Pleiotropic Effects of Thiazolidinediones: Implications for the Treatment of Patients With Type 2 Diabetes Mellitus

References

• . Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004; 351(11):1106–1118
   PubMed Web of Science ®Google Scholar
• . Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457–2471
   PubMed Web of Science ®Google Scholar
• . Dormandy JA, Charbonnel B, Eckland DJA, ; PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macro Vascular Events): a randomised controlled trial. Lancet. 2005;366(9493): 1279–1289
   PubMed Web of Science ®Google Scholar
• . Bajaj M, Suraamornkul S, Hardies LJ, Glass L, Musi N, DeFronzo RA. Effects of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus. Diabetologia. 2007;50(8):1723–1731
   PubMedGoogle Scholar
• . Avogaro A, Piliego T, Catapano A, Miola M, Tiengo A. The effect of gemfibrozil on lipid profile and glucose metabolism in hypertriglyceridaemic well-controlled non-insulin-dependent diabetic patients. For the Gemfibrozil Study Group. Acta Diabetol. 1999;36(1–2):27–33
   PubMedGoogle Scholar
• . DeFronzo RA. Banting Lecture: from the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773–795
   PubMed Web of Science ®Google Scholar
• . DeFronzo RA. Lilly Lecture, 1987. The triumvirate: beta cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988;37(6):667–687
   PubMed Web of Science ®Google Scholar
• . Eriksson J, Franssila-Kallunki A, Ekstrand A, . Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1989;321(6):337–343
   PubMed Web of Science ®Google Scholar
• . DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev. 1997;5(3):177–269
   Google Scholar
• . DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88(4):787–835
   PubMed Web of Science ®Google Scholar
• . Groop L, Lyssenko V. Genes and type 2 diabetes mellitus. Curr Diab Rep. 2008;8(3):192–197
   PubMedGoogle Scholar
• . Lyssenko V, Almgren P, Anevski D, ; Botnia Study Group. Genetic prediction of future type 2 diabetes. PLoS Med. 2005;2(12):e345
   Web of Science ®Google Scholar
• . Weyer C, Tataranni PA, Bogardus C, Pratley RE. Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. Diabetes Care. 2001;24(1):89–94
   PubMed Web of Science ®Google Scholar
• . DeFronzo RA, Ferrannini E, Simonson DC. Fasting hyperglycemia in non-insulin dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake. Metabolism. 1989;38(4):387–395
   PubMed Web of Science ®Google Scholar
• . Groop LC, Bonadonna RC, Del Prato S, . Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J Clin Invest. 1989;84(1):205–213
   PubMed Web of Science ®Google Scholar
• . Ferrannini E, Simonson DC, Katz LD, . The disposal of an oral glucose load in patients with non-insulin dependent diabetes. Metabolism. 1988;37(1):79–85
   PubMed Web of Science ®Google Scholar
• . Pendergrass M, Bertoldo A, Bonadonna R, . Muscle glucose transport and phosphorylation in type 2 diabetic, obese non-diabetic, and genetically predisposed individuals. Am J Physiol Endocrinol Metab. 2007;292(1):E92–E100
   Google Scholar
• . DeFronzo RA, Gunnarsson R, Bjorkman O, Olsson M, Wahren J. Effects of insulin on peripheral and splanchnic glucose metabolism in non-insulin-dependent (type II) diabetes mellitus. J Clin Invest. 1985;76(1):149–155
   PubMed Web of Science ®Google Scholar
• . DeFronzo RA, Diebert D, Hendler R, Felig P, Soman V. Insulin sensitivity and insulin binding in maturity onset diabetes. J Clin Invest. 1979;63(5):939–946
   PubMedGoogle Scholar
• . James WP. The fundamental drivers of the obesity epidemic. Obes Rev. 2008;9( suppl 1):6–13
   PubMedGoogle Scholar
• . DeFronzo RA, Soman V, Sherwin RS, Hendler R, Felig P. Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. J Clin Invest. 1978;62:204–213
   PubMedGoogle Scholar
• . Koivisto VA, DeFronzo RA. Physical training and insulin sensitivity. Diabetes Metab Rev. 1986;1(4):445–481
   PubMedGoogle Scholar
