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The current role of thiazolidinediones in diabetes management

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Abstract

Among the epidemics of modern time, type 2 diabetes mellitus (T2DM) is one of the main contributors to overall morbidity as well as mortality. A number of different treatment options are available for the management of diabetes. Among them thiazolidinediones (TZDs) is an interesting drug class since it does not target the result of T2DM, i.e., hyperglycemia but rather some of the core mechanisms of the disease. Indeed, glitazones increase insulin sensitivity by activating the peroxisome proliferator-activated receptor γ, which plays an important role in regulating various metabolic parameters. Although TZDs have an established efficacy in T2DM treatment, their usage during the past years was questioned following the emergence of some alarming data regarding their safety and especially the cardiovascular safety of rosiglitazone. As a result, there is often some skepticism about the current role of TZDs in T2DM management. This mainly affects rosiglitazone even leading to its withdrawal from several markets in contrast to pioglitazone, which has shown a beneficial cardiovascular profile. A comprehensive assessment of the benefit-to-risk ratio of TZDs is required in order to better understand the place of these drugs in T2DM management.

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References

  • Actos Product Information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000285/WC500021386.pdf. Accessed 19 Mar 2016

  • Avandia Product Information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000268/WC500029108.pdf. Accessed 19 Mar 2016

  • Aithal GP, Thomas JA, Kaye PV, Lawson A, Ryder SD, Spendlove I, Austin AS, Freeman JG, Morgan L, Webber J (2008) Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 135:1176–1184

    Article  CAS  PubMed  Google Scholar 

  • Alderman MH, Cohen H, Madhavan S, Kivlighn S (1999) Serum uric acid and cardiovascular events in successfully treated hypertensive patients. Hypertension 34:144–150

    Article  CAS  PubMed  Google Scholar 

  • Ambrosius WT, Danis RP, Goff DC, Greven CM, Gerstein HC, Cohen RM, Riddle MC, Miller ME, Buse JB, Bonds DE, Peterson KA, Rosenberg YD, Perdue LH, Esser BA, Seaquist LA, Felicetta JV, Chew EY, Group AS (2010) Lack of association between thiazolidinediones and macular edema in type 2 diabetes: the ACCORD eye substudy. Arch Ophthalmol 128:312–318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL (2000) Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Diabetes Care 23:1605–1611

    Article  CAS  PubMed  Google Scholar 

  • Atamer Y, Atamer A, Can AS, Hekimoğlu A, Ilhan N, Yenice N, Koçyiğit Y (2013) Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus. Braz J Med Biol Res 46:528–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Athyros VG, Elisaf M, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, Milionis HJ, Mikhailidis DP (2004) Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Am J Kidney Dis 43:589–599

    Article  CAS  PubMed  Google Scholar 

  • Azoulay L, Yin H, Filion KB, Assayag J, Majdan A, Pollak MN, Suissa S (2012) The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case–control study. BMJ 344:e3645

    Article  PubMed  PubMed Central  Google Scholar 

  • Baibergenova A, Walsh S (2012) Use of pioglitazone in patients with lichen planopilaris. J Cutan Med Surg 16:97–100

    CAS  PubMed  Google Scholar 

  • Bakris GL, Ruilope LM, McMorn SO, Weston WM, Heise MA, Freed MI, Porter LE (2006) Rosiglitazone reduces microalbuminuria and blood pressure independently of glycemia in type 2 diabetes patients with microalbuminuria. J Hypertens 24:2047–2055

    Article  CAS  PubMed  Google Scholar 

  • Balaji V, Seshiah V, Ashtalakshmi G, Ramanan SG, Janarthinakani M (2014) A retrospective study on finding correlation of pioglitazone and incidences of bladder cancer in the Indian population. Indian J Endocrinol Metab 18:425–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barbiero JK, Santiago RM, Persike DS, da Silva Fernandes MJ, Tonin FS, da Cunha C, Lucio Boschen S, Lima MM, Vital MA (2014) Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine. Behav Brain Res 274:390–399

    Article  CAS  PubMed  Google Scholar 

  • Bauters C, Lamblin N, Mc Fadden EP, Van Belle E, Millaire A, de Groote P (2003) Influence of diabetes mellitus on heart failure risk and outcome. Cardiovasc Diabetol 2:1

