nach oben

Current Diabetes Reports

Erschienen in:

01.06.2013 | Pharmacologic Treatment of Type 2 Diabetes and Obesity (A Vella, Section Editor)

The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus

verfasst von: Hanford Yau, Kathya Rivera, Romina Lomonaco, Kenneth Cusi

Erschienen in: Current Diabetes Reports | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Since their approval, thiazolidinediones (TZDs) have been used extensively as insulin-sensitizers for the management of type 2 diabetes mellitus (T2DM). Activation of peroxisomal proliferator-activated receptor gamma (PPARγ) nuclear receptors by TZDs leads to a vast spectrum of metabolic and antiinflammatory effects. In the past decade, clinicians and scientists across the fields of metabolism, diabetes, liver disease (NAFLD), atherosclerosis, inflammation, infertility, and even cancer have had high hopes about the potential for TZDs to treat many of these diseases. However, an increasing awareness about undesirable “off-target” effects of TZDs have made us rethink their role and be more cautious about the long-term benefits and risks related to their use. This review examines the most relevant work on the benefits and risks associated with TZD treatment, with a focus on the only PPARγ agonist currently available (pioglitazone), aiming to offer the reader a balanced overview about the current and future role of TZDs in the management of insulin-resistant states and T2DM.

Cusi K, DeFronzo R. Metformin: a review of its metabolic effects. Diabetes Rev. 1998;6:89–131.

From the Food and Drug Adminsitration. JAMA. 2000;283:2228.CrossRef

FDA significantly restricts access to the diabetes drug Avandia. In: U.S. Food and Drug Administration; 2010.

Miyazaki Y, Mahankali A, Matsuda M, et al. Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone. Diabetes Care. 2001;24:710–9.PubMedCrossRef

Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. New Engl J Med. 2006;355:2297–307.PubMedCrossRef

Tiikkainen M, Hakkinen A-M, Korsheninnikova E, et al. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes. 2004;53:2169–76.PubMedCrossRef

Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPARγ. Annu Rev Biochem. 2008;77:289–312.PubMedCrossRef

Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006;296:2572–81.PubMedCrossRef

Nissen SE, Nicholls SJ, Wolski K, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008;299:1561–73.PubMedCrossRef

10.

Pavo I, Jermendy G, Varkonyi TT, et al. Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes. J Clin Endocrinol Metab. 2003;88:1637–45.PubMedCrossRef

11.

Aljabri K, Kozak SE, Thompson DM. Addition of pioglitazone or bedtime insulin to maximal doses of sulfonylurea and metformin in type 2 diabetes patients with poor glucose control: a prospective, randomized trial. Am J Med. 2004;116:230–5.PubMedCrossRef

12.

Bell DS, Ovalle F. Long-term glycaemic efficacy and weight changes associated with thiazolidinediones when added at an advanced stage of type 2 diabetes. Diabetes Obes Metab. 2006;8:110–5.PubMedCrossRef

13.

Charbonnel B, DeFronzo R, Davidson J, et al. Pioglitazone use in combination with insulin in the prospective pioglitazone clinical trial in macrovascular events study (PROactive19). J Clin Endocrinol Metab. 2010;95:2163–71.PubMedCrossRef

14.

Scheen AJ. Combined thiazolidinedione-insulin therapy: should we be concerned about safety? Drug Saf. 2004;27:841–56.PubMedCrossRef

15.

Hohberg C, Pfutzner A, Forst T, et al. Successful switch from insulin therapy to treatment with pioglitazone in type 2 diabetes patients with residual beta-cell function: results from the PioSwitch study. Diabetes Obes Metab. 2009;11:464–71.PubMedCrossRef

16.

Okamoto T, Okamoto L, Lisanti MP, Akishita M. Switch to oral hypoglycemic agent therapy from insulin injection in patients with type 2 diabetes. Geriatr Gerontol Int. 2008;8:218–26.PubMedCrossRef

17.