• . Diamond MP, Thornton K, Connolly-Diamond M, Sherwin RS, DeFronzo RA. Reciprocal variation in insulin-stimulated glucose uptake and pancreatic insulin secretion in women with normal glucose tolerance. J Soc Gynecol Investig. 1995;2(5):708–715
   PubMedGoogle Scholar
• . Zimmet P, Whitehouse S, Alford F, Chisholm D. The relationship of insulin response to a glucose stimulus over a wide range of glucose tolerance. Diabetologia. 1978;15(1):23–27
   PubMedGoogle Scholar
• . Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Mott DM, Bennett PH. Sequential changes in serum insulin concentration during development of non-insulin-dependent diabetes. Lancet. 1989;1(8651):1356–1359
   PubMedGoogle Scholar
• . Lillioja S, Mott DM, Howard BV, . Impaired glucose tolerance as a disorder of insulin action: longitudinal and cross-sectional studies in Pima Indians. N Engl J Med. 1988;318(19):1217–1225
   PubMed Web of Science ®Google Scholar
• . Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science. 2001;294(5548):1866–1870
   PubMed Web of Science ®Google Scholar
• . Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med. 2002;53:409–435
   PubMed Web of Science ®Google Scholar
• . Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res. 2000;49(10):497–505
   PubMed Web of Science ®Google Scholar
• . Dubois M, Pattou F, Kerr-Conte J, . Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in normal human pancreatic islet cells. Diabetologia. 2000;43(9):1165–1169
   PubMed Web of Science ®Google Scholar
• . Picard F, Auwerx J. PPAR(gamma) and glucose homeostasis. Annu Rev Nutr. 2002;22:167–197
   PubMed Web of Science ®Google Scholar
• . Guerre-Millo M, Gervois P, . Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000;275(22):16638–16642
   PubMed Web of Science ®Google Scholar
• . DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia. 2010;53(7):1270–1287
   PubMed Web of Science ®Google Scholar
• . Gastaldelli A, Miyazaki Y, Pettiti M, . The effect of rosiglitazone on the liver: decreased gluconeogenesis inpatients with type 2 diabetes. J Clin Endocrinol Metab. 2006;91(3):806–812
   PubMedGoogle Scholar
• . Gastaldelli A, Miyazaki Y, Mahankali A, . The effect of pioglitazone on the liver: role of adiponectin. Diabetes Care. 2006;29(10):2275–2281
   PubMedGoogle Scholar
• . Mayerson AB, Hundal RS, Dufour S, . The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes. 2002;51(3):797–802
   PubMedGoogle Scholar
• . Miyazaki Y, Mahankali A, Matsuda M, . Improved glycemic control and enhanced insulin sensitivity in liver and muscle in type 2 diabetic subjects treated with pioglitazone. Diabetes Care. 2001;24(4):710–719
   PubMed Web of Science ®Google Scholar
• . Miyazaki Y, DeFronzo RA. Rosiglitazone and pioglitazone similarly improve insulin sensitivity and secretion, glucose tolerance and adi-pocytokines in type 2 diabetic patients. Diabetes Obes Metab. 2008;10(12):1204–1211
   PubMed Web of Science ®Google Scholar
• . Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. Thiazolidinediones improve β-cell function in type 2 diabetic patients. Am J Physiol Endocrinol Metab. 2007;292(3):E871–E883
   Google Scholar
• . Mazzone T, Meyer PM, Feinstein SB, . Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA. 2006;296(21):2572–2581
   PubMed Web of Science ®Google Scholar
• . Nissen SE, Nicholls SJ, Wolski K, ; PERISCOPE Investigators. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008;299(13):1561–1573
   PubMed Web of Science ®Google Scholar
• . Kahn SE, Haffner SM, Heise MA, ; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427–2443
   PubMed Web of Science ®Google Scholar
• . Charbonnel B, Schernthaner G, Brunetti P, . Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes. Diabetologia. 2005;48(6):1093–1104
   PubMed Web of Science ®Google Scholar
