazone. Rates of first hospitalization for congestive heart failure—a known side effect of TZDs—were 13% higher in the rosiglitazone group than in the pioglitazone group. In contrast to recent studies pointing to a risk of ischemic events with rosiglitazone, rates of MI and stroke were no different between the groups"
• Pioglitazone Improves Fatty Liver Disease in Nondiabetics - Medscape, 11/5/08
• Pioglitazone Cuts Risk of Progression to Diabetes - Clinical Psychiatry News, 7/08 - "People with impaired glucose tolerance were 81% less likely to develop type 2 diabetes over a 3-year period if treated with pioglitazone ... Patients were randomized to treatment with placebo or 30 mg/day pioglitazone. If the drug was tolerated after 1 month, the dose could be increased up to 45 mg/day"
• Pioglitazone Prevents Conversion to Diabetes Among Insulin-Resistant Patients - Doctor's Guide, 6/11/08 - "Patients with impaired glucose tolerance treated with pioglitazone were able to stave off conversion to type 2 diabetes by 81% when compared with individuals who received placebo"
• Pioglitazone Reduces Conversion From Impaired Glucose Tolerance to Diabetes - Medscape, 6/8/08 - "There was a weight gain of 3.9 kg in the pioglitazone group vs about 0.8 kg in the placebo group ... Over a mean follow-up of 2.6 years, pioglitazone markedly decreased, by 81%, the conversion rate of IGT to type 2 diabetes. IGT individuals who had the worst level of beta cell function and who were the most insulin resistant were the individuals who were most likely to develop type 2 diabetes, whether they were in the pioglitazone group...or the placebo group. Pioglitazone was quite safe and quite efficacious"
• Pioglitazone Reduces Conversion From Impaired Glucose Tolerance to Diabetes - Medscape, 6/8/08 - "There was a weight gain of 3.9 kg in the pioglitazone group vs about 0.8 kg in the placebo group ... Over a mean follow-up of 2.6 years, pioglitazone markedly decreased, by 81%, the conversion rate of IGT to type 2 diabetes. IGT individuals who had the worst level of beta cell function and who were the most insulin resistant were the individuals who were most likely to develop type 2 diabetes, whether they were in the pioglitazone group...or the placebo group. Pioglitazone was quite safe and quite efficacious"
• Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials - Diabetes Obes Metab. 2008 May 26 - "The use of pioglitazone does not appear to be harmful in terms of cardiovascular events and all-cause deaths"
• Rosiglitazone and pioglitazone similarly improve insulin sensitivity and secretion, glucose tolerance and adipocytokines in type 2 diabetic patients - Diabetes Obes Metab. 2008 May 12 - "Rosiglitazone and pioglitazone have similar beneficial effects on glycaemic control insulin sensitivity, insulin secretion and plasma adipocytokine levels. However, pioglitazone has a more beneficial effect on the plasma lipid profile than rosiglitazone"
• Pioglitazone May Prevent Progression of Atherosclerosis in Patients With Type 2 Diabetes - Doctor's Guide, 4/2/08 - "Two TZD agents are currently on the market -- pioglitazone and rosiglitazone. Both agents reduce inflammatory biomarkers, while pioglitazone also produces elevation of high-density lipoprotein cholesterol (HDL-C) and reduction of triglyceride levels ... Dr. Nissen said the findings of the PERISCOPE study support the conclusion that treatment with pioglitazone can prevent the progression of atherosclerosis in patients with type 2 diabetes during 18 months of treatment. These finding may have important implications for defining the optimal strategy for management of patients with type 2 diabetes and coronary atherosclerosis" - See pioglitazone at OffshoreRx1.com.
• Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: Results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10) - Am Heart J. 2008 Apr;155(4):712-717 - "major adverse cardiovascular events (MACEs) ... At final visit, 257 (9.9%) pioglitazone-treated and 313 (11.9%) placebo-treated patients had a first event that contributed to the MACE1 end point (hazard ratio 0.82, 95% CI 0.70-0.97, P = .0201). There were statistically significant differences in favor of pioglitazone in 5 of the other MACE end points (P < .05) and a trend to benefit in the sixth (P = .052), with hazard ratios of 0.79 to 0.83 ... In patients with advanced type 2 diabetes at high risk for cardiovascular events, pioglitazone treatment resulted in significant risk reductions in MACE composite end points to 3 years"
• Thiazolidinediones May Act Against Psoriasis - Medscape, 3/26/08 - "The adjusted odds ratio for a first time diagnosis of psoriasis in current users of five or more prescriptions for thiazolidinediones was 0.33, as compared to no use. The adjusted odds ratio for metformin was 0.77" - See pioglitazone at OffshoreRx1.com.
• PROactive: Pioglitazone reduced many different definitions of MACE - theheart.org, 3/5/08 - "The main results, reported in 2005, showed a nonsignificant 10% reduction vs placebo in the study's primary end point of all macrovascular events (all-cause mortality, nonfatal MI [including silent infarction], stroke, ACS, cardiac intervention [CABG or PCI], leg revascularization, or amputation above the ankle). The secondary composite end point of all-cause death, MI, and stroke was reduced by a significant 16%. But the authors have previously attracted criticism for focusing on this one secondary end point when the primary end point of the study was not significant ... The main results, reported in 2005, showed a nonsignificant 10% reduction vs placebo in the study's primary end point of all macrovascular events (all-cause mortality, nonfatal MI [including silent infarction], stroke, ACS, cardiac intervention [CABG or PCI], leg revascularization, or amputation above the ankle). The secondary composite end point of all-cause death, MI, and stroke was reduced by a significant 16%. But the authors have previously attracted criticism for focusing on this one secondary end point when the primary end point of the study was not significant ... "Because there was some controversy about our secondary end point, we decided to apply the PROactive data to other definitions of MACE often used in major clinical trials to see whether the results still held irrespective of which components of the MACE end point were included. We found a consistent reduction in events with all definitions with pioglitazone. This shows that we haven't been scrabbling around for one end point that was positive and that whichever MACE end point we used, we would have gotten a similar result.""
• Why Certain Diabetes Drugs Appear To Lower Blood Pressure - Science Daily, 3/4/08 - "Drugs called thiazolidinediones (TDZs), which are used to treat type II diabetes, target and activate PPAR gamma. In addition to controlling blood sugar, these drugs also appear to lower blood pressure ... It appears that when PPAR gamma is activated it initiates a cascade of events that protect the blood vessel ... When we interfere with the PPAR gamma pathway, those protective mechanisms are eliminated and the blood vessel becomes dysfunctional" - I've read all the negative of thiazolidinediones (TDZs) and I still feel the good outweigh the bad.  I take Actos (pioglitazone HCl) to help prevent diabetes among other thing like I feel they will eventually show that it helps prevent advanced glycation end products, a major cause of aging.
• Comparative effects of rosiglitazone and pioglitazone on fasting and postprandial low-density lipoprotein size and subclasses in patients with Type 2 diabetes - Expert Opin Pharmacother. 2008 Feb;9(3):343-9 - "HbA1c, insulin sensitivity (as assessed by the homeostasis model assessment) and LDL size and subclasses did not differ before treatments. Rosiglitazone and pioglitazone resulted in a similar improvement in HbA1c and insulin sensitivity. Fasting total cholesterol increased more after rosiglitazone compared with pioglitazone (p = 0.04), whereas triglycerides decreased after pioglitazone and increased after rosiglitazone ... Pioglitazone was more effective than rosiglitazone in increasing larger LDL concentrations (in both fasting and postprandial status) as well as in reducing levels of atherogenic small, dense particles (in postprandial status only)"
• Clinical trials with thiazolidinediones in subjects with Type 2 diabetes--is pioglitazone any different from rosiglitazone? - Expert Opin Pharmacother. 2008 Feb;9(3):405-20 - "these agents have markedly different effects on lipids. Rosiglitazone increases total, low- and high-density lipoprotein (LDL and HDL) cholesterol, and triglycerides, whereas pioglitazone has no effect on total or LDL cholesterol, increases HDL cholesterol and decreases triglycerides. Both rosiglitazone and pioglitazone decrease inflammatory markers. Furthermore, both rosiglitazone and pioglitazone may cause a small decrease in blood pressure, improve endothelial function and reduce restenosis. Microalbuminuria is also reduced by both rosiglitazone and pioglitazone. Despite the improvements in surrogate end points, there is little clear evidence that either rosiglitazone or pioglitazone cause major improvements in cardiovascular outcomes. Thus, rosiglitazone has no effect or may even increase cardiovascular outcomes, whereas, in high-risk subjects, pioglitazone has a marginal ability to decrease cardiovascular outcomes"
• Why Belly Fat Hurts the Heart - WebMD, 1/29/08 - "Visceral fat brought the most inflammation and the worst atherosclerosis ... After visceral fat transplantation, mice developed less severe atherosclerosis if their chow was laced with the diabetes drug Actos for 10 weeks. But Actos didn't affect atherosclerosis in other mice"
• Thiazolidinediones-improving endothelial function and potential long-term benefits on cardiovascular disease in subjects with type 2 diabetes - J Diabetes Complications. 2008 Jan-Feb;22(1):62-75 - "Insulin-sensitizing agents such as thiazolidinediones have demonstrated a number of clinical benefits, including anti-inflammatory and antithrombotic properties, which may impact on the course of atherosclerosis. Recent studies have demonstrated that thiazolidinediones improve endothelial function in subjects with and without type 2 diabetes"
• Pioglitazone Lowers Cardiovascular Risk in Diabetic Patients with Kidney Disease - Doctor's Guide, 12/12/07
• Diabetes Drug May Up Elderly Deaths - WebMD, 12/11/07 - "Patients taking thiazolidinediones were 29% more likely to die, 40% more likely to have a heart attack, and 60% more likely to develop congestive heart failure than patients taking different types of diabetes drugs"
• Use of Diabetes Medication by Older Adults Linked with Increased Risk of Heart Problems, Death - Doctor's Guide, 12/11/07
• New Diabetes Drugs Bad for Bones - WebMD, 12/3/07 - "The diabetes drug Avandia promotes osteoporosis not only by slowing bone growth but also by speeding up bone loss. Actos, the only other drug in the same class, likely does this as well"
• TZDs May Reduce Lung Cancer Risk - Physician's Weekly, 10/29/07 - "A 33% reduction in lung cancer risk was found among TZD users"
• Rosiglitazone and Pioglitazone Increase Risk of Congestive Heart Failure But Not the Risk of Cardiovascular Death - Doctor's Guide, 10/2/07
• Fresh fuel for the glitazone controversy: New pioglitazone and rosiglitazone meta-analyses - theHeart.org, 9/11/07 - "If one is anticipating that this type of drug would be appropriate, then I think there is now a lot of evidence to suggest that pioglitazone is the preferred drug"
• Pioglitazone Appears to Have Overall Favorable Effect Regarding Risk of Cardiovascular Events - Doctor's Guide, 9/11/07 - "A meta-analysis of previous research suggests that use of pioglitazone, a glycemic control medication for patients with type 2 diabetes, significantly reduces the risk of heart attack, stroke and death, but increases the risk for serious heart failure"