Buchanan TA. (How) Can we prevent type 2 diabetes? Diabetes. 2007;56:1502–7.PubMedCrossRef

18.

Xiang AH, Peters RK, Kjos SL, et al. Effect of pioglitazone on pancreatic b-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes. 2006;55:517–22.PubMedCrossRef

19.

•• DeFronzo RA, Tripathy D, Schwenke DC, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. New Engl J Med. 2011;364:1104–15. Very important RCT on the role of pioglitazone to prevent the development of T2DM in subjects with prediabetes.PubMedCrossRef

20.

Chiquette E, Ramirez G, Defronzo R. A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors. Arch Intern Med. 2004;164:2097–104.PubMedCrossRef

21.

Nagashima K, Lopez C, Donovan D, et al. Effects of the PPARg agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus. J Clin Invest. 2005;115:1323–32.PubMed

22.

Betteridge DJ. Effects of pioglitazone on lipid and lipoprotein metabolism. Diabetes Obes Metab. 2007;9:640–7.PubMedCrossRef

23.

Al Majali K, Cooper MB, Staels B, et al. The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients. Diabetologia. 2006;49:527–37.PubMedCrossRef

24.

Deeg MA, Buse JB, Goldberg RB, et al. Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2007;30:2458–64.PubMedCrossRef

25.

Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. New Engl J Med. 2006;355:2427–43.PubMedCrossRef

26.

The DREAM. (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Role of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096–105.CrossRef

27.

Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–89.PubMedCrossRef

28.

Horio T, Suzuki M, Suzuki K, et al. Pioglitazone improves left ventricular diastolic function in patients with essential hypertension. Am J Hyperts. 2005;18:949–57.CrossRef

29.

Ogawa S, Takeuchi K, Ito S. Plasma BNP levels in the treatment of type 2 diabetes with pioglitazone. J Clin Endocrinol Metab. 2003;88:3993–6.PubMedCrossRef

30.

Sambanis C, Tziomalos K, Kountana E, et al. Effect of pioglitazone on heart function and N-terminal pro-brain natriuretic peptide levels of patients with type 2 diabetes. Acta Diabetol. 2008;45:23–30.PubMedCrossRef

31.

Guan Y, Zhang Y, Davis L, Breyer MD. Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans. Am J Phys. 1997;273:F1013–1022.

32.

Zanchi A, Chiolero A, Maillard M, et al. Effects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men. J Clin Endocrinol Metab. 2004;89:1140–5.PubMedCrossRef

33.

Zanchi A, Maillard M, Jornayvaz FR, et al. Effects of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals. Diabetologia. 2010;53:1568–75.PubMedCrossRef

34.

Guan Y, Hao C, Cha DR, et al. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med. 2005;11:861–6.PubMedCrossRef

35.

Balas B, Belfort R, Harrison S, et al. Pioglitazone treatment increases whole body fat but not total body water in patients with non-alcoholic steatohepatitis. J Hepatol. 2007;47:565–70.PubMedCrossRef

36.

Berria R, Gastaldelli A, Lucidi S, et al. Reduction in hematocrit level after pioglitazone treatment is correlated with decreased plasma free testosterone level, not hemodilution, in women with polycystic ovary syndrome. Clin Pharmacol Ther. 2006;80:105–12.PubMedCrossRef

37.

Berria R, Glass L, Mahankali A, et al. Reduction in hematocrit and hemoglobin following pioglitazone treatment is not hemodilutional in Type II diabetes mellitus. Clin Pharmacol Ther. 2007;82:275–81.PubMedCrossRef

38.

Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298:1180–8.PubMedCrossRef

39.

Hernandez AV, Usmani A, Rajamanickam A, Moheet A. Thiazolidinediones and risk of heart failure in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis and meta-regression analysis of placebo-controlled randomized clinical trials. Am J Cardiovasc Drugs. 2011;11:115–28.PubMedCrossRef

40.

