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Home > Health Conditions > Diabetes > Actos (pioglitazone HCL)

Actos (pioglitazone HCl) - Eli Lilly & Co.

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Abstracts:

  • 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 OffshoreRX.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 OffshoreRX.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 OffshoreRX.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 OffshoreRX.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 OffshoreRX.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"
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