• Diabetes Drugs Increase Risk Of Heart Failure, Research Shows - Science Daily, 7/27/07
• Higher Cancer Prevalence Seen Among Diabetics Taking Thiazolidinediones - Medscape, 7/18/07 - "There was a significant association with rosiglitazone use with an odds ratio of 1.89 (p = 0.02) for malignancy, but not with pioglitazone use (OR = 1.09"
• From Prediabetes to Diabetes to Cardiovascular Complications: Is the Progression Preventable? - Medscape, 5/31/07 - "TZDs have shown considerable promise in preventing or slowing the progression from prediabetes to diabetes and from diabetes to CV complications. Their effects on insulin resistance and myriad intermediates of CVD (eg, lipids, inflammatory cytokines) suggest potential benefits for at-risk patients that may extend beyond improved glucose control"
• The Rosiglitazone Aftermath: Legitimate Concerns or Hype? - Medscape, 5/24/07 - "Haffner added that if the 43% increase in risk shown in the analysis had occurred in the ongoing RECORD study with rosiglitazone, it would have been stopped a year ago. “I think if a proper meta-analysis were done with rosiglitazone, it would probably show some increased risk, but this would not be significant ... the worst-case scenario from these data is that rosiglitazone would elevate risk for MI from 1.4% to 2% ... Nathan believes pioglitazone is a better bet than rosiglitazone, as it does not have the same adverse lipid profile"
• The Effect of Pioglitazone on Recurrent Myocardial Infarction in 2,445 Patients With Type 2 Diabetes and Previous Myocardial Infarction. Results From PROactive (PROactive 05) - Medscape, 4/30/07
• Pioglitazone in Prior MI Patients - Medscape, 4/23/07
• Diabetes drug 'protects arteries' - BBC News, 3/30/07 - "After 72 week, the thickness of the arteries increased by an average of 0.012 millimetres in the glimepiride group ... But among the patients given pioglitazone, average thickness actually fell by 0.001 millimetres ... Pioglitazone patients also recorded lower levels of sugar in their blood, and higher levels of beneficial HDL cholesterol"
• Actos (Pioglitazone) Tablets - Evaluation of Safety Data Showed Increased Incidence of Fractures in Female Patients - Doctor's Guide, 3/9/07 - "Healthcare professionals should consider the risk of fracture when initiating or treating female patients with type 2 diabetes mellitus with pioglitazone-containing products"
• The Role of Metformin and Pioglitazone in Early Combination Treatment - Medscape, 2/6/07 - "Both metformin and pioglitazone have positive effects on cardiovascular risk factors. Pioglitazone may reduce the progression to type 2 diabetes by effects on both pancreatic beta-cell deterioration and insulin resistance"
• Diabetes Drug [Actos® (pioglitazone)] Shows Promise For Preventing Brain Injury From Radiation Therapy - Science Daily, 1/12/07 - "the diabetes drug pioglitazone prevents inflammation. The drug activates a specific type of peroxisome proliferator-activated receptors (PPARs) that control fat and glucose metabolism, and may be involved in inflammation"
• Anti-Inflammatory Effects of Pioglitazone and/or Simvastatin in High Cardiovascular-Risk Patients With Elevated High Sensitivity C-Reactive Protein: The PIOSTAT Study - Medscape, 1/9/07 - "After 12 weeks of treatment, hs-CRP levels were reduced from 3.64 +/-2.42 mg/l to 2.48 +/-1.77 mg/l with pioglitazone monotherapy and from 3.26 +/-2.02 mg/l to 2.81 +/-2.11 mg/l with simvastatin monotherapy (as illustrated in Fig. 1). Combination treatment with pioglitazone and simvastatin resulted in an additive decrease in hs-CRP levels from 3.49 +/-1.97 mg/l to 2.06 +/-1.42 mg/l after 12 weeks"
• Diabetes Drug Actos May Cut Heart Risk - WebMD, 12/5/06 - "Patients taking Actos had less wall thickening of their carotid arteries -- which bring blood through the neck to the brain -- over 18 months"
• Long-term Safety of Pioglitazone vs Glyburide for Type 2 Diabetes - Medscape, 12/1/06 - "Patients with type 2 diabetes mellitus achieve glycemic control safely and effectively with both pioglitazone and glyburide treatment; however, the results of this study suggest that long-term treatment with pioglitazone is superior to glyburide with respect to tolerability. Overall, pioglitazone treatment resulted in sustained glycemic control, fewer patient withdrawals due to lack of efficacy or hypoglycemia, and fewer cardiac events compared with glyburide"
• Diabetes Drug May Treat Fatty Liver - WebMD, 11/30/06 - "during the study, the Actos patients cut their liver fat by 54%; the placebo group had no change in liver fat ... Actos patients also showed a bigger drop in liver inflammation and a greater improvement in insulin response than the placebo group"
• Pioglitazone Treatment Increases Concentrations of Adiponectin in Plasma - Doctor's Guide, 11/16/06 - "Results showed there was a 6.9 mcg/mL mean increase in adiponectin levels in the pioglitazone group while in non-pioglitazone patients it decreased by 0.42 mcg/mL"
• Diabetes drug may cut heart risks - MSNBC, 11/13/06 - "Patients with type 2 diabetes taking the older generic drug, glimepiride, saw their artery thickness rise by .012 millimeters after 72 weeks on the drug, while those on pioglitazone saw their artery wall thickness drop by .001 millimeters ... pioglitazone raised HDL levels, which seem to protect against heart attacks, by about 13 percent in patients after 24 weeks, and sustained that increase over the life of the study"
• Thiazolidinediones, Insulin Resistance And Obesity - Medscape, 11/8/06 - "Several studies indicate, rather than a neutral effect, a significant reduction in visceral adipose tissue with TZD therapy.[72-75] In patients taking metformin, however, there is conflicting evidence, with some studies showing no significant change in visceral fat mass[73] and others showing significant decreases with metformin treatment (Figure 5).[74] Rosiglitazone (but not metformin) is also associated with decreases in hepatic fat, as shown by reductions in the liver:spleen attenuation ratio, and, while both agents reduced plasma FFA, the decrease was only statistically significant in the rosiglitazone group"
• Widely Prescribed Diabetes Drug Falls Short Of Promise, Says New Review - Science Daily, 10/21/06
• Widely Prescribed Diabetes Drug Falls Short of Promise, Says New Review - Doctor's Guide, 10/18/06
• Cochrane: Pioglitazone benefit unclear - Medscape, 10/18/06 - "They found that these studies did not provide convincing evidence that patient-oriented outcomes such as mortality, morbidity, adverse effects, costs, and health-related quality of life are positively influenced by pioglitazone. Metabolic control measured by glycosylated hemoglobin A1c as a surrogate end point did not demonstrate clinically relevant differences from other oral antidiabetic drugs, and the occurrence of edema was significantly raised with pioglitazone ... Metformin should be the first drug of choice"
• 'Diabetes' Treatment Stops Alzheimer's - WebMD, 9/25/06 - "Alzheimer's disease is really "type 3 diabetes" -- that is, a kind of brain diabetes ... The drug de la Monte and colleagues found so useful for rats is very similar to two drugs currently used to treat diabetes: Actos and Avandia. Known as "TZDs" or "glitazones," the drugs make the body's cells more sensitive to insulin"
• Pioglitazone HCl Demonstrates Significant Improvements in Cardiovascular Outcomes for High-Risk Patients with Type 2 Diabetes - Doctor's Guide, 9/14/06 - "Compared to placebo, patients treated with Actos demonstrated statistically significant risk reductions of heart attacks (23%, P =.046), the combined risk of cardiovascular death, nonfatal heart attack or nonfatal stroke (18%, P =.020) and the combined risk of all-cause mortality, nonfatal heart attack, nonfatal stroke or acute coronary syndrome (17%, P =.010)"
• Pioglitazone Reduces Risk of Second Stroke in Diabetic Patients; No Impact Seen on Risk of First Ever Events - Doctor's Guide, 9/5/06
• PROactive: Pioglitazone Reduces Recurrent Stroke in Patients with Diabetes - Medscape, 9/4/06 - "the risk of recurrent stroke was reduced among patients with a history of stroke for those treated with pioglitazone relative to those not treated, from 10% to about 5% in treated patients, a significant reduction ... Biochemical and diabetic changes from baseline showed a greater reduction in HbA1c, systolic and diastolic BP, and triglycerides, even more of an increase in HDL cholesterol and more of a decrease in the LDL/HDL ratio with pioglitazone treatment"
• Diabetes Drug Shows Promise in Treating Alzheimer's - Doctor's Guide, 7/17/06 - "Treatment of high blood sugar may have a scientific connection to memory loss that could, one day, benefit millions of people with Alzheimer's Disease ... The drug, called pioglitazone HCl"
• Diabetes Drug Shows Promise In Treating Alzheimer's - Science Daily, 7/17/06
• Women Gain More Weight Than Men When Taking Thiazolidinedione - Doctor's Guide, 5/3/06 - "Among the 100 consecutive patients treated with thiazolidinediones, 52 gained significant weight. There were more women in the group of weight-gainers compared to the group of non-weight-gainers (63.5% vs. 37.5%, P <.05)"
• Higher Risk Patients Benefit More After Conversion from Pioglitazone to Rosiglitazone - Doctor's Guide, 5/3/06 - "conversion from rosiglitazone to pioglitazone while maintaining statin therapy, improves the lipid profiles in patients with type 2 diabetes"
• Pioglitazone Has Cholesterol Advantages Versus Rosiglitazone in Elderly Diabetics - Doctor's Guide, 5/2/06 - "patients receiving pioglitazone showed improvements from baseline compared with rosiglitazone in TG, HDL-C, as well as LCL-C particle concentration and size ... Although both agents increased HDL-C, the increase achieved with pioglitazone was significantly greater"
• Rosiglitazone and Pioglitazone on Cardiovascular Risk - Medscape, 4/3/06
• Insulin Sensitizers Cut Cognitive Decline in AD - Clinical Psychiatry News, 4/06 - "There is a critical relationship between insulin resistance and key aspects of brain function ... patients taking rosiglitazone performed significantly better than those taking placebo on a delayed memory task (the Buschke Selective Reminding Test)"
• Newer Diabetic Meds Cost More, But Users Have Fewer Hospital Visits - Science Daily, 3/24/06 - "Taking a TZD as instructed was the strongest predictor of a reduced risk of hospitalization and decreased healthcare costs in this group of patients ... Overall, the participants who took a TZD spent an average of $76 to $150 less per month on total healthcare costs"
• Pioglitazone Treatment Reduces Risk of Second Heart Attack in Diabetics - Doctor's Guide, 11/18/05
• ACTOplus met (pioglitazone HCl and metformin HCl) Now Available in U.S. Pharmacies - Doctor's Guide, 11/1/05
• Drug Can Reduce Risk of Death, Heart Attack, and Stroke in Diabetes Patients - Doctor's Guide, 10/7/05
• Actos Effective in Late-Stage Type 2 Diabetes - Doctor's Guide, 10/6/05
• PROactive Study Shows Takeda's Actos (Pioglitazone HCl) Reduces Heart Attacks, Strokes and Deaths - Doctor's Guide, 9/13/05
• ACTOplus Met Approved by the FDA for Type 2 Diabetes - Doctor's Guide, 8/30/05 - "ACTOplus met combines ACTOS (pioglitazone HCl) and metformin, two widely used diabetes medications, in a single tablet"
• Review: Metformin a Top Diabetes Drug - WebMD, 7/19/05 - "Though many of the newer drugs may promote weight gain, metformin has been associated with modest weight losses in people with type 2 diabetes"
• A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia - Medscape, 7/14/05