Dahabreh IJ, Economopoulos K. Meta-analysis of rare events: an update and sensitivity analysis of cardiovascular events in randomized trials of rosiglitazone. Clin Trials. 2008;5:116–20.PubMedCrossRef

41.

Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 2007;298:1189–95.PubMedCrossRef

42.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. New Engl J Med. 2007;356:2457–71.PubMedCrossRef

43.

Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care. 2004;27:256–63.PubMedCrossRef

44.

Dream Trial Investigators, Dagenais GR, Gerstein HC, et al. Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. Diabetes Care. 2008;31:1007–14.PubMedCrossRef

45.

Lago RM, Singh PP, Nesto RW. 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;370:1129–36.PubMedCrossRef

46.

Masoudi FA, Inzucchi SE, Wang Y, et al. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation. 2005;111:583–90.PubMedCrossRef

47.

Rosmarakis ES, Falagas ME. Effect of thiazolidinedione therapy on restenosis after coronary stent implantation: a meta-analysis of randomized controlled trials. Am Heart J. 2007;154:144–50.PubMedCrossRef

48.

Riche DM, Valderrama R, Henyan NN. Thiazolidinediones and risk of repeat target vessel revascularization following percutaneous coronary intervention: a meta-analysis. Diabetes Care. 2007;30:384–8.PubMedCrossRef

49.

• Dormandy J, Bhattacharya M. van Troostenburg de Bruyn AR, et al.: Safety and tolerability of pioglitazone in high-risk patients with type 2 diabetes: an overview of data from PROactive. Drug Saf. 2009;32:187–202. A comprehensive in-depth analysis about the efficacy and safety of a TZD in the largest RCT ever perfromed in patients with T2DM and CVD.PubMedCrossRef

50.

Hirano M, Nakamura T, Kitta Y, et al. Rapid improvement of carotid plaque echogenicity within 1 month of pioglitazone treatment in patients with acute coronary syndrome. Atherosclerosis. 2009;203:483–8.PubMedCrossRef

51.

Saremi A, Schwenke DC, Buchanan TA, et al. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2013;33:393–9.PubMedCrossRef

52.

Erdmann E, Dormandy JA, Charbonnel B, et al. 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. JACC. 2007;49:1772–80.PubMedCrossRef

53.

Grey A. Skeletal consequences of thiazolidinedione therapy. Osteoporos Int. 2008;19:129–37.PubMedCrossRef

54.

Kahn SE, Zinman B, Lachin JM, et al. Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care. 2008;31:845–51.PubMedCrossRef

55.

Spanheimer R. Observation of an increased incidence of fractures in female patients who received long-term treatment with ACTOS (pioglitazone HOI) tablets for type 2 diabetes mellitus. In: 2007.

56.

Colhoun HM, Livingstone SJ, Looker HC, et al. Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs. Diabetologia. 2012;55:2929–37.PubMedCrossRef

57.

Habib ZA, Havstad SL, Wells K, et al. Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95:592–600.PubMedCrossRef

58.

Bilik D, McEwen LN, Brown MB, et al. Thiazolidinediones and fractures: evidence from translating research into action for diabetes. J Clin Endocrinol Metab. 2010;95:4560–5.PubMedCrossRef

59.

Bazelier MT, Gallagher AM, van Staa TP, et al. Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Pharmacoepidemiol Drug Saf. 2012;21:507–14.PubMedCrossRef

60.

Hsiao FY, Mullins CD. The association between thiazolidinediones and hospitalisation for fracture in type 2 diabetic patients: a Taiwanese population-based nested case-control study. Diabetologia. 2010;53:489–96.PubMedCrossRef

61.

Bazelier MT, Vestergaard P, Gallagher AM, et al. Risk of fracture with thiazolidinediones: disease or drugs? Calcif Tissue Int. 2012;90:450–7.PubMedCrossRef

62.

Aubert R, Herrera V, Chen W, et al. Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes. Diabetes Obes Metab. 2010;12:716–21.PubMedCrossRef

63.