    Article  PubMed  PubMed Central  Google Scholar 

  • Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K (2006) A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 355:2297–2307

    Article  CAS  PubMed  Google Scholar 

  • Bernard S, Serusclat A, Targe F, Charriere S, Roth O, Beaune J, Berthezene F, Moulin P (2005) Incremental predictive value of carotid ultrasonography in the assessment of coronary risk in a cohort of asymptomatic type 2 diabetic subjects. Diabetes Care 28:1158–1162

    Article  PubMed  Google Scholar 

  • Berria R, Glass L, Mahankali A, Miyazaki Y, Monroy A, De Filippis E, Cusi K, Cersosimo E, Defronzo RA, Gastaldelli A (2007) Reduction in hematocrit and hemoglobin following pioglitazone treatment is not hemodilutional in type II diabetes mellitus. Clin Pharmacol Ther 82:275–281

    Article  CAS  PubMed  Google Scholar 

  • Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC Jr (2004) Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care 27:699–703

    Article  PubMed  Google Scholar 

  • Bertrand OF, Poirier P, Rodés-Cabau J, Rinfret S, Title LM, Dzavik V, Natarajan M, Angel J, Batalla N, Alméras N, Costerousse O, De Larochellière R, Roy L, Després J-P, Investigators VT (2010) Cardiometabolic effects of rosiglitazone in patients with type 2 diabetes and coronary artery bypass grafts: a randomized placebo-controlled clinical trial. Atherosclerosis 211:565–573

    Article  CAS  PubMed  Google Scholar 

  • Bhatt DL, Chew DP, Grines C, Mukherjee D, Leesar M, Gilchrist IC, Corbelli JC, Blankenship JC, Eres A, Steinhubl S, Tan WA, Resar JR, AlMahameed A, Abdel-Latif A, Wilson Tang WH, Brennan D, McErlean E, Hazen SL, Topol EJ (2007) Peroxisome proliferator-activated receptor gamma agonists for the prevention of adverse events following percutaneous coronary revascularization—results of the PPAR study. Am Heart J 154:137–143

    Article  CAS  PubMed  Google Scholar 

  • Billington EO, Grey A, Bolland MJ (2015) The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis. Diabetologia 58:2238–2246

    Article  CAS  PubMed  Google Scholar 

  • Boettcher E, Csako G, Pucino F, Wesley R, Loomba R (2012) Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 35:66–75

    Article  CAS  PubMed  Google Scholar 

  • Bone HG, Lindsay R, McClung MR, Perez AT, Raanan MG, Spanheimer RG (2013) 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 98:4691–4701

    Article  CAS  PubMed  Google Scholar 

  • Bosetti C, Rosato V, Buniato D, Zambon A, La Vecchia C, Corrao G (2013) Cancer risk for patients using thiazolidinediones for type 2 diabetes: a meta-analysis. Oncologist 18:148–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bray GA, Smith SR, Banerji MA, Tripathy D, Clement SC, Buchanan TA, Henry RR, Kitabchi AE, Mudaliar S, Musi N, Ratner RE, Schwenke DC, Stentz FB, Reaven PD, DeFronzo RA (2013) Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial. Diabetes Obes Metab 15:931–937

    Article  CAS  PubMed  Google Scholar 

  • Breunig IM, Shaya FT, McPherson ML, Snitker S (2014) Development of heart failure in Medicaid patients with type 2 diabetes treated with pioglitazone, rosiglitazone, or metformin. J Manag Care Spec Pharm 20:895–903

    PubMed  Google Scholar 

  • Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, Park JY, King GL, LoGerfo FW, Horton ES, Veves A (1999) Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes 48:1856–1862

    Article  CAS  PubMed  Google Scholar 

  • Campbell IW, Mariz S (2007) Beta-cell preservation with thiazolidinediones. Diabetes Res Clin Pract 76:163–176

    Article  CAS  PubMed  Google Scholar 

  • Carey DG, Cowin GJ, Galloway GJ, Jones NP, Richards JC, Biswas N, Doddrell DM (2002) Effect of rosiglitazone on insulin sensitivity and body composition in type 2 diabetic patients [corrected]. Obes Res 10:1008–1015