• Actos (Pioglitazone HCl) Significantly Improved Components of Diabetic Dyslipidemia - Doctor's Guide, 6/29/05 - "triglyceride levels decreased 12.0 percent in the Actos patients, and rose 14.9 percent in the Avandia patients"
• Pioglitazone May Decrease Cardiovascular Risk Factors Independent of Glycemic Control - Medscape, 6/20/05 - "A medication regimen for type 2 diabetes based on pioglitazone is associated with higher HDL cholesterol levels, reduced CRP levels, and improved carotid intima-media thickness, compared with a regimen based on glimepiride. This effect appears independent of glycemic control"
• Diabetes Drugs May Help Fight Inflammation - WebMD, 6/20/05 - "the type 2 diabetes drugs Actos and Avandia may help fight heart disease not only by improving blood sugar but also by battling inflammation ... Carotid artery wall thickness, a measure of arteries that supply the brain and an indicator of heart disease, also improved with Actos"
• Diabetes Drug Actos (pioglitazone HCl) Showed Anti-Inflammatory Effects in Patients with Type 2 Diabetes in a Clinical Study - Doctor's Guide, 6/16/05 - "CRP decreased by 6.98 mg/L compared to 1.55 mg/L for placebo (p= 0.001). IL-6 decreased by 0.78 pg/mL compared to 0.22 pg/ml for placebo"
• Investigative Drug Muraglitazar (Pargluva) Tops Pioglitazone (Actos) for Blood Glucose Lowering and Lipid Control: Presented at ADA - Doctor's Guide, 6/15/05
• Long-Term, First-Line Monotherapy With Pioglitazone Improves Lipid Profiles in Type 2 Diabetics: Presented at ADA - Doctor's Guide, 6/14/05
• Treatment Switch from Rosiglitazone to Pioglitazone Improves Lipid Measures in Type 2 Diabetics with Dyslipidemia: Presented at ADA - Doctor's Guide, 6/14/05
• Pioglitazone Lowers Blood Pressure in Patients With Diabetes - Medscape, 5/20/05 - "mean DBP values were lowered by -3.1mm Hg and SBP values by -6.9mm Hg. In the stage II hypertension group, treatment with pioglitazone lowered mean DBP values by -8.3mm Hg and SBP values by -18.7mm Hg ... an average change of 2mm Hg will alter the incidence of cardiovascular disease by 17% and ischaemic heart disease by 10% ... Improving insulin sensitivity is associated with a decrease in blood pressure" - See pioglitazone at OffshoreRx1.com,
• Diabetes Medication Pioglitazone HCl May Significantly Improve Predictors of Cardiovascular Risk - Doctor's Guide, 5/10/05 - "the diabetes medication pioglitazone HCl reduced carotid artery intima-media thickness (IMT). Patients taking pioglitazone also experienced significant reductions in insulin resistance, C-reactive protein (a marker for inflammation) and blood pressure, all of which contribute to the overall risk for cardiovascular disease"
• Pioglitazone and Metformin Similarly Effective in Reducing HbA1c - Medscape, 12/13/04
• Pioglitazone Associated With Substantial Regression in Carotid Intima-Media Thickness in Diabetic Patients - Doctor's Guide, 11/10/04
• Pioglitazone Plus Sulfonylurea/Metformin Therapy for Type 2 Diabetes Improves Glucose Control with Fewer Hypoglycaemic Episodes than Insulin - Doctor's Guide, 3/1/04
• Repaglinide Plus Pioglitazone Improves Blood Glucose Control in Type 2 Diabetes Better Than Either Agent Alone - Doctor's Guide, 2/23/04
• Repaglinide/Pioglitazone Combination Therapy Appears Safe, Effective for Patients with Type 2 Diabetes - Doctor's Guide, 2/3/04
• Caution Urged With Diabetes Drugs - WebMD, 12/8/03
• Pioglitazone May Help Children With Type 2 Diabetes Mellitus - Doctor's Guide, 10/6/03
• Pioglitazone Improves Cardiovascular Risk Profile of Patients with Type 2 Diabetes - Doctor's Guide, 10/2/03
• Pioglitazone Exerts Antiatherogenic Effect Independent of Antidiabetic Effect - Doctor's Guide, 9/15/03
• Pioglitazone Decreases Dense LDL in Non-Diabetic Hypertensives - Doctor's Guide, 9/15/03
• Caution Urged on Popular Diabetes Drugs - HealthDay, 9/9/03
• Pioglitazone And Rosiglitazone May Cause Heart Failure And Fluid Build-Up - Doctor's Guide, 9/9/03
• Studies Reveal Good News Regarding Liver Safety of Pioglitazone - Doctor's Guide, 5/21/03
• Pioglitazone/Sulfonylurea And Pioglitazone/Metaformin Combinations Both Effective For Reducing Very Low Density Lipoproteins And Free Fatty Acids - Doctor's Guide, 5/21/03
• Pioglitazone Helpful in Diabetes Therapy - Medscape, 5/19/03
• Pioglitazone Improves Insulin Sensitivity Compared To Metformin - Doctor's Guide, 4/22/03
• Rosiglitazone, Pioglitazone Safe for Type 2 Diabetes , But Effect on Lipid Levels Should Be Considered - Doctor's Guide, 12/6/02
• New Study Indicates Pioglitazone HCl/Metformin Combination Therapy Enhances Glycemic Control in Patients With Type 2 Diabetes - Doctor's Guide, 11/7/02 - "Diabetes patients taking the insulin sensitizer pioglitazone HCl in combination with metformin experienced significantly greater improvement in triglyceride levels than patients taking rosiglitazone maleate and metformin"

Abstracts:

• Pioglitazone, SGLT2 inhibitors and their combination for primary prevention of cardiovascular disease and heart failure in type 2 diabetes: real-world evidence from a nationwide cohort database - Diabetes Res Clin Pract 2023 Apr 24 - "Compared with the reference group, the pioglitazone/SGLT2i combination group had a significantly lower risk for MACE (aHR, 0.76, 95% CI 0.66-0.88) and heart failure (aHR 0.67, 95% CI 0.55-0.82). Pioglitazone was associated with a lower risk of MACE (aHR, 0.82, 95% CI 0.71-0.94) and there was no difference in risk of heart failure compared with the reference group. The incidence of heart failure was significantly decreased in the SGLT2i group (aHR 0.7, 95% CI 0.58-0.86)" - See Pioglitazone at ReliableRXPharmacy and empagliflozin inhousepharmacy.vu.
• Pioglitazone reduces cardiovascular events and dementia but increases bone fracture in elderly patients with type 2 diabetes mellitus: a national cohort study - Aging (Albany NY) 2023 Apr 7 - "major advanced cardiovascular events MACCE (2.76% vs. 3.03%, hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.87-0.95), new- diagnosis dementia (1.32% vs. 1.46%, HR: 0.91, 95% CI: 0.84-0.98) but a higher rate of new-diagnosis bone fractures (5.37% vs. 4.47%, HR: 1.24, 95% CI: 1.19-1.28) than the non-pioglitazone group (n = 174,549). In conclusion, using pioglitazone may reduce the risks of MACCE and dementia but increases the probability of bone fractures in the elderly DM population"
• Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke - Neurology 2023 Feb 15 - "Pioglitazone use was associated with a reduced risk of dementia, compared with non-use (adjusted hazard ratio (HR) = 0.84, 95% CI, 0.75-0.95); the risk reduction in dementia was greater among patients with a history of ischemic heart disease or stroke before DM onset (adjusted HR = 0.46, 95% CI, 0.24-0.90, adjust HR = 0.57, 95% CI, 0.38-0.86, respectively). The incidence of stroke was also reduced by pioglitazone use (adjusted HR = 0.81"
• Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA.IT randomised trial - Diabetes Res Clin Pract 2021 Jul 23 - "Non-Alcoholic Fatty Liver Disease (NAFLD) and type 2 diabetes (T2D) share pathophysiological mechanisms and possible therapeutic strategies. We evaluated the effects of 1-year treatment with pioglitazone or sulphonylureas on indirect indices of NAFLD in people with T2D and the role of insulin-resistance and glucotoxicity in determining these effects ... one-year treatment with pioglitazone even at low dosage significantly improved liver steatosis and inflammation, systemic and adipose tissue insulin resistance in patients with T2D. The beneficial effects of pioglitazone on NAFLD were independent of blood glucose control" - See pioglitazone at ReliableRXPharmacy.
• Pioglitazone: inexpensive; very effective at reducing HbA1c ; no evidence of bladder cancer risk; plenty of evidence of cardiovascular benefit - Diabet Med. 2019 Jun 18 - "We were disappointed to see in the recent article by Ripamonti et al., published in Diabetic Medicine (1), that there still are people pursuing a connection between pioglitazone and bladder cancer, despite all of the accumulated evidence that this association is a red herring (2). The possibility of a connection first came about during pre-clinical studies because of an association between pioglitazone and bladder cancer in male, but not female, rats; no such association was observed in other animals (2). Subsequently, a possible connection was raised in the PROActive Study (3)"
• Pioglitazone's beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study - Int J Impot Res. 2018 Aug 2 - "Pio improves erectile function in rats undergoing BCNI via an IGF-1-mediated pathway"
• Effects of pioglitazone on the incidence of dementia in patients with diabetes - J Diabetes Complications. 2017 Jan 20 - "The risk of dementia decreased by 23% in the pioglitazone-treated cohort compared with that in the comparison cohort after adjustment for age, sex, hypertension, and stroke (adjusted hazard ratio [HR], 0.77; 95% confidence interval [CI]=0.62-0.96). In addition, the adjusted HRs (95% CIs) for dementia were 0.50 (0.34-0.75, P=.001) in high-cumulative dose users, 0.53 (0.36-0.77, P<.001) in long-term users, and 0.66 (0.49-0.90, P=.009) in high-mean daily dose users"
• Pioglitazone for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis - Stroke. 2016 Dec 20 - "Use of pioglitazone in stroke patients with insulin resistance, prediabetes, and diabetes mellitus was associated with lower risk of recurrent stroke (hazard ratio 0.68; 95% confidence interval, 0.50-0.92; P=0.01) and future major vascular events (hazard ratio 0.75"
• Pioglitazone Prevents Diabetes in Insulin-Resistant Patients With Cerebrovascular Disease - Diabetes Care. 2016 Jul 27 - "Among insulin-resistant but nondiabetic patients with a recent ischemic stroke or TIA, pioglitazone decreased the risk of diabetes while also reducing the risk of subsequent ischemic events. Pioglitazone is the first medication shown to prevent both progression to diabetes and major cardiovascular events as prespecified outcomes in a single trial"
• Pioglitazone (Actos) and bladder cancer: legal system triumphs over the evidence - J Diabetes Complications. 2016 Apr 11 - "In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients ... Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine"
• Pioglitazone: No Longer a Worry for Bladder Cancer? - Urology. 2016 Feb 15 - "These results were confirmed in a case control analysis, in which pioglitazone use was observed in19.6% of case patients and 17.5% of controls (adjusted odds ratio, 1.18; 95% CI 0.78-1.80). Analysis of the additional 10 cancers found no association for 8 of them. However, pioglitazone use was, in adjusted analyses, associated with an increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26), as well as an increased risk of pancreatic cancer (HR 1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100 000 person-years, respectively. In this study no association was found between time since initiation, duration or dose of pioglitazone and risk of cancer. Furthermore no statistically significant increased risk of bladder cancer was demonstrated with pioglitazone use"
• Pharmacodynamic Effects of Low-Dose Pioglitazone in Patients with the Metabolic Syndrome without Diabetes Mellitus - Pharmacotherapy. 2016 Jan 29 - "Patients were randomly assigned to receive oral pioglitazone 7.5 mg daily or matching placebo for 8 weeks ... high-molecular-weight (HMW) adiponectin ... Pioglitazone was associated with a significant increase in plasma HMW adiponectin level from baseline to week 8 compared with placebo (+47% vs -10%, p<0.001). Insulin sensitivity increased significantly from baseline to week 8 in the pioglitazone group (+88%, p=0.02) but not in the placebo group (+15%, p=0.14)" - Note:  I've been taking pioglitazone for years for anti-aging.