Mieczkowska A, Basle MF, Chappard D, Mabilleau G. Thiazolidinediones induce osteocyte apoptosis by a G protein-coupled receptor 40-dependent mechanism. J Biol Chem. 2012;287:23517–26.PubMedCrossRef

64.

Seth A, Sy V, Pareek A, et al. Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers independently of the TZD effects on aromatase. Horm Metab Res. 2013;45:1–8.PubMed

65.

Lazarenko O, Rzonca S, Hogue W, et al. Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology. 2007;148:2669–80.PubMedCrossRef

66.

Ali A, Weinstein R, Stewart S, et al. Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. Endocrinology. 2005;146:1226–35.PubMedCrossRef

67.

Liu L, Aronson J, Huang S, et al. Rosiglitazone inhibits bone regeneration and causes significant accumulation of fat at sites of new bone formation. Calcif Tissue Int. 2012;91:139–48.PubMedCrossRef

68.

• Beck Jr GR, Khazai NB, Bouloux GF, et al. The effects of thiazolidinediones on human bone marrow stromal cell differentiation in vitro and in thiazolidinedione-treated patients with type 2 diabetes. Trans Res. 2013;161:145–55. This study provides a basic and clinical translational explanation on how TZDs may cause bone loss during treament of patients with T2DM.CrossRef

69.

Zinman B, Haffner SM, Herman WH, et al. Effect of rosiglitazone, metformin, and glyburide on bone biomarkers in patients with type 2 diabetes. J Clin Endocrinol Metab. 2010;95:134–42.PubMedCrossRef

70.

Oei L, Zillikens MC, Dehghan A et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: The Rotterdam Study. Diabetes Care. 2013 (epub ahead of print).

71.

Plissonnier ML, Fauconnet S, Bittard H, Lascombe I. The antidiabetic drug ciglitazone induces high grade bladder cancer cells apoptosis through the up-regulation of TRAIL. PloS One. 2011;e28354.

72.

Li MY, Kong AW, Yuan H, et al. Pioglitazone prevents smoking carcinogen-induced lung tumor development in mice. Curr Cancer Drug Targets. 2012;12:597–606.PubMedCrossRef

73.

Lee MW, Kim DS, Kim HR, et al. Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, independently of PPARgamma in human glioma cells. Biochem Biophys Res Commun. 2012;417:552–7.PubMedCrossRef

74.

Yang X, So WY, Ma RC, et al. Use of thiazolidinedione and cancer risk in Type 2 diabetes: the Hong Kong diabetes registry. Diabetes Res Clin Pract. 2012;97:e13–17.PubMedCrossRef

75.

Colmers IN, Bowker SL, Johnson JA. Thiazolidinedione use and cancer incidence in type 2 diabetes: a systematic review and meta-analysis. Diabetes Metab. 2012;38:475–84.PubMedCrossRef

76.

Pishvaian MJ, Marshall JL, Wagner AJ, et al. A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies. Cancer. 2012;118:5403–13.PubMedCrossRef

77.

Lai SW, Chen PC, Liao KF, et al. Risk of hepatocellular carcinoma in diabetic patients and risk reduction associated with anti-diabetic therapy: a population-based cohort study. Am J Gastroenterol. 2012;107:46–52.PubMedCrossRef

78.

Walter B, Schrettenbrunner I, Vogelhuber M, et al. Pioglitazone, etoricoxib, interferon-alpha, and metronomic capecitabine for metastatic renal cell carcinoma: final results of a prospective phase II trial. Med Oncol. 2012;29:799–805.PubMedCrossRef

79.

Chang CH, Lin JW, Wu LC, et al. Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus. Hepatology. 2012;55:1462–72.PubMedCrossRef

80.

He XX, Tu SM, Lee MH, Yeung SC. Thiazolidinediones and metformin associated with improved survival of diabetic prostate cancer patients. Ann Oncol. 2011;22:2640–5.PubMedCrossRef

81.