    Article  CAS  PubMed  Google Scholar 

  • Carney GA, Bassett K, Wright JM, Dormuth CR (2012) Is thiazolidinediones use a factor in delaying the need for insulin therapy in type 2 patients with diabetes? A population-based cohort study. BMJ Open 2:e001910

    PubMed  Google Scholar 

  • Carta AR, Simuni T (2015) Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson’s disease. Expert Opin Investig Drugs 24:219–227

    Article  CAS  PubMed  Google Scholar 

  • Chalasani N, Teal E, Hall SD (2005) Effect of rosiglitazone on serum liver biochemistries in diabetic patients with normal and elevated baseline liver enzymes. Am J Gastroenterol 100:1317–1321

    Article  CAS  PubMed  Google Scholar 

  • Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55:2005–2023

    Article  PubMed  Google Scholar 

  • Colmers IN, Bowker SL, Majumdar SR, Johnson JA (2012) Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis. CMAJ 184:E675–E683

    Article  PubMed  PubMed Central  Google Scholar 

  • Colucciello M (2005) Vision loss due to macular edema induced by rosiglitazone treatment of diabetes mellitus. Arch Ophthalmol 123:1273–1275

    Article  PubMed  Google Scholar 

  • Cusi K (2010) The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr Diabetes Rep 10:306–315

    Article  CAS  Google Scholar 

  • Dargie HJ, Hildebrandt PR, Riegger GA, McMurray JJ, McMorn SO, Roberts JN, Zambanini A, Wilding JP (2007) A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association Functional Class I or II Heart Failure. J Am Coll Cardiol 49:1696–1704

    Article  CAS  PubMed  Google Scholar 

  • Daskalopoulou SS, Athyros VG, Elisaf M, Mikhailidis D (2004) The impact of serum uric acid on cardiovascular outcomes in the LIFE study. Kidney Int 66:1714–1715

    Article  PubMed  Google Scholar 

  • Daskalopoulou SS, Tzovaras V, Mikhailidis DP, Elisaf M (2005) Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia. Curr Pharm Des 11:4161–4175

    Article  CAS  PubMed  Google Scholar 

  • DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Hodis HN, Kitabchi AE, Mack WJ, Mudaliar S, Ratner RE, Williams K, Stentz FB, Musi N, Reaven PD, Study AN (2011) Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med 364:1104–1115

    Article  CAS  PubMed  Google Scholar 

  • DeFronzo RA, Chilton R, Norton L, Clarke G, Ryder RE, Abdul-Ghani M (2016) Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor. Diabetes Obes Metab 18:454–462

    Article  CAS  PubMed  Google Scholar 

  • Derosa G, D’Angelo A, Ragonesi PD, Ciccarelli L, Piccinni MN, Pricolo F, Salvadeo SA, Montagna L, Gravina A, Ferrari I, Paniga S, Cicero AF (2006) 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 31:375–383

    Article  CAS  PubMed  Google Scholar 

  • Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, Welty TK, Fabsitz RR, Robbins D, Rhoades ER, Howard BV (2000) Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 101:2271–2276

    Article  CAS  PubMed  Google Scholar 

  • Diamond GA, Bax L, Kaul S (2007) Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Ann Intern Med 147:578–581

    Article  PubMed  Google Scholar 

  • Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J (2005) 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 366:1279–1289

    Article  CAS  PubMed  Google Scholar 

  • Dormandy JA, Betteridge DJ, Schernthaner G, Pirags V, Norgren L, Investigators P (2009) Impact of peripheral arterial disease in patients with diabetes—results from PROactive (PROactive 11). Atherosclerosis 202:272–281

    Article  CAS  PubMed  Google Scholar 

  • DREAM Trial Investigators, Dagenais GR, Gerstein HC, Holman R, Budaj A, Escalante A, Hedner T, Keltai M, Lonn E, McFarlane S, McQueen M, Teo K, Sheridan P, Bosch J, Pogue J, Yusuf S (2008) 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 31:1007–1014