• Pioglitazone Enhances Survival and Regeneration of Pelvic Ganglion Neurons after Cavernosal Nerve Injury - Urology. 2016 Jan 6 - "bilateral cavernosal nerve crush injury (BCNI) ... Pioglitazone provides a protective effect on pelvic ganglion neurons after BCNI" - Note:  I threw in this study because pioglitazone is something I've been taking for years for anti-aging.
  • Pelvic splanchnic nerves - "From there, they contribute to the innervation of the pelvic and genital organs. The nerves regulate the emptying of the urinary bladder, control opening and closing of the internal urethral sphincter, influence motility in the rectum as well as sexual functions like erection"
  • Difference Between Nerve and Neuron - "nerves are actually projections of neurons"
• Pioglitazone treatment and cardiovascular event and death in subjects with type 2 diabetes without established cardiovascular disease (JDDM 36) - Diabetes Res Clin Pract. 2015 Jul 16 - "Baseline use of pioglitazone (n=493) did not show a statistically protective effect on the primary endpoint (n=175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone"
• Atherosclerosis following renal injury is ameliorated by pioglitazone and losartan via macrophage phenotype - Atherosclerosis. 2015 Jul 4 - "Combination of pioglitazone and losartan is more effective in reducing renal injury-induced atherosclerosis than either treatment alone. This benefit reflects mitigation in macrophage cytokine production, enhanced apoptosis, and a shift toward an anti-inflammatory phenotype"
• Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit - Diabet Med. 2014 Dec 3 - "1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity"
• Efficacy of pioglitazone on erectile function recovery in a rat model of cavernous nerve injury - Urology. 2014 Nov;84(5):1122-7 - "Twenty adult rats were divided into 4 groups: (a) sham, (b) control-bilateral cavernosal nerve crush injury (BCNI), (c) BCNI + low-dose pioglitazone (PioL), and (d) BCNI + high-dose pioglitazone (PioH) ... Pioglitazone improves erectile function in rats undergoing BCNI via a nitric oxide-mediated pathway"
• Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes - Diabetes Obes Metab. 2014 Sep 8 - "Pioglitazone treatment restored in vivo muscle oxidative capacity in diabetic rats to the level of lean controls ... Diminished in vivo muscle oxidative capacity in diabetic rats results from mitochondrial lipid overload and can be alleviated by redirecting the lipids from the muscle into adipose tissue using pioglitazone treatment"
• The effect of pioglitazone and extended-release niacin on HDL-cholesterol in diabetes patients in a real-world setting - Int J Clin Pract. 2013 Nov;67(11):1151-8 - "Patients with type 2 diabetes and hyperlipidemia were included for review if they received the combination of pioglitazone at doses ≥ 15 mg/day and extended-release niacin (Niaspan) at doses ≥ 1000 mg/day for ≥6 months ... a statistically significant increase in HDL-C (+ 25.13%, p < 0.0001) was observed at the conclusion of combination therapy. The HDL-C levels progressively increased with duration of combination treatment, and were not correlated with concomitant statin use. Significant decreases in total cholesterol and triglycerides were detected, and HbA1c decreased 0.84% during combination therapy for all therapies combined" - See niacin at Amazon.com.
• Effects of Pioglitazone on Bone in Postmenopausal Women With Impaired Fasting Glucose or Impaired Glucose Tolerance: A Randomized, Double-Blind, Placebo-Controlled Study - J Clin Endocrinol Metab. 2013 Sep 20 - "Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone ... Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study ... The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up ... Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance"
• Effects of pioglitazone on visceral fat metabolic activity in impaired glucose tolerance or type 2 diabetes mellitus - J Clin Endocrinol Metab. 2013 Sep 12 - "using 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging ... These patients were randomized to treatment with either pioglitazone or glimepiride for 16 weeks ... The metabolic activity of the visceral fat tissues as assessed by FDG uptake was expressed as a target-to-background ratio (TBR) of blood-normalized standardized uptake value ... Pioglitazone significantly decreased the visceral fat volume (130.5+/-53.0 to 122.1+/-51.0 cm2, P=0.013) and TBR values (0.57+/-0.16 to 0.50+/-0.11, P=0.007); glimepiride did not influence visceral fat volume or TBR values. Neither pioglitazone nor glimepiride treatment showed any effect on the volume or TBR values of subcutaneous fat. After 16-week treatment with pioglitazone reduction in visceral fat TBR was correlated to increase in HDL cholesterol levels"
• Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary syndrome: Effects of pioglitazone and metformin treatment - Metabolism. 2013 Aug 16 - "PCOS may represent a state of elevated sensitivity of inflammatory cells in skeletal muscle to cytokines and chemokines, a property that could be reversed by pioglitazone treatment together with improved insulin action"
• Insulin sensitizers and Serum Testosterone in men - Clin Endocrinol (Oxf). 2013 Apr 9 - "The effect of insulin resistance on the hypothalamo-pituitary-gonadal axis is sexually dimorphic1 . In women, it is associated with increased androgen production2 and, in men, usually with hypogonadism3 . Treatment with insulin sensitizers like metformin and pioglitazone in women lead to a decrease in serum total testosterone, while in men with T2DM, metformin therapy has been shown to decrease serum total testosterone4 . However, no data are available regarding the effect of pioglitazone on androgen profile in men"
• Effect of Pioglitazone Versus Metformin on Cardiovascular Risk Markers in Type 2 Diabetes - Adv Ther. 2013 Jan 22 - "The primary objective of this study was to evaluate the effect on C-reactive protein (CRP) after a 16-week treatment period with either pioglitazone or metformin ... Pioglitazone treated patients were found to have statistically significantly larger decreases in mean CRP levels (-0.4 mg/dL) compared to those treated with metformin (-0.2 mg/dL) (P = 0.04), as well as greater reductions in levels of mean fasting plasma glucose (-27 vs. -9 mg/dL; P = 0.01), serum insulin (-2 vs. -1.9 mU/L; P = 0.014), homeostatic model assessment (HOMA) (-1.2 vs. -0.9; P = 0.015), and E-selectin (-12.4 vs. +3.4 μg/mL; P = 0.01). Mean glycated hemoglobin (HbA(1c)) levels decreased in both treatment groups from baseline to week 16 (-0.4% in the pioglitazone group, -0.2% in the metformin group; P = 0.36). Pioglitazone treatment was also found to be associated with a statistically significant increase in total cholesterol levels (+10 mg/dL in the pioglitazone arm, -3 mg/dL in the metformin arm; P = 0.05) and a decrease in liver enzyme levels" - See pioglitazone at OffshoreRx1.com.
• Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies - Diabet Med. 2013 Jan 28 - "Six studies involving 215 142 patients using pioglitazone were included, with a median period of follow-up of 44 months. The hazard of developing bladder cancer was significantly higher in patients using pioglitazone (hazard ratio 1.23; 95% CI 1.09-1.39; I(2) = 0%) compared with control groups. The risk of bias was moderate across the six studies. Considering an incidence rate of 20.8 per 100 000 person years, the number needed to harm was five additional cases of bladder cancer per 100 000 person years"
• Resistance Training and Pioglitazone Lead to Improvements in Muscle Power During Voluntary Weight Loss in Older Adults - J Gerontol A Biol Sci Med Sci. 2013 Jan 4 - "Participants (N = 88; age = 70.6 +/- 3.6 years; body mass index = 32.8 +/- 4.5kg/m(2)) were randomly assigned to one of four intervention groups: pioglitazone or placebo and resistance training (RT) or no RT, while undergoing intentional weight loss via a hypocaloric diet ... In older overweight and obese adults, a hypocaloric weight loss intervention led to significant declines in lean body mass and appendicular lean body mass. However, in women assigned to RT, leg power significantly improved following the intervention, and muscle strength or power was not adversely effected in the other groups. Pioglitazone potentiated the effect of RT on muscle power in women but not in men; mechanisms underlying this sex effect remain to be determined"
• Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes - Diabetes Res Clin Pract. 2012 Dec 7 - "Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72])"
• What Next after Metformin? A Retrospective Evaluation of the Outcome of Second-Line, Glucose-Lowering Therapies in People with Type 2 Diabetes - J Clin Endocrinol Metab. 2012 Oct 17 - "Sulfonylurea monotherapy had significantly higher hazard ratios (HRs) for all-cause mortality (HR 1.459, 1.207-1.763); MACE (HR 1.578, 1.187-2.099); stroke (HR 1.444, 1.050-1.987); and the combined end point (HR 1.381, 1.194-1.597). Metformin plus pioglitazone had significantly lower adjusted HRs for all-cause mortality (HR 0.707, 0.515-0.970) and the combined end point (HR 0.747, 0.612-0.911)"
• Association Between Longer Therapy With Thiazolidinediones and Risk of Bladder Cancer: A Cohort Study - J Natl Cancer Inst. 2012 Aug 9 - "Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk ... Long-term TZD therapy (≥5 years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be common to all TZDs"
• Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis - CMAJ. 2012 Jul 3 - "The limited evidence available supports the hypothesis that thiazolidinediones, particularly pioglitazone, are associated with an increased risk of bladder cancer among adults with type 2 diabetes"
• The effect of pioglitazone treatment on 15-epi-lipoxin A(4) levels in patients with type 2 diabetes - Atherosclerosis. 2012 May 7 - "Arachidonic acid-derived eicosanoids (lipoxins and 15-epilipoxins) have a major role in resolution of inflammation. 15-epi-lipoxin A(4) (15-epi-LXA(4)) is a lipid mediator with strong anti-inflammatory and inflammation-resolving effects ... PIO 15 increased plasma 15-epi-LXA(4) levels (0.63 +/- 0.06-1.05 +/- 0.08 ng/mL, p < 0.01) and adiponectin levels (6.4 +/- 0.3-10.1 +/- 0.7 μg/mL, p < 0.001) and decreased fasting plasma glucose (125 +/- 8-106 +/- 9 mg/dL, p < 0.05), free fatty acids (FFA) (414 +/- 46-320 +/- 38 μmol/l, p < 0.05) and HOMA-IR (5.3 +/- 0.4 to 4.0 +/- 0.4, p < 0.05). Body weight (Δ = 0.2 kg) and HbA1c (7.4 +/- 0.2-7.1 +/- 0.2%) did not change significantly. PIO 30 treated patients had similar increase in plasma 15-epi-LXA(4) (0.64 +/- 0.10-1.08 +/- 0.09 ng/mL, p < 0.01), and decrease in plasma FFA (423 +/- 42-317 +/- 40 μmol/l, p < 0.05) despite a greater increase in plasma adiponectin (6.5 +/- 0.4-15.5 +/- 0.7 ug/mL, p < 0.001) and a greater reduction in HbA1c (8.7 +/- 0.5-7.4 +/- 0.3%, p < 0.01), FPG (159 +/- 16-120 +/- 10 mg/dL, p < 0.01), and HOMA-IR (6.6 +/- 0.8-4.4 +/- 0.4, p < 0.005). Furthermore, PIO 30 treated patients had a significant increase in body weight (Δ = 1.7 kg, p < 0.02)"
• The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study - BMJ. 2012 May 30;344:e3645 - "Overall, ever use of pioglitazone was associated with an increased rate of bladder cancer (rate ratio 1.83, 95% confidence interval 1.10 to 3.05). The rate increased as a function of duration of use, with the highest rate observed in patients exposed for more than 24 months (1.99, 1.14 to 3.45) and in those with a cumulative dosage greater than 28 000 mg (2.54, 1.05 to 6.14)"
• A randomized placebo controlled double blind crossover study of pioglitazone on left ventricular diastolic function in type 2 diabetes - Int J Cardiol. 2012 Apr 21 - "Tissue Doppler early peak velocity (e'), a measure of LV diastolic function, was the primary outcome. Pioglitazone significantly increased e' by 0.7(0.1, 1.3) cm/s (mean (95% confidence interval); p=0.02) compared with placebo. Pioglitazone also increased E/A and mitral deceleration index, ejection fraction, stroke volume and weight, whereas fasting glucose, HbA1c, total peripheral resistance and LV meridional end systolic stress were decreased ... Treatment with pioglitazone for 12weeks improves left ventricular diastolic and systolic function in people with type 2 diabetes"
• Pioglitazone in acromegaly - an open-label, prospective study - Clin Endocrinol (Oxf). 2012 Apr 18
• Pioglitazone treatment increases COX-2 derived PGI(2) production and reduces oxidative stress in hypertensive rats. Role on vascular function - Br J Pharmacol. 2012 Jan 5 - "PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated to gene transcription interference. This study analyzes if chronic treatment with pioglitazone of adult spontaneously hypertensive rats (SHR) alters blood pressure and vascular structure and function, and the possible mechanisms involved Experimental approach ... Pioglitazone treatment, although did not reduce blood pressure in SHR, increased COX-2-derived PGI(2) production, reduced oxidative stress, and increased NO bioavailability, all of them involved on vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies"
• Pioglitazone and Bladder Cancer: A population-based study of Taiwanese - Diabetes Care. 2011 Dec 30 - "The association between pioglitazone and bladder cancer was not significant. However, confirmation of this finding is required because of the possible lack of statistical power owing to the small number of events"
• Pioglitazone may accelerate disease course of slowly progressive type 1 diabetes - Diabetes Metab Res Rev. 2011 Nov;27(8):951-3 - "The enrolled SPIDDM patients were randomly allocated to a pioglitazone or metformin group. When the haemoglobin A1C level was more than 8% on two consecutive occasions, the case was considered to reach the end point ... By 4 years post-intervention, all patients had reached the end point in the pioglitazone group, whereas only 20% of patients had reached the end point in the metformin group"
• Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ABCG1 expressions via PPARγ/LXRα pathway: Findings from in vitro and ex vivo studies - Atherosclerosis. 2011 Aug 4 - "Pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, reportedly reduces cardiovascular events in diabetic patients ... Pioglitazone enhanced ChE from macrophages by increasing ABCA1/G1 in LXR-dependent and -independent manners. Our comparable in vitro and ex vivo results shed new light on pioglitazone's novel anti-atherogenic property" - See pioglitazone at OffshoreRx1.com.
• Pioglitazone induces regression and stabilization of coronary atherosclerotic plaques in patients with impaired glucose tolerance - Diabet Med. 2011 Sep 26 - "Compared with the control group, 6 months' treatment with pioglitazone significantly decreased coronary plaque burden (50.7 +/- 11.1 vs. 64.1 +/- 10.3%, P < 0.05), plaque area (6.22 +/- 2.03 vs. 8.31 +/- 4.29, P < 0.05), thin-cap fibroatheroma prevalence (11 vs. 22%, P < 0.05) and percentage of necrotic core area (16 +/- 8 vs. 31 +/- 7%, P < 0.05). Compared with the control group, serum high-sensitivity C-reactive protein and plasma endothelin-1 levels were significantly lower and adiponectin level significantly higher in patients in the pioglitazone group. Serum adiponectin level was negatively correlated with plasma endothelin-1 level and coronary plaque area (r = 0.739 and -0.431, respectively, both P < 0.05). Conclusions:  Pioglitazone may induce regression and stabilization of coronary atherosclerotic plaques. The mechanisms might involve inhibition of inflammation, increase in adiponectin level and improvement in endothelial function"
• Thiazolidenediones induce tumour-cell apoptosis through the Akt-GSK3β pathway - J Clin Pharm Ther. 2011 Mar 16 - "Prostate cancer is a major health threat for men. Thiazolidenediones (TZDs) are synthetic ligands of the peroxisome proliferator-activated receptor γ (PPARγ), and previous studies have shown that TZDs induce apoptosis of prostate cancer cells independently of PPARγ activation. However, the exact mechanism of these effects remains unknown ... The apoptosis-inducing effect of TZDs on prostate cancer cells involves the inhibition of Akt phosphorylation. Furthermore, TZDs induce inactivation of GSK3β, a multifunctional kinase that mediates essential events promoting prostate cancer development and acquisition of androgen independence. In addition, the GSK3β inhibitor lithium chloride sensitizes prostate cancer cells to TZDs cytotoxicity. What is new and Conclusion:  Our data suggest that modulation of Akt-GSK3β pathway is involved in the cell death pathway engaged by TZDs in prostate cancer cells. This reveals another possible mechanism of TZDs on apoptosis in prostate cancer. Inhibition of the Akt-GSK3β cascade may be a useful approach in prostate cancer" - Got that because I'm going to give a test on it in next weeks newsletter.  The point is that TZDs such as pioglitazone may help prevent or slow prostate cancer.
• Pioglitazone activates aortic telomerase and prevents stress-induced endothelial apoptosis - Atherosclerosis. 2011 Feb 17 - "Telomeres and associated proteins are regulators of cellular survival, regeneration and aging. PPAR-γ agonists may mediate vascular effects in addition to insulin sensitizing. We therefore examined whether pioglitazone regulates vascular telomere biology ... C57/Bl6 mice were randomized to treatment with pioglitazone (20mg/kg i.p. daily) or vehicle for 4 weeks (n=6-8 per group). Telomere repeat amplification protocols showed a 2-fold increase of aortic telomerase activity in the pioglitazone group. Telomere repeat-binding factor 2 protein and mRNA levels (236%+172% of vehicle) as well as phosphorylation of protein kinase Akt (479% of vehicle) were up-regulated. Western blots demonstrated reduced aortic expression of senescence markers p16, cell-cycle checkpoint kinase 2 and p53. These regulatory mechanisms were independent of acute changes of telomere length. Similar observations were made in mononuclear cells (MNC) from these mice and in cultivated bovine aortic endothelial cells, human MNC and endothelial progenitor cells (EPC). Telomerase activation by pioglitazone in cultivated cells was prevented by Akt inhibitors. To test the functional relevance of the findings, isolated mononuclear cells (MNC) were exposed to H(2)O(2). MNC from pioglitazone-treated mice exhibited reduced apoptosis (AnnexinV-FACS). In vivo, lipopolysaccharide-induced aortic endothelial apoptosis was potently prevented in pioglitazone-treated animals (hairpin oligonucleotide assay). Both, up-regulation of telomere-regulating proteins and prevention of oxidative stress-induced aortic apoptosis, were absent in telomerase reverse transcriptase (TERT)-deficient mice ... The findings underscore the important role of telomere-regulating proteins for vascular cell function and survival" - Note:  My doctor says I'm crazy but I've been taking pioglitazone for anti-aging for years.
• Pioglitazone improves endothelial and adipose tissue dysfunction in pre-diabetic CAD subjects - Atherosclerosis. 2010 Dec 28 - "Pioglitazone significantly improves endothelial and adipose tissue dysfunction in pre-diabetic patients with CAD"
• Effects of pioglitazone vs metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes - a randomized controlled trial - Diabetes Obes Metab. 2011 Jan 21 - "Participants assigned to pioglitazone gained more weight and experienced greater improvements in some coronary risk measures (HDL-cholesterol, triglycerides, adiponectin, and C-reactive protein) than did those assigned to metformin. Conclusion: Compared with metformin, pioglitazone treatment improved the imbalance between endothelial damage and repair capacity, and led to more favorable changes in coronary risk factors in patients with newly-diagnosed type 2 diabetes"
• Thiazolidinediones and congestive heart failure in veterans with type 2 diabetes - Diabetes Obes Metab. 2010 Dec 6 - "The incidence of CHF was higher in patients who were not treated with TZDs than in those who received TZDs. After adjustment for multiple cardiac risk factors, the hazard ratio for development of CHF for TZD versus non-TZD treated patients was 0.69 with a 95% confidence interval of 0.60 to 0.79"
• Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes - J Clin Hypertens (Greenwich). 2010 Dec;12(12):973-82 - "fixed-dose combination (FDC) of pioglitazone/metformin compared with the respective monotherapies ... FDC and pioglitazone increased high-density lipoprotein cholesterol by 14.20% and 9.88%, respectively, vs an increase of 6.09% with metformin (P<.05, metformin vs FDC). Triglycerides decreased with all three treatments -5.95%, -5.54% and -1.78%, respectively; P=not significant). FDC and pioglitazone significantly decreased small low-density lipoprotein and increased large low-density lipoprotein particle concentrations. Reductions in high-sensitivity C-reactive protein were greater in the FDC and pioglitazone groups. Increases in adiponectin were significant in the FDC and pioglitazone groups (P<.0001 vs metformin). Overall, adverse events were not higher with the FDC. Thus, treatment with the FDC resulted in improved levels of CV biomarkers, which were better than or equal to monotherapy"
• Synergistic effects of ascorbic acid and thiazolidinedione on secretion of high molecular weight adiponectin from human adipocytes - Diabetes Obes Metab. 2010 Dec;12(12):1084-9 - "AA supplementation significantly increased secretion of HMW adiponectin (1.7-fold) without altering adiponectin expression or total adiponectin secretion. TZD significantly increased expression (3-fold) and secretion of total (1.4-fold) but not HMW adiponectin. Combined supplementation resulted in a significant increase in expression (3-fold) and secretion of total (1.8-fold) and HMW (5-fold) adiponectin. Similar results were seen in cells co-treated with TNFα" - See my adiponectin page.  High adiponectin is a good thing.  Actos (pioglitazone) is a TZD and is something I've been taking for anti-aging for some time.  Not only does it increase adiponectin but it increases insulin sensitivity.  See my Insulin and Aging page.  See pioglitazone at OffshoreRx1.com.
• Fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment - Metabolism. 2010 Jan 19 - "high-sensitivity C-reactive protein (hsCRP) ... Pioglitazone treatment for 12 weeks decreased serum hsCRP levels (0.83 [1.14] to 0.52 [0.82] mg/L, P < .001) and improved glycemic control (fasting glucose, P < .001; glycosylated hemoglobin, P < .001) and lipid profiles (triglyceride, P = .016; high-density lipoprotein cholesterol, P < .001). Between responders and nonresponders to the hsCRP-lowering effect of pioglitazone, there were significant differences in baseline hsCRP levels and changes in the postprandial glucose and the ratio of visceral fat thickness (VFT) to subcutaneous fat thickness (SFT) (P = .004, .011, and .001, respectively). The percentage change in hsCRP levels after treatment was inversely correlated with baseline hsCRP levels (r = -0.497, P < .001) and directly correlated with the change in postprandial glucose (r = 0.251, P = .021), VFT (r = 0.246, P = .030), and VFT/SFT ratio (r = 0.276, P = .015). Logistic regression analysis revealed that the hsCRP-lowering effect of pioglitazone was affected by baseline hsCRP levels (odds ratio [OR] = 7.929, P = .007) as well as changes in postprandial 2-hour glucose (OR = 0.716, P = .025) and VFT/SFT ratio (OR = 0.055, P = .009). In conclusion, treatment with pioglitazone produced an anti-inflammatory effect, decreasing serum hsCRP levels; and a decrease in the VFT/SFT ratio was independently and most strongly associated with the hsCRP-decreasing effect. These results suggest that abdominal fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment"
• Pioglitazone Reduces ER Stress in the Liver: Direct Monitoring of in vivo ER Stress Using ER Stress-activated Indicator Transgenic Mice - Endocr J. 2009 Sep 29 - "8 weeks of pioglitazone treatment reduced the accumulation of fat droplets in the liver and attenuated the development of insulin resistance. In the liver of the ERAI transgenic mice, ERAI fluorescence activity was clearly reduced as early as after 4 weeks of pioglitazone treatment, preceding the improvement of insulin resistance. In addition, after the pioglitazone treatment, serum free fatty acid and triglyceride levels were decreased, and serum adiponectin levels were increased. These data indicate that pioglitazone treatment suppresses ER stress in the liver which may explain, at least in part, the pharmacological effects of pioglitazone to reduce insulin resistance"
• Improving cardiovascular risk--applying evidence-based medicine to glucose-lowering therapy with thiazolidinediones in patients with type 2 diabetes - Int J Clin Pract. 2009 Sep;63(9):1354-68 - "Pioglitazone is the preferred thiazolidinedione to reduce cardiovascular risk in people with type 2 diabetes"
• Liver Safety in Patients with Type 2 Diabetes Treated with Pioglitazone: Results from a 3-Year, Randomized, Comparator-Controlled Study in the US - Drug Saf. 2009;32(9):787-800 - "No case of hepatic dysfunction or hepatic failure was reported in either treatment group; two cases of hepatic cirrhosis with glibenclamide were reported. This study demonstrates an hepatic safety profile of pioglitazone similar to that of glibenclamide in long-term use in patients with poorly controlled type 2 diabetes"
• Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus independent of weight changes - J Diabetes Complications. 2009 Jul 3 - "metformin (Met) ... Pio plus the American Diabetes Association diet (Pio+ADA) ... Pio plus a portion control weight loss diet (Pio+PC) ... The Pio+ADA group gained (mean+/-S.E.M.) 2.15+/-1.09 kg, while Pio+PC and Met+ADA group lost -2.59+/-1.25 and -3.21+/-0.7 kg, respectively. Pio-treated groups (Pio+ADA and Pio+PC) significantly decreased hepatic fat as indicated by increased liver density on CT scan [10.1+/-2.4: 11.4+/-1.0 Hounsfield units (HU)], compared with Met+ADA group (-2.4+/-3.1 HU). The Pio groups demonstrated significantly increased serum adiponectin, (8.6+/-1.5; 7.4+/-1.6 mug/ml) independent of weight change, compared to Met+ADA (-0.14+/-0.6 mugm/ml) group which lost weight. Serum hs-CRP decreased in groups showing weight loss (Pio+PC, -3.1+/-1.7 mg/l; Met+ADA, -1.5+/-1.2 mg/l) compared to Pio+ADA (1.8+/-3.0 mg/l) group that gained weight" - Note:  This is just one of the many reasons I take pioglitazone even though I don't have diabetes.
• Low-dose pioglitazone increases serum high molecular weight adiponectin and improves glycemic control in Japanese patients with poorly controlled type 2 diabetes - Diabetes Res Clin Pract. 2009 Jun 20 - "7.5mg/day of pioglitazone ... adiponectin increased markedly from 5.2 (2.4, 8.6)mug/ml at baseline to 9.8 (4.1, 12.6)mug/ml"
• Pioglitazone might prevent the progression of slowly progressive type 1 diabetes - Intern Med. 2009;48(12):1037-9 - "We report a slowly progressive type 1 diabetic patient whose insulin production was preserved for 4 years (SigmaC-peptide from 29.48 ng/mL to 24.58 ng/mL) using pioglitazone despite a high titer of anti-GAD antibody (GADA; 120.7 U/mL). This case suggests that pioglitazone might prevent or delay the loss of insulin secretion and insulin dependency in slowly progressive type 1 diabetic patients" - See pioglitazone at OffshoreRx1.com.
• Pioglitazone Improves Endothelial Function with Increased Adiponectin and High-density Lipoprotein Cholesterol Levels in Type 2 Diabetes - Endocr J. 2009 Jun 9 - "After treatment, HbA1c levels equally decreased in both groups, but PIO-treated group had significantly increased high-density lipoprotein cholesterol (HDL-C) levels, and decreased triglyceride, fasting insulin levels and HOMA-R. After treatment, increases in %FMD, plasma HDL-C and adiponectin (APN) levels were significantly greater in PIO-treated group than those in control group. Changes of %FMD showed significant positive correlations with those of plasma APN and HDL-C levels. In conclusion, the present study showed that treatment of T2DM improved endothelial function with greater increases in %FMD, APN and HDL-C levels in PIO-treated group than those in control group, suggesting the beneficial effect of PIO on endothelial function in T2DM"
• Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus - Metabolism. 2009 Jun;58(6):739-45 - "pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement"
• Pioglitazone Improves Cardiac Function and Alters Myocardial Substrate Metabolism Without Affecting Cardiac Triglyceride Accumulation and High-Energy Phosphate Metabolism in Patients With Well-Controlled Type 2 Diabetes Mellitus - Circulation. 2009 Apr 6 - "were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks ... No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P<0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (P=0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content" - I still take pioglitazone even though I don't have diabetes because I feel that higher glucose levels are a major cause of aging.  There doesn't seem to be any evidence that it has the heart rises that rosiglitazone has.  See Pioglitazone at OffshoreRx1.com.