• . Hanefeld M, Pfutzner A, Forst T, Lubben G. Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus: a 42-month, open-label, observational, primary care study. Cur Med Res Opin. 2006;22(6):1211–1215
   PubMed Web of Science ®Google Scholar
• . Tan MH, Baksi A, Krahulec B, ; GLAI Study Group. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care. 2005;28(3):544–550
   PubMed Web of Science ®Google Scholar
• . Rosenstock J, Goldstein BJ, Vinik AI, ; RESULT Study Group. Effect of early addition of rosiglitazone to sulphonylurea therapy in older type 2 diabetes patients (60 years): the Rosiglitazone Early vs. SULphonylurea Titration (RESULT) study. Diabetes Obes Metab. 2006;8(1):49–57
   PubMed Web of Science ®Google Scholar
• . Home PD, Jones NP, Pocock SJ, ; RECORD Study Group. Rosiglitazone RECORD study: glucose control outcomes at 18 months. Diabet Med. 2007;24(6):626–634
   PubMedGoogle Scholar
• . Viberti G, Kahn SE, Greene DA, . A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Diabetes Care. 2002;25(10):1737–1743
   PubMedGoogle Scholar
• . Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. Diabetes Care. 2000;23(11):1605–1611
   PubMed Web of Science ®Google Scholar
• . Lebovitz HE, Dole JF, Patwardhan R, Rappaport EB, Freed MI. Rosiglitazone monotherapy is effective in patients with type 2 diabetes. J Clin Endocrinol Metab. 2001;86(1):280–288
   PubMed Web of Science ®Google Scholar
• . Schernthaner G, Matthews DR, Charbonnel B, Hanefeld M, Brunetti P; Quartet Study Group. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. J Clin Endocrinol Metab. 2004;89(12):6068–6076
   PubMed Web of Science ®Google Scholar
• . Charbonnel BH, Matthews DR, Schernthaner G, Hanefeld M, Brunetti P; Quartet Study Group. A long-term comparison of pioglitazone in patients with type 2 diabetes mellitus: a randomized, double-blind, parallel group comparison trial. Diabet Med. 2005;22(4):399–405
   PubMedGoogle Scholar
• . Hanefeld M, Brunetti P, Schernthaner GH, Matthews DR, Charbonnel BH; Quartet Study Group. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care. 2004;27(1):141–147
   PubMedGoogle Scholar
• . Matthews DR, Charbonnel BH, Hanefeld M, Brunetti P, Schernthaner G. Long-term therapy with addition of pioglitazone to metformin compared with the addition of gliclazide to metformin in patients with type 2 diabetes: arandomized, comparative study. Diabetes Metab Res Rev. 2005;21(2):167–174
   PubMed Web of Science ®Google Scholar
• . Actos [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2007. http://www.fda.gov/Drugs/DrugSafety/Post-marketDrugSafetyInformationforPatientsandProviders/ucm109136. htm. Accessed February 27, 2013
   Google Scholar
• . Cusi K, Consoli A, DeFronzo RA. Metabolic effects of metformin on glucose and lactate metabolism in NIDDM. J Clin Endocrinol Metab. 1996;81(11):4059–1067
   PubMed Web of Science ®Google Scholar
• . Bays H, Mandarino L, DeFronzo RA. Role of the adipocytes, FFA, and ectopic fat in the pathogenesis of type 2 diabetes mellitus: PPAR agonists provide a rational therapeutic approach. J Clin Endocrinol Metab. 2004;89(2):463–478
   PubMed Web of Science ®Google Scholar
• . Bays HE, Gonzalez-Campoy JM, Bray GA, . Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther. 2008;6(3):343–368
   PubMedGoogle Scholar
• . Miyazaki Y, He H, Mandarino LJ, DeFronzo RA. Rosiglitazone improves downstream insulin-receptor signaling in type 2 diabetic patients. Diabetes. 2003;52(8):1943–1950
   PubMedGoogle Scholar
• . Coletta DK, Sriwijitkamol A, Wajcberg E, . Pioglitazone stimulates AMPK signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo. Diabetologia. 2009;52(4):723–732
   PubMedGoogle Scholar
• . Kashyap SR, DeFronzo RA. The insulin resistance syndrome: physiological considerations. Diab Vasc Dis Res. 2007;4(1):13–19
   PubMedGoogle Scholar
• . Kashyap SR, Roman LJ, Lamont J, . Insulin resistance is associated with impaired nitric oxide synthase (NOS) activity in skeletal muscle of type 2 diabetic subjects. J Clin Endocrinol Metab. 2005;90(2):1100–1105