    Article  CAS  Google Scholar 

  • Duncan BB, Schmidt MI, Pankow JS, Bang H, Couper D, Ballantyne CM, Hoogeveen RC, Heiss G (2004) Adiponectin and the development of type 2 diabetes: the Atherosclerosis Risk in Communities Study. Diabetes 53:2473–2478

    Article  CAS  PubMed  Google Scholar 

  • Edelstein SL, Knowler WC, Bain RP, Andres R, Barrett-Connor EL, Dowse GK, Haffner SM, Pettitt DJ, Sorkin JD, Muller DC, Collins VR, Hamman RF (1997) Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies. Diabetes 46:701–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • EMEA (2008) EMEA recommends new warnings and contraindications for rosiglitazone. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500015420.pdf. Accessed 19 Mar 2016

  • EMEA (2010) European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2010/09/WC500096996.pdf. Accessed 19 Mar 2016

  • Erdmann E, Harding S, Lam H, Perez A (2016) Ten-year observational follow-up of PROactive: a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes. Diabetes Obes Metab 18:266–273

    Article  CAS  PubMed  Google Scholar 

  • Esposito K, Ciotola M, Carleo D, Schisano B, Saccomanno F, Sasso FC, Cozzolino D, Assaloni R, Merante D, Ceriello A, Giugliano D (2006) Effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. Diabetes Care 29:1071–1076

    Article  CAS  PubMed  Google Scholar 

  • FDA (2007a) Division of Metabolism and Endocrine Products and Office of Surveillance and Epidemiology, US Food and Drug Administration. FDA Briefing Document: joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. July 30, 2007. http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4308b1-02-fda-backgrounder.pdf. Accessed 19 Mar 2016

  • FDA (2007b) FDA Adds Boxed Warning for Heart-related Risks to Anti-Diabetes Drug Avandia. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109026.htm. Accessed 19 Mar 2016

  • FDA (2013a) FDA requires removal of certain restrictions on the diabetes drug Avandia. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376516.htm. Accessed 19 Mar 2016

  • FDA (2013b) Highlights of prescribing information. Pioglitazone. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf. Accessed 23 Apr 2016

  • FDA (2014) Highlights of prescribing information. Rosiglitazone. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021071s047s048s049lbl.pdf. Accessed 23 Apr 2016

  • Ferrara A, Lewis JD, Quesenberry CP Jr, Peng T, Strom BL, Van Den Eeden SK, Ehrlich SF, Habel LA (2011) Cohort study of pioglitazone and cancer incidence in patients with diabetes. Diabetes Care 34:923–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferris FL III, Patz A (1984) Macular edema. A complication of diabetic retinopathy. Surv Ophthalmol 28(Suppl):452–461

    Article  PubMed  Google Scholar 

  • Florez H, Reaven PD, Bahn G, Moritz T, Warren S, Marks J, Reda D, Duckworth W, Abraira C, Hayward R, Emanuele N, Group VR (2015) Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial. Diabetes Obes Metab 17:949–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fonseca V (2003) Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med 115(Suppl 8A):42S–48S

    Article  CAS  PubMed  Google Scholar 

  • Forman BM, Chen J, Evans RM (1996) The peroxisome proliferator-activated receptors: ligands and activators. Ann NY Acad Sci 804:266–275

    Article  CAS  PubMed  Google Scholar 

  • Fujimoto K, Hamamoto Y, Honjo S, Kawasaki Y, Mori K, Tatsuoka H, Matsuoka A, Wada Y, Ikeda H, Fujikawa J, Koshiyama H (2013) Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 99:e21–e23

    Article  CAS  PubMed  Google Scholar 

  • Gaede P, Vedel P, Larsen N, Jensen GVH, Parving H-H, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393

    Article  PubMed  Google Scholar 

  • Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, Davidson MB, Einhorn D, Garber JR, Garvey WT, Grunberger G, Handelsman Y, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez G, Davidson MH (2015) Aace/Ace comprehensive diabetes management algorithm 2015. Endocr Pract 21:438–447

    Article  PubMed  Google Scholar 

  • Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA (2007) Thiazolidinediones improve beta-cell function in type 2 diabetic patients. Am J Physiol Endocrinol Metab 292:E871–E883