• Thiazolidinediones: effects on the development and progression of type 2 diabetes and associated vascular complications - Diabetes Metab Res Rev. 2009 Feb 13;25(2):112-126 - "In 2008, an update of an American Diabetes Association-European Association for the Study of Diabetes consensus statement on initiation and adjustment of therapy in patients with type 2 diabetes advised clinicians against using rosiglitazone. Skeletal fractures have recently emerged as a side effect of both TZDs. Available data suggest that cardiovascular benefits observed with pioglitazone might not be a class effect of TZDs"
• Thiazolidinediones inhibit REG Ialpha gene transcription in gastrointestinal cancer cells - Biochem Biophys Res Commun. 2008 Dec 29 - "TZDs may therefore be a candidate for novel anti-cancer drugs for patients with gastrointestinal cancer expressing both REG Ialpha and PPARgamma"
• Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction - Congest Heart Fail. 2008 Nov-Dec;14(6):335 - "Pioglitazone was associated with a higher incidence of hospitalization for HF without an increase in cardiovascular mortality or worsening cardiac function (by echocardiography)"
• Pioglitazone effects on blood pressure in patients with metabolic syndrome - Nippon Rinsho. 2008 Aug;66(8):1591-5 - "Although blood pressure lowering effect of pioglitazone is small, several clinical trials and a meta-analysis indicated that it decreases both systolic and diastolic blood pressure. Pioglitazone has favorable effects on important components of metabolic syndrome including blood pressure"
• Acarbose Treatment Increases Serum Total Adiponectin Levels in Patients with Type 2 Diabetes - Endocr J. 2008 May 15 - "Treatment with acarbose and pioglitazone decreased HbA1c values by 0.49 % and 0.63 %, respectively. Pioglitazone, as expected, increased serum levels of total adiponectin by 2.1 fold and its high molecular weight isoform by 3.6 fold. We found that acarbose also caused a small but significant increase in serum concentrations of total adiponectin. However, in contrast to pioglitazone, no appreciable changes were observed in the levels of high molecular weight adiponectin"
• Peroxisome Proliferator-Activated Receptor gamma agonism modifies the effects of growth hormone on lipolysis and insulin sensitivity - Clin Endocrinol (Oxf). 2008 Mar 10 - "Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) agonists such as thiazolidinediones (TZD) improve insulin sensitivity in type 2 diabetes via effects on fat metabolism, whereas growth hormone (GH) stimulates lipolysis and induces insulin resistance ...Randomized, placebo-controlled, double-blind parallel-group study including 20 GH-deficient patients on continued GH replacement therapy. The patients were studied before and after 12 weeks ... Adiponectin levels almost doubled during pioglitazone treatment (P = 0.0001). Pioglitazone significantly decreased basal free fatty acid levels (P = 0.02) and lipid oxidation (P = 0.02). Basal glucose oxidation rate (P = 0.004) and insulin sensitivity (P = 0.03) improved in the patients who received pioglitazone treatment. The change in insulin-stimulated adiponectin level after pioglitazone treatment was positively correlated to the change in insulin-stimulated total glucose disposal (R = 0.69 ... The impact of GH on lipolysis and insulin sensitivity is modifiable by administration administration of TZD"
• The PPARgamma agonist pioglitazone is effective in the MPTP mouse model of Parkinson's disease through inhibition of monoamine oxidase B - Br J Pharmacol. 2008 Mar 10 - "The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist pioglitazone has previously been shown to attenuate dopaminergic cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease, an effect attributed to its anti-inflammatory properties. In the present investigation, we provide evidence that pioglitazone is effective in the MPTP mouse model, not via an anti-inflammatory action, but through inhibition of MAO-B, the enzyme required to biotransform MPTP to its active neurotoxic metabolite 1-methyl-4-phenylpyridinium (MPP+) ... Mice treated with MPTP showed deficits in motor performance, marked depletions in striatal dopamine levels and a concomitant reduction in TH immunoreactivity in the substantia nigra. Pretreatment with pioglitazone completely prevented these effects of MPTP. However, pretreatment with pioglitazone also significantly inhibited the MPTP-induced production of striatal MPP+ and the activity of MAO-B in the striatum"
• Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia a randomized, double-blind, placebo-controlled study - J Am Coll Cardiol. 2007 Nov 20;50(21):2051-8 - "myocardial glucose utilization (MGU) and blood flow (MBF) in nondiabetic patients with familial combined hyperlipidemia (FCHL) ... in the pioglitazone group HDL cholesterol (+28%; p = 0.003) and adiponectin (+156.2%; p = 0.0001) were increased and plasma insulin (-35%; p = 0.017) was reduced ... In patients with FCHL treated with conventional lipid-lowering therapy, the addition of pioglitazone led to significant improvements in MGU and MBF, with a favorable effect on blood lipid and metabolic parameters"
• Thiazolidinediones: A novel class of drugs for the prevention of diabetic nephropathy? - Kidney Int. 2007 Dec;72(11):1301-1303 - "Miyazaki et al. report that rosiglitazone, a thiazolidinedione insulin sensitizer and a potent peroxisome proliferator-activated receptor gamma agonist, not only effectively improves glycemic control but also halts progression of albuminuria in type 2 diabetic patients with early-stage diabetic nephropathy. These findings could offer a new prevention of diabetic nephropathy in insulin-resistant diabetic patients"
• Renoprotection provided by losartan in combination with pioglitazone is superior to renoprotection provided by losartan alone in patients with type 2 diabetic nephropathy - Kidney Blood Press Res. 2007;30(4):203-11 - "Renoprotection conferred by losartan combined with pioglitazone is superior to that conferred by losartan alone in subjects with type 2 diabetic nephropathy. The combination is generally well tolerated"
• Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials - Lancet. 2007 Sep 29;370(9593):1129-36 - "Compared with controls, patients given TZDs had increased risk for development of congestive heart failure across a wide background of cardiac risk (relative risk [RR] 1.72, 95% CI 1.21-2.42, p=0.002). By contrast, the risk of cardiovascular death was not increased with either of the two TZDs (0.93, 0.67-1.29, p=0.68) ... Congestive heart failure in patients given TZDs might not carry the risk that is usually associated with congestive heart failure which is caused by progressive systolic or diastolic dysfunction of the left ventricle"
• Pioglitazone Exerts Protective Effects Against Stroke in Stroke-Prone Spontaneously Hypertensive Rats, Independently of Blood Pressure - Stroke. 2007 Sep 20 - "Our work provides the first evidence that pioglitazone significantly protects against hypertension-induced cerebrovascular injury and stroke by improving vascular endothelial dysfunction, inhibiting brain inflammation, and reducing oxidative stress. These beneficial effects of pioglitazone were independent of blood pressure or blood sugar values. Thus, pioglitazone appears to be a potential therapeutic agent for stroke in type 2 diabetes with hypertension"
• Rationale for the use of insulin sensitizers to prevent cardiovascular events in type 2 diabetes mellitus - Am J Med. 2007 Sep;120(9 Suppl 2):S18-25 - "TZDs, acting via the peroxisome proliferator-activated receptor-gamma, affect a number of mediators involved in the development of the cardiovascular complications of diabetes, including lipid profiles, vascular changes, and inflammatory mediators. TZDs decrease plasminogen activator-1 and C-reactive protein levels. They also reduce the extent of thickening of the carotid artery and reduce hyperplasia after coronary stent implantation. Insulin-sensitizing therapy with TZDs is a promising intervention for patients with diabetes at risk for adverse cardiovascular outcomes"
• Pioglitazone and Risk of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Trials - JAMA. 2007 Sep 12;298(10):1180-1188 - "Pioglitazone is associated with a significantly lower risk of death, myocardial infarction, or stroke among a diverse population of patients with diabetes. Serious heart failure is increased by pioglitazone, although without an associated increase in mortality"
• The cardiovascular effects of the thiazolidinediones: a review of the clinical data - J Diabetes Complications. 2007 Sep-Oct;21(5):326-34 - "Beyond glycemic control, the thiazolidinediones (TZDs) provide numerous cardiovascular benefits. Clinical data support a role for the TZDs in lowering blood pressure, correcting dyslipidemia, improving vascular structure and function, decreasing inflammation, improving the adipokine profile, reducing systemic oxidative stress, and possibly in stabilizing coronary plaques that may be prone to rupture ... Reported side effects of the TZDs include fluid retention, worsening of heart failure, and weight gain"
• Effects of early use of pioglitazone in combination with metformin in patients with newly diagnosed type 2 diabetes - Curr Med Res Opin. 2007 Aug;23(8):1775-81 - "early use of combination therapy at time of diagnosis or within the first 3-6 months following diagnosis with metformin plus pioglitazone in newly diagnosed type 2 diabetes results in a slower deterioration in glycaemic control than that with metformin combined with either gliclazide or repaglinide. This may be due to the beta-cell protective properties of pioglitazone"
• Effects of pioglitazone on lipid and lipoprotein metabolism - Diabetes Obes Metab. 2007 Sep;9(5):640-7 - "In the monotherapy setting, pioglitazone has been associated with greater decreases in TGs and increases in HDL-C when compared with glibenclamide or metformin. Studies investigating the effects of pioglitazone add-on therapy to either metformin or sulphonylurea treatments have shown sustained improvements in serum levels of TGs and HDL-C and favourable effects on LDL-C particle size. In comparison with rosiglitazone, pioglitazone has different and potentially favourable effects on plasma lipids. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events study has given weight to the hypothesis that the beneficial metabolic effects of pioglitazone may be associated with reductions in cardiovascular risk in patients with type 2 diabetes" - Note:  When I switched from pioglitazone to rosiglitazone, my HDL when from 57 to 47.  I'm switching back when I run out of rosiglitazone.  I've been taking them to prevent diabetes.
• Effects of pioglitazone on lipid and lipoprotein metabolism - Diabetes Obes Metab. 2007 Sep;9(5):640-7 - "In the monotherapy setting, pioglitazone has been associated with greater decreases in TGs and increases in HDL-C when compared with glibenclamide or metformin. Studies investigating the effects of pioglitazone add-on therapy to either metformin or sulphonylurea treatments have shown sustained improvements in serum levels of TGs and HDL-C and favourable effects on LDL-C particle size. In comparison with rosiglitazone, pioglitazone has different and potentially favourable effects on plasma lipids. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events study has given weight to the hypothesis that the beneficial metabolic effects of pioglitazone may be associated with reductions in cardiovascular risk in patients with type 2 diabetes"
• Effects of thiazolidinediones on blood pressure - Curr Hypertens Rep. 2007 Aug;9(4):332-7 - "The magnitude of reduction appears to be about 4 to 5 mm Hg in systolic and 2 to 4 mm Hg in diastolic BP-sufficient to significantly reduce subsequent cardiovascular event rates"
• Pioglitazone Use and Heart Failure in Patients with Type 2 Diabetes and Preexisting Cardiovascular Disease: Data from the PROactive Study (PROactive 08) - Diabetes Care. 2007 Jul 31 - "serious HF (SHF) ... More pioglitazone (5.7%) than placebo patients (4.1%) had a SHF event during the study (P=0.007). However, mortality due to HF was similar (25/2605 [0.96%] for pioglitazone versus 22/2633 [0.84%] for placebo; P=0.639). Among patients with a SHF event, subsequent all-cause mortality was proportionately lower with pioglitazone (40/149 [26.8%]) versus 37/108 [34.3%] with placebo; P=0.1338). Proportionately fewer pioglitazone patients with SHF went on to have an event in the primary (47.7% with pioglitazone versus 57.4% with placebo; P=0.0593) or main secondary endpoint (34.9% with pioglitazone versus 47.2% with placebo; P=0.025)"
• Pioglitazone Decreases Ambulatory Blood Pressure in Type 2 Diabetics With Difficult-to-Control Hypertension - J Clin Hypertens (Greenwich). 2007 Jul;9(7):530-7 - "add-on therapy with pioglitazone 30 to 45 mg for 20 weeks. After 20 weeks of treatment, 24-hour ambulatory BP monitoring showed significant reductions (from 144+/-13 to 136+/-16 mm Hg systolic BP and from 79+/-9 to 76+/-10 mm Hg diastolic BP [P=.001]). Treatment was also associated with improvements in insulin sensitivity and glycemic and lipid profile"
• The impact of thiazolidinedione use on outcomes in ambulatory patients with diabetes mellitus and heart failure - J Am Coll Cardiol. 2007 Jul 3;50(1):32-6 - "In ambulatory patients with established HF and diabetes, the use of TZDs was not associated with an increased risk of HF hospitalization or total mortality when compared with those not receiving insulin-sensitizing medications"