   PubMedGoogle Scholar
• . Montagnani M, Chen H, Barr VA, Quon MJ. Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179). J Biol Chem. 2001;276(32):30392–30398
   PubMed Web of Science ®Google Scholar
• . Bajaj M, DeFronzo RA. Metabolic and molecular basis of insulin resistance. J Nuclear Cardiol. 2003;10(3):311–323
   PubMed Web of Science ®Google Scholar
• . Cusi K, Maezono K, Osman A, . Insulin resistance differentially affects the PI 3-kinase-and MAP kinase-mediated signaling in human muscle. J Clin Invest. 2000;105(3):311–320
   PubMed Web of Science ®Google Scholar
• . Kashyap S, Belfort R, Berria R, . Discordant effects of a chronic physiological increase in plasma FFA on insulin signaling in healthy subjects with or without a family history of type 2 diabetes. Am J Physiol Endocrinol Metab. 2004;287(3):E537–E546
   Google Scholar
• . Pratipanawatr W, Pratipanawatr T, Cusi K, . Skeletal muscle insulin resistance in normoglycemic subjects with a strong family history of type 2 diabetes is associated with decreased insulin-stimulated IRS-1 tyrosine phosphorylation. Diabetes. 2001;50(11):2572–2578
   PubMedGoogle Scholar
• . Rothman DL, Magnusson I, Cline G, . Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA. 1995;92(4):983–987
   PubMedGoogle Scholar
• . Morino K, Petersen KF, Dufour S, . Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest. 2005;115(12):3587–3593
   PubMedGoogle Scholar
• . Krook A, Bjornholm M, Galuska D, . Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Diabetes. 2000;49(2):284–292
   PubMedGoogle Scholar
• . Bouzakri K, Roques M, Gual P, . Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes. Diabetes. 2003;52(6):1319–1325
   PubMedGoogle Scholar
• . Wang CC, Goalstone ML, Draznin B. Molecular mechanisms of insulin resistance that impact cardiovascular biology. Diabetes. 2004;53(11):2735–2740
   PubMedGoogle Scholar
• . Draznin B. Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: the two sides of a coin. Diabetes. 2006;55(8):2392–2397
   PubMed Web of Science ®Google Scholar
• . Hsueh WA, Law RE. Insulin signaling in the arterial wall. Am J Cardiol. 1999;84(1A):21J–24J
   Google Scholar
• . Hanley AJ, Williams K, Stern MP, Haffner SM. Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care. 2002;25(7):1177–1184
   PubMed Web of Science ®Google Scholar
• . Isomaa B, Almgren P, Tuomi T, . Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24(4):683–689
   PubMed Web of Science ®Google Scholar
• . Rutter MK, Meigs JB, Sullivan LM, D'Agostino RB Sr, Wilson PW. Insulin resistance, the metabolic syndrome, and incident cardiovascular events in the Framingham Offspring Study. Diabetes. 2005;54(11):3252–3257
   PubMed Web of Science ®Google Scholar
• . Bonora E, Kiechl S, Willeit J, . Insulin resistance as estimated by homeostasis model assessment predicts incident symptomatic cardiovascular disease in Caucasian subjects from the general population: the Bruneck study. Diabetes Care. 2007;30(2):318–324
   PubMed Web of Science ®Google Scholar
• . Howard G, Bergman R, Wagenknecht LE, . Ability of alternative indices of insulin sensitivity to predict cardiovascular risk: comparison with the “minimal model”. Insulin Resistance Atherosclerosis Study (IRAS) Investigators. Ann Epidemiol. 1998;8(6):358–369
   PubMedGoogle Scholar
• . Erdman E, Dormandy JA, Charbonnel B, ; Proactive Investigators. 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) Study. J Am Coll Cardiol. 2007;49(17):1772–1780
   PubMedGoogle Scholar
• . Miyazaki Y, Mahankali A, Wajcberg E, Bajaj M, Mandarino LJ, DeFronzo RA. Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2004;89(9):4312–4319
   PubMed Web of Science ®Google Scholar
• . Bajaj M, Suraamornkul S, Piper P, . Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetes mellitus. J Clin Endocrinol Metab. 2004;89(1):200–206