He X, Esteva FJ, Ensor J, et al. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann Oncol. 2012;23:1771–80.PubMedCrossRef

82.

Neumann A, Weill A, Ricordeau P, et al. Pioglitazone and risk of bladder cancer among diabetic patients in France: a population-based cohort study. Diabetologia. 2012;55:1953–62.PubMedCrossRef

83.

Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011;34:916–22.PubMedCrossRef

84.

Mamtani R, Haynes K, Bilker WB, et al. Association between longer therapy with thiazolidinediones and risk of bladder cancer: a cohort study. J Nat Cancer Inst. 2012;104:1411–21.PubMedCrossRef

85.

Tseng CH. Diabetes and risk of bladder cancer: a study using the National Health Insurance database in Taiwan. Diabetologia. 2011;54:2009–15.PubMedCrossRef

86.

Tseng CH. Pioglitazone and bladder cancer: a population-based study of Taiwanese. Diabetes Care. 2012;35:278–80.PubMedCrossRef

87.

Fujimoto K, Hamamoto Y, Honjo S et al. Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract. 2012 (epub ahead of print).

88.

Song SO, Kim KJ, Lee BW, Kang ES, Cha BS, Lee HC. The risk of bladder cancer in korean diabetic subjects treated with pioglitazone. Diabetes Metab. 2012;36:371–8.CrossRef

89.

Tseng CH. Pioglitazone and bladder cancer in human studies: is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities? J Form Med Assoc. 2012;111:123–31.CrossRef

90.

Solomon CG, Hu FB, Dunaif A, et al. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab. 2002;87:2013–7.PubMedCrossRef

91.

Nestler J. Metformin for the treatment of the polycystic ovary syndrome. New Engl J Med. 2008;358:47–54.PubMedCrossRef

92.

Legro RS, Barnhart HX, Schlaff WD, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. New Engl J Med. 2007;356:551–66.PubMedCrossRef

93.

Li XJ, Yu YX, Liu CQ, et al. Metformin vs thiazolidinediones for treatment of clinical, hormonal and metabolic characteristics of polycystic ovary syndrome: a meta-analysis. Clin Endocrinol. 2011;74:332–9.CrossRef

94.

Du Q, Wang YJ, Yang S, et al. A systematic review and meta-analysis of randomized controlled trials comparing pioglitazone versus metformin in the treatment of polycystic ovary syndrome. Curr Med Res Opin. 2012;28:723–30.PubMedCrossRef

95.

Aroda VR, Ciaraldi TP, Burke P, et al. Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2009;94:469–76.PubMedCrossRef

96.

Naka KK, Kalantaridou SN, Kravariti M, et al. Effect of the insulin sensitizers metformin and pioglitazone on endothelial function in young women with polycystic ovary syndrome: a prospective randomized study. Fertil Steril. 2011;95:203–9.PubMedCrossRef

97.

Ibanez L, Lopez-Bermejo A, Diaz M, et al. Low-dose pioglitazone, flutamide, metformin plus an estro-progestagen for non-obese young women with polycystic ovary syndrome: increasing efficacy and persistent safety over 30 months. Gynecol Endocrinol. 2010;26:869–73.PubMedCrossRef

98.

Vinaixa M, Rodriguez MA, Samino S et al. Metabolomics reveals reduction of metabolic oxidation in women with polycystic ovary syndrome after pioglitazone-flutamide-metformin polytherapy. PloS one. 2011;e29052.

99.

Practice Committee of the American Society for Reproductive Medicine. Use of insulin-sensitizing agents in the treatment of polycystic ovary syndrome. Fertil Steril. 2008;90:S69–73.

100.

Bulletins--Gynecology ACoP. ACOG Practice Bulletin No. 108. Polycystic ovary syndrome. Obstet Gynecol. 2009;114:936–49.CrossRef

101.