• Pioglitazone and Rosiglitazone Have Different Effects on Serum Lipoprotein Particle Concentrations and Sizes in Patients with Type 2 Diabetes and Dyslipidemia - Diabetes Care. 2007 Jun 26 - "PIO-treatment increased total VLDL particle concentration less than ROSI-treatment and decreased VLDL particle size more than ROSI. PIO-treatment reduced total LDL particle concentration whereas ROSI-treatment increased it. Both treatments increased LDL particle size, with PIO-treatment having a greater effect. Whereas PIO-treatment increased total HDL particle concentration and size, ROSI-treatment decreased them; both increased HDL cholesterol levels"
• Pioglitazone has anti-inflammatory effects in patients with Type 2 diabetes - J Endocrinol Invest. 2007 Apr;30(4):292-7 - "Pioglitazone treatment results in reduced A1GP concentration suggesting an anti-inflammatory effect"
• The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study - J Am Coll Cardiol. 2007 May 1;49(17):1772-80 - "In high-risk patients with type 2 diabetes and previous MI, pioglitazone significantly reduced the occurrence of fatal and nonfatal MI and ACS"
• Treating the metabolic syndrome - Expert Rev Cardiovasc Ther. 2007 May;5(3):491-506 - "appropriate treatment of MS components often requires pharmacologic intervention with insulin-sensitizing agents, such as metformin and thiazolidinediones, while statins and fibrates, or angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the first-line lipid-modifying or antihypertensive drugs"
• Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: Relation to liver, muscle and regional body fat content - Atherosclerosis. 2007 May 4 - "Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) -32.3% (p=0.002), plasma glucose -4.4% (p=0.03), alanine-aminotransferase (ALT) -7.7% (p=0.005) and adiponectin 130.1% (p=0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p=0.02) and subcutaneous (7.1%, p=0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p=0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated (r=0.72, p<0.01; r=.0.86, p<0.01, respectively). In patients with FCHL on conventional lipid-lowering therapy, the addition of pioglitazone acts favourably on several metabolic parameters"
• Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes - J Clin Oncol. 2007 Apr 20;25(12):1476-81 - "We observed a 33% reduction in lung cancer risk among TZD users compared with nonusers after adjusting for confounder interactions ... The risk reduction for colorectal and prostate cancers did not reach statistical significance"
• Thiazolidinediones and vascular damage - Current Opinion in Endocrinology, Diabetes & Obesity. 14(2):108-115, April 2007 - "The thiazolidinedione class improves endothelial vasomotion, inhibits inflammatory and procoagulant processes and has powerful antiproliferative and antioxidant effects. Experimentally these agents retard atherosclerosis development in predisposed animals. Clinical studies demonstrate that they increase HDL cholesterol and LDL size, and may lower triglyceride levels. They modestly lower blood pressure, reduce microalbuminuria, arterial stiffness and reduce carotid wall thickening. These effects are generally independent of glucose lowering and in many instances have been shown to occur in nondiabetic subjects"
• Effects of Pioglitazone in Patients With Type 2 Diabetes With or Without Previous Stroke. Results From PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04) - Stroke. 2007 Feb 8 - "In a subgroup analysis from PROactive, pioglitazone reduced the risk of recurrent stroke significantly in high-risk patients with type 2 diabetes"
• Effect of pioglitazone on atherogenic outcomes in type 2 diabetic patients: A comparison of responders and non-responders - Diabetes Res Clin Pract. 2007 Feb 1 - "These results strongly suggest that pioglitazone is beneficial for type 2 diabetic patients with high levels of BMI, HOMA-IR, LDL-C, and RLP-C, as it helps to prevent the progression of atherosclerosis, including coronary heart diseases"
• Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with metformin - Intern Med J. 2007 Feb;37(2):79-86 - "Significant total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement was observed in pioglitazone group after 12 months, but not in the rosiglitazone group"
• Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes - Hypertens Res. 2007 Jan;30(1):23-30 - "pioglitazone was superior to metformin for the improvement of insulin resistance and adiponectin ... Early intervention with pioglitazone or metformin therapy may reduce the incidence of future cardiovascular disease in subjects with impaired glucose tolerance or early diabetes"
• Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men - Atherosclerosis. 2006 Dec 2 - "Pioglitazone and fenofibrate treatment of obese, glucose tolerant men reduces inflammation, improves markers of endothelial function and reduces arterial stiffness. These results suggest that treatment with PPAR agonists has potential to reduce the incidence of premature cardiovascular disease associated with obesity"
• Effects of rosiglitazone and pioglitazone combined with metformin on the prothrombotic state of patients with type 2 diabetes mellitus and metabolic syndrome - J Int Med Res. 2006 Sep-Oct;34(5):545-55 - "In patients with type 2 diabetes mellitus and metabolic syndrome, the combination of metformin plus thiazolidinediones improved glycaemic control and produced a slight but significant reduction in plasminogen activator inhibitor-1 levels"
• Effect of Pioglitazone Compared With Glimepiride on Carotid Intima-Media Thickness in Type 2 Diabetes: A Randomized Trial - JAMA, 12/6/06 - "Carotid artery intima-media thickness (CIMT) is a marker of coronary atherosclerosis and independently predicts cardiovascular events ... Over an 18-month treatment period in patients with type 2 DM, pioglitazone slowed progression of CIMT compared with glimepiride"
• Assessment of left ventricular diastolic function with pioglitazone in type 2 diabetic patients - J Cardiol. 2006 Nov;48(5):263-7 - "Pioglitazone administration improves and cessation worsens left ventricular diastolic function"
• A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis - N Engl J Med. 2006 Nov 30;355(22):2297-307 - "Diet plus pioglitazone, as compared with diet plus placebo, improved glycemic control and glucose tolerance (P<0.001), normalized liver aminotransferase levels as it decreased plasma aspartate aminotransferase levels (by 40% vs. 21%, P=0.04), decreased alanine aminotransferase levels (by 58% vs. 34%, P<0.001), decreased hepatic fat content (by 54% vs. 0%, P<0.001), and increased hepatic insulin sensitivity (by 48% vs. 14%"
• Metformin and pioglitazone: Effectively treating insulin resistance - Curr Med Res Opin. 2006;22 Suppl 2:S27-37 - "The different insulin-sensitizing mechanisms of metformin and the thiazolidinediones are manifest in partially distinct effects on hepatic and peripheral glucose homeostasis, and clinical studies show improved glucose control with combination therapy. Both metformin and thiazolidinediones may also have pancreatic beta-cell preserving properties. Furthermore, they have different beneficial effects on several other metabolic risk markers and risk factors for cardiovascular disease. Whereas the thiazolidinediones (particularly pioglitazone) have greater effects on multiple aspects of dyslipidemia, metformin has anorexigenic properties. They also have distinct effects on levels of mediators involved in inflammation and endothelial dysfunction, and outcome studies suggest that either pioglitazone or metformin may reduce the risk of macrovascular events"
• A fixed-dose combination of pioglitazone and metformin: A promising alternative in metabolic control - Curr Med Res Opin. 2006;22 Suppl 2:S39-48 - "Pioglitazone increases insulin sensitivity, while metformin reduces hepatic gluconeogenesis and improves peripheral glucose uptake. Both agents reduce hyperglycemia and hyperinsulinemia, and appear to protect beta-cell function ... In randomized studies, pioglitazone and metformin administered separately provided significantly better glycemic control than metformin monotherapy or metformin plus gliclazide. Pioglitazone and metformin have complimentary benefits on diabetic dyslipidemia; pioglitazone primarily improves high-density lipoprotein cholesterol and triglyceride levels (to a greater extent than rosiglitazone does), while metformin mainly improves total cholesterol. Pioglitazone and metformin also modulate other atherosclerosis biomarkers, including inflammatory mediators, coagulation thrombosis components, and carotid intima media thickness. Together, these pleiotropic effects have the potential to confer a reduced risk of cardiovascular disease in patients with type 2 diabetes. Pioglitazone and metformin are well tolerated in combination, with low rates of hypoglycemia, and the convenience of a single tablet may be expected to aid dosing compliance"
• Hepatic safety profile and glycemic control of pioglitazone in more than 20,000 patients with type 2 diabetes mellitus: Postmarketing surveillance study in Japan - Diabetes Res Clin Pract. 2006 Nov 14 - "No case of hepatic failure was reported, and neither temporal nor dose relations were found between pioglitazone and ALT abnormalities"
• Long-term Safety of Pioglitazone versus Glyburide in Patients with Recently Diagnosed Type 2 Diabetes Mellitus - Pharmacotherapy. 2006 Oct;26(10):1388-95 - "With long-term treatment, both glyburide and pioglitazone resulted in comparable glycemic control; however, pioglitazone was associated with less hypoglycemia and fewer withdrawals due to lack of efficacy or adverse events"
• Pioglitazone: an antidiabetic drug with cardiovascular therapeutic effects - Expert Rev Cardiovasc Ther. 2006 Jul;4(4):445-59 - "the use of pioglitazone in addition to an existing optimized macrovascular risk management resulted in a significant reduction of macrovascular endpoints within a short observation period that was comparable to the effect of statins and angiotensin converting enzyme inhibitors in other trials"
• Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome - J Clin Pharm Ther. 2006 Aug;31(4):375-83 - "Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study"
• Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes - Diabetes Care. 2006 Mar;29(3):510-4 - "pioglitazone increases total body water, thereby accounting for the majority of weight gain, tended to decrease visceral and abdominal fat content and blood pressure, and reduces systemic vascular resistance"
• TNF-{alpha} induces endothelial dysfunction in diabetic adults, an effect reversible by the PPAR-{gamma} agonist pioglitazone - Eur Heart J. 2006 Jun 8 - "Pioglitazone treatment can convey direct protection against cytokine (TNF-alpha)-induced endothelial dysfunction in humans with an increased cardiovascular risk due to type 2 diabetes"
• Effect of pioglitazone on insulin sensitivity, vascular function and cardiovascular inflammatory markers in insulin-resistant non-diabetic Asian Indians - Diabet Med. 2006 May;23(5):537-43 - "These agents may have a role in decreasing the risk of diabetes and cardiovascular disease in this high-risk population"
• Effects of pioglitazone on endothelial function, insulin sensitivity, and glucose control in subjects with coronary artery disease and new-onset type 2 diabetes - Diabetes Care. 2006 May;29(5):1039-45 - "After 12 weeks, endothelial dysfunction was significantly better in the pioglitazone group ... Pioglitazone improves endothelial dysfunction independently from the observed benefits on insulin sensitivity and beta-cell function in patients with newly diagnosed type 2 diabetes and CAD"
• Insulin resistance - a common link between type 2 diabetes and cardiovascular disease - Diabetes Obes Metab. 2006 May;8(3):237-249 - "In addition to lifestyle changes, PPARgamma agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPARalpha (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events. The development of agents with both PPARalpha and PPARgamma activity promises added benefits with amelioration of insulin resistance, delayed progression to and of type 2 diabetes and a reduction of CVD"
• Do thiazolidinediones cause heart failure? A critical review - Cleve Clin J Med. 2006 Apr;73(4):390-7 - "TZDs, ie, rosiglitazone and pioglitazone ... Although fluid retention is a worrisome side effect of TZDs, current evidence does not link fluid retention caused by TZDs with worsening heart function"
• Thiazolidinedione (TZD) Use and Bone Loss in Older Diabetic Adults - J Clin Endocrinol Metab. 2006 Apr 11 - "each year of TZD use was associated with greater bone loss at the whole body (additional loss of -0.61% per year; 95% CI: -1.02, -0.21% per year), lumbar spine (-1.23% per year; 95% CI: -2.06, -0.40% per year), and trochanter (-0.65% per year; 95% CI: -1.18, -0.12% per year) in women, but not men, with diabetes"
• Thiazolidinedione effects on blood pressure in diabetic patients with metabolic syndrome treated with glimepiride - Hypertens Res. 2005 Nov;28(11):917-24 - "the association of a thiazolinedione to the glimepiride treatment of type 2 diabetic subjects with metabolic syndrome is associated to a significant improvement in the long-term blood pressure control, related to a reduction in insulin-resistance"
• Proactive study: secondary cardiovascular prevention with pioglitazione in type 2 diabetic patients - Rev Med Liege. 2005 Nov;60(11):896-901
• Cardiovascular effects of the thiazolidinediones - Diabetes Metab Res Rev. 2005 Sep 26 - "thiazolidinediones have beneficial effects on the cardiovascular system independent of their antidiabetic effect. Studies in animals have clearly shown that thiazolidinediones decrease blood pressure, left ventricular hypertrophy, development of atherosclerotic lesions, and protect myocardium from ischemia/reperfusion injury"