   PubMed Web of Science ®Google Scholar
• . Miyazaki Y, Glass L, Triplitt C, . Effect of rosiglitazone on glucose and free fatty acid metabolism in type 2 diabetic patients. Diabetologia. 2001;44(12):2210–2219
   PubMedGoogle Scholar
• . Abdul-Ghani MA, Muller FL, Liu Y, . Deleterious action of FA metabolites on ATP synthesis: possible link between lipotoxicity, mitochondrial dysfunction, and insulin resistance. Am J Physiol Endocrinol Metab. 2008;295(3):E678–E685
   PubMed Web of Science ®Google Scholar
• . Belfort R, Mandarino L, Kashyap S, . Dose response effect of elevated plasma FFA on insulin signaling. Diabetes. 2005;54(6):1640–1648
   PubMed Web of Science ®Google Scholar
• . Bajaj M, Pratipanawatr T, Berria R, . Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes. Diabetes. 2002;51(10):3043–3048
   PubMedGoogle Scholar
• . Kashyap S, Belfort R, Gastaldelli A, . A sustained increase in plasma free fatty acids impairs insulin secretion in non-diabetic subjects genetically predisposed to develop type 2 diabetes. Diabetes. 2003;52(10):2461–2474
   PubMed Web of Science ®Google Scholar
• . Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003;112(12):1785–1788
   PubMed Web of Science ®Google Scholar
• . Yki-Järvinen H. Thiazolidinediones and the liver in humans. Curr Opin Lipidol. 2009;20(6):477–183
   PubMedGoogle Scholar
• . Despre JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis. 1990;10(4):497–511
   PubMedGoogle Scholar
• . Wang YX. PPARs: diverse regulators in energy metabolism and metabolic diseases. Cell Res. 2010;20(2):124–137
   PubMed Web of Science ®Google Scholar
• . Patti ME, Butte AJ, Crunkhorn S, . Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1—and NRF1. Proc Natl Acad Sci USA. 2003;100(14):8466–8471
   PubMed Web of Science ®Google Scholar
• . Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev. 2003;24(1):78–90
   PubMed Web of Science ®Google Scholar
• . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study Group. Lancet. 1988;352(9131):837–853
   Google Scholar
• . Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study. Lancet. 1988;352(9131):854–865
   Google Scholar
• . Brown JB, Conner C, Nichols GA. Secondary failure of metformin monotherapy in clinical practice. Diabetes Care. 2010;33(3):501–506
   PubMed Web of Science ®Google Scholar
• . Xiang AH, Peters RK, Kjos SL, . Effect of pioglitazone on pancreatic beta-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes. 2006;55(2):517–522
   PubMed Web of Science ®Google Scholar
• . Gerstein HC, Yusuf S, Bosch J, ; DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368(9541):1096–1105
   PubMed Web of Science ®Google Scholar
• . Knowler WC, Hamman RF, Edelstein SL, ; Diabetes Prevention Program Research Group. Prevention of type 2 diabetes with troglitazone in the diabetes prevention program. Diabetes. 2005;54(4):1150–1156
   PubMed Web of Science ®Google Scholar
• . Buchanan TA, Xiang AH, Peters RK, . Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes. 2002;51(9):2796–2803
   PubMed Web of Science ®Google Scholar
• . DeFronzo RA, Tripathy D, Schwenke DC, ; for the ACT NOW Study. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011;364(12):1104–1115
   PubMed Web of Science ®Google Scholar
• . Lupi R, Del Guerra S, Marselli L, . Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARgamma in the modulation of insulin secretion. Am J Physiol Endocrinol Metab. 2004;286(4):E560–E567
   Google Scholar
• . Finegood DT, McArthur MD, Kojwang D, . Beta-cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death. Diabetes. 2001;50(5):1021–1029
   PubMed Web of Science ®Google Scholar
• . Masuda K, Okamoto Y, Tsuura Y, . Effects of troglitazone (CS-045) on insulin secretion in isolated rat pancreatic islets and HIT cells: an insulinotropic mechanism distinct from glibenclamide. Diabetologia. 1995;38(1):24–30
   PubMedGoogle Scholar