Roy KK, Baruah J, Sharma A, et al. A prospective randomized trial comparing the clinical and endocrinological outcome with rosiglitazone versus laparoscopic ovarian drilling in patients with polycystic ovarian disease resistant to ovulation induction with clomiphene citrate. Arch Gynecol Obstet. 2010;281:939–44.PubMedCrossRef

102.

•• Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142:711–25. Comprehensive review on the role of obesity and dysfunctional adipose tissue in the development of nonalcoholic steatohepatitis (NASH), associated comorbidities such as insulin resistance, T2DM, and CVD and an overview of current treatments.PubMedCrossRef

103.

•• Torres DM, Williams CD, Harrison SA. Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012;10:837–58. Excellent review on the pathogenesis, clinical profile and diagnostic and treatment approaches for nonalcoholic fatty liver disease (NAFLD).PubMedCrossRef

104.

• Lomonaco R, Ortiz-Lopez C, Orsak B, et al. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology. 2012;55:1389–97. In this study, the authors highlight the relative importance of dysfunctional fat, over BMI per se, in the development of metabolic and histological abnormalities in patients with NAFLD.PubMedCrossRef

105.

• Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. New Engl J Med. 2010;362:1675–85. The largest RCT in patients with NASH that highlights the clinical efficacy of vitamin E or pioglitazone in patients without diabetes with this condition.PubMedCrossRef

106.

• Ratziu V, Caldwell S, Neuschwander-Tetri BA. Therapeutic trials in nonalcoholic steatohepatitis: insulin sensitizers and related methodological issues. Hepatology. 2010;52:2206–15. A comprehensive review of clinical trials in patients with NASH.PubMedCrossRef

107.

Aithal GP, Thomas JA, Kaye PV, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology. 2008;135:1176–84.PubMedCrossRef

108.

Ratziu V, Giral P, Jacqueminet S, et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology. 2008;135:100–10.PubMedCrossRef

109.

Ratziu V, Charlotte F, Bernhardt C, et al. Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial. Hepatology. 2010;51:445–53.PubMedCrossRef

110.

Henriksen K, Byrjalsen I, Qvist P, et al. Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy. Diabetes Metab Res Rev. 2011;27:392–401.PubMedCrossRef

111.

Herz M, Gaspari F, Perico N, et al. Effects of high dose aleglitazar on renal function in patients with type 2 diabetes. Int J Cardiol. 2011;151:136–42.PubMedCrossRef

Titel: The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus
verfasst von: Hanford Yau
Kathya Rivera
Romina Lomonaco
Kenneth Cusi
Publikationsdatum: 01.06.2013
Verlag: Current Science Inc.
Erschienen in: Current Diabetes Reports / Ausgabe 3/2013
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-013-0378-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

16.04.2024 | Chronische Herzinsuffizienz | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Sind Betablocker auch für ältere herzschwache Personen nützlich?

Kein Abstrich bei chronischen Wunden ohne Entzündungszeichen!

Manche Gestagene können das Risiko für Meningeome erhöhen

Stillende Frauen haben geringeres kardiovaskuläres Risiko

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2013

Is the Risk and Nature of CVD the Same in Type 1 and Type 2 Diabetes?

Vascular Calcification in Diabetes: Mechanisms and Implications

Nuclear Factor (Erythroid-Derived 2)-Like-2 Factor (Nrf2), a Key Regulator of the Antioxidant Response to Protect Against Atherosclerosis and Nonalcoholic Steatohepatitis

Risk vs Benefit in Diabetes Pharmacotherapy: a Rational Approach to Choosing Pharmacotherapy in Type 2 Diabetes

Insulin Use Early in the Course of Type 2 Diabetes Mellitus: The ORIGIN Trial

Diabetes Mellitus and Periodontal Diseases

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Sind Betablocker auch für ältere herzschwache Personen nützlich?

Kein Abstrich bei chronischen Wunden ohne Entzündungszeichen!

Manche Gestagene können das Risiko für Meningeome erhöhen

Stillende Frauen haben geringeres kardiovaskuläres Risiko

Update Innere Medizin