    Article  CAS  PubMed  Google Scholar 

  • Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman RR (2006) Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368:1096–1105

    Article  CAS  PubMed  Google Scholar 

  • GlaxoSmithKline (2006) GlaxoSmithKline clinical trial register: study No. ZM2005/00181/01, Avandia Cardiovascular Event Modeling Project, and study No. HM2006/00497/00/WEUSRTP866, Coronary Heart Disease Outcomes in Patients Receiving Antidiabetic Agents. http://www.gsk-clinicalstudyregister.com/files2/3104.pdf. Accessed 19 Mar 2016

  • Goldberg RB, Kendall DM, Deeg MA, Buse JB, Zagar AJ, Pinaire JA, Tan MH, Khan MA, Perez AT, Jacober SJ (2005) A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 28:1547–1554

    Article  CAS  PubMed  Google Scholar 

  • Graham DJ, Green L, Senior JR, Nourjah P (2003) Troglitazone-induced liver failure: a case study. Am J Med 114:299–306

    Article  PubMed  Google Scholar 

  • Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC, Sowers JR (1999) Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 100:1134–1146

    Article  CAS  PubMed  Google Scholar 

  • Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149

    Article  CAS  PubMed  Google Scholar 

  • Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI (2002) Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 106:679–684

    Article  CAS  PubMed  Google Scholar 

  • Hamdy O, Porramatikul S, Al-Ozairi E (2006) Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev 2:367–373

    Article  PubMed  Google Scholar 

  • He S, Y-h Tang, Zhao G, Yang X, Wang D, Zhang Y (2014) Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis. Tumour Biol 35:2095–2102

    Article  CAS  PubMed  Google Scholar 

  • Helmy MM, Helmy MW, El-Mas MM (2015) Additive renoprotection by pioglitazone and fenofibrate against inflammatory, oxidative and apoptotic manifestations of cisplatin nephrotoxicity: modulation by PPARs. PLoS ONE 10:e0142303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Heneka MT, Fink A, Doblhammer G (2015) Effect of pioglitazone medication on the incidence of dementia. Ann Neurol 78:284–294

    Article  CAS  PubMed  Google Scholar 

  • Hernandez AV, Usmani A, Rajamanickam A, Moheet A (2011) 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 11:115–128

    Article  CAS  PubMed  Google Scholar 

  • Hippisley-Cox J, Coupland C (2016) Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care. BMJ 352:i1450

    Article  PubMed  PubMed Central  Google Scholar 

  • Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ (2007) Rosiglitazone evaluated for cardiovascular outcomes-an interim analysis. N Engl J Med 357:28–38

    Article  CAS  PubMed  Google Scholar 

  • Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJV, Team RS (2009) Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 373:2125–2135

    Article  CAS  PubMed  Google Scholar 

  • Hsiao F-Y, Hsieh P-H, Huang W-F, Tsai Y-W, Gau C-S (2013) Risk of bladder cancer in diabetic patients treated with rosiglitazone or pioglitazone: a nested case–control study. Drug Saf 36:643–649

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Xing H, Dong X, Lu W, Xiao X, Gao L, Cui M, Chen J (2015) Pioglitazone is an effective treatment for patients with post-stroke depression combined with type 2 diabetes mellitus. Exp Ther Med 10:1109–1114

    CAS  PubMed  PubMed Central  Google Scholar 

  • Idris I, Warren G, Donnelly R (2012) Association between thiazolidinedione treatment and risk of macular edema among patients with type 2 diabetes. Arch Intern Med 172:1005–1011

    Article  CAS  PubMed  Google Scholar 

  • International Diabetes Federation, Clinical Guidelines Task Force (2012) Global guideline for type 2 diabetes. http://www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf. Accessed 19 Mar 2016

  • Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR (2015) Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38:140–149

    Article  PubMed  Google Scholar 

  • Jick SS, Stender M, Myers MW (1999) Frequency of liver disease in type 2 diabetic patients treated with oral antidiabetic agents. Diabetes Care 22:2067–2071

    Article  CAS  PubMed  Google Scholar 

  • Jimba S, Nakagami T, Takahashi M, Wakamatsu