• . Sarruf DA, Yu F, Nguyen HT, . Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis. Endocrinology. 2008;150(2):707–712
   PubMedGoogle Scholar
• . Miyazaki Y, Mahankali A, Matsuda M, . Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002;87(6):2784–2791
   PubMed Web of Science ®Google Scholar
• . Miyazaki Y, De Filippis E, Bajaj M, . Predictors of improved glycemic control with rosiglitazone therapy in type 2 diabetic patients: a practical approach for the primary care physician. Br J Diabetes Vasc Dis. 2005;5:28–35
   Google Scholar
• . Wilcox R, Bousser MG, Betteridge DJ, ; PROactive Investigators. 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;38(3):865–873
   PubMed Web of Science ®Google Scholar
• . Lineoff 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. J Am Med Assoc. 2007;298(10):1180–1188
   Google Scholar
• . Ryder REJ. Pioglitazone: an agent which reduces stroke, myocardial infarction and death and is also a key component of the modern paradigm for the optimum management of type 2 diabetes. Brit J Diab Vasc Disease. 2011;11(3):113–120
   Google Scholar
• . Schernhaner G, Chilton RJ. Cardiovascular risk and thiazolidinediones—what do meta-analysis really tell us? Diabetes Obes Metab. 2010;12(12):1023–1035
   PubMedGoogle Scholar
• . Goldberg RB, Kendall DM, Deeg M, ; GLAI Study Investigators. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2005;28(7):1547–1554
   PubMed Web of Science ®Google Scholar
• . Zinman B, Harris SB, Neuman J, . Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet. 2010;376(9735):103–111
   PubMed Web of Science ®Google Scholar
• . Beifort R, Harrison SA, Brown K, . A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355(22):2297–2307
   PubMedGoogle Scholar
• . Bajaj M, Suraamornkul S, Pratipanawatr T, . Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes. 2003;52(6):1364–1370
   PubMedGoogle Scholar
• . Aithal GP, Thomas JA, Kaye PV, . Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology. 2008;135(4):1176–1184
   PubMed Web of Science ®Google Scholar
• . Slama L, Lanoy E, Valantin MA, . Effect of pioglitazone on HIV-1-related lipodystrophy: arandomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther. 2008;13(1):67–76
   PubMedGoogle Scholar
• . McCarthy KJ, Routh RE, Shaw W, Walsh K, Welbourne TC, Johnson JH. Troglitazone halts diabetic glomerulosclerosis by blockade of mesangial expansion. Kidney Intl. 2000;58(6):2341–2350
   PubMed Web of Science ®Google Scholar
• . Yoshimoto T, Naruse M, Nishikawa M, . Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats. Am J Physiol. 1997;272(6 pt 1):E989–E996
   Google Scholar
• . Sarafidis PA, Bakris GL. Protection of the kidney by thiazolidinediones: an assessment from bench to bedside. Kidney Int. 2006;70(7):1223–1233
   PubMed Web of Science ®Google Scholar
• . Sarafidis PA, Stafylas PC, Georgianos PI, Saratzis AN, Lasaridis AN. Effect of thiazolidinediones on albuminuria and proteinuria in diabetes: a meta-analysis. Am J Kidney Dis. 2010;55(5):835–847
   PubMed Web of Science ®Google Scholar
• . Miyazaki Y, Cersosimo E, Triplitt C, DeFronzo RA. Rosiglitazone decreases albuminuria in type 2 diabetic patients. Kidney Int. 2007;72(11):1367–1373
   PubMedGoogle Scholar
• . Nag S, Bilous R, Kelly W, Jones S, Roper N, Connolly V. All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Morality study. Diabet Med. 2007;24(1):10–17
   PubMed Web of Science ®Google Scholar
• . Schneider CA, Ferrannini E, DeFronzo R, Schernthaner G, Yates J, Erdmann E. Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease. J Am Soc Nephrol. 2008;19(1):182–187
   PubMedGoogle Scholar
• . Brunelli SM, Thadhani R, Ikizler TA, Feldman HI. Thiazolidinedione use is associated with better survival in hemodialysis patients with non-insulin dependent diabetes. Kidney Intl. 2009;75(9):961–968
   PubMedGoogle Scholar
• . Miyazaki Y, Matsuda M, DeFronzo, RA. Dose-response effect of pioglitazone on insulin sensitivity and insulin secretion in type 2 diabetes mellitus. Diabetes Care. 2002;25(3):517–523
   PubMed Web of Science ®Google Scholar
• . Einhorn D, Rendell M, Rosenzweig J, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo controlled study. Clin Ther. 2000;22(12):1395–1409
   PubMed Web of Science ®Google Scholar
• . Kelly JE, Hans TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care. 1999;22(2):288–293
   PubMed Web of Science ®Google Scholar
• . Bajaj M, Baig R, Suraamornkul S, . Effect of pioglitazone on intramocellular fat metabolism in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95(4):1916–1923
   PubMedGoogle Scholar
• . US Food and Drug Administration. Safety Alert. Actos (pioglitazone). Takeda Pharmaceuticals North America, Inc. March 2007. www.fda.gov/Safety/MedWatch/Safetyinformation/SafetyAlertsforHuman-MedicalProducts/ucml50451.htm. Accessed April 2011
   Google Scholar
• . Betteridge DJ. Thiazolidinediones and fracture risk in patients with type 2 diabetes. Diabet Med. 2011;28(7):759–771
   PubMed Web of Science ®Google Scholar
• . Bodmer M, Meier C, Kraenzlin ME, Meier CR. Risk of fractures with glitazones: a critical review of the evidence to date. Drug Saf. 2009;32(7): 539–547
   PubMed Web of Science ®Google Scholar
• . Nesto RW, Bell D, Bonow RO, . American Heart Association; American Diabetes Association. Thiazolidinedione use, fluid retention, and congestive heart failure; a consensus statement from the American Heart Association and American Diabetes Association. Circulation. 2003;108(23):2941–2948. Charbonnel B, DeFronzo R, Davidson J, ; PROactive Investigators. Pioglitazone use in combination with insulin in the prospective pioglitazone clinical trial in macrovascular events study (PROactive19). J Clin Endocrinol Metab. 2010;95(5):2163–2171
   PubMed Web of Science ®Google Scholar
• . Raskin P, Rendell M, Riddle MC, Dole JF, Freed MI, Rosenstock J; Rosiglitazone Clinical Trials Study Group. A randomized trial of rosiglitazone therapy in patients with inadequately controlled insulin-treated type 2 diabetes. Diabetes Care. 2001;24(7):1226–1232
   PubMed Web of Science ®Google Scholar
• . Hanefeld M, Pfutzner A, Forst T, Kleine I, Fuchs W. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study. Cardiovasc Diabetol. 2011;10:65
   PubMed Web of Science ®Google Scholar
• . Mudaliar S, Chang AR, Henry RR. Thiazolidinediones, peripheral edema, and type 2 diabetes: incidence, pathophysiology, and clinical implications. Endocr Pract. 2003;9(5):406–416
   PubMedGoogle Scholar
• . Guan Y, Hao C, Cha DR, . Thiazolidinediones expand body fluid volume through PPARgamma stimulation of EnaC-mediated renal salt absorption. Nat Med. 2005;11(8):861–866
   PubMed Web of Science ®Google Scholar
• . Singh S, Loke YK, Furberg CD. Thiazolidinediones and heart failure—a teleo-analysis. Diabetes Care. 2007;30(8):2148–2153
   PubMed Web of Science ®Google Scholar
• . Erdmann E, Charbonnel B, Wilcox RG, ; PROactive Investigators. 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;30(11):2773–2778
   PubMed Web of Science ®Google Scholar
• . van der Meer RW, Rijzewijk LK, de Jong HW, . 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;119(15):2069–2077
   PubMed Web of Science ®Google Scholar
• . Sourij H, Zweiker R, Wascher TC. 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;29(5):1039–1045
   PubMedGoogle Scholar
• . Lewis JD, Ferrara A, Peng T, . Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011;34(4):916–922
   PubMed Web of Science ®Google Scholar
• . Ferrara A, Lewis JD, Quesenberry CP Jr, . Cohort study of pioglitazone and cancer incidence in patients with diabetes. Diabetes Care. 2011;34(4):923–929
   PubMed Web of Science ®Google Scholar
• . Betteridge DJ, DeFronzo RA, Chilton RJ. PROactive: time for a critical appraisal. Eur Heart J. 2008;29(8):969–983
   PubMedGoogle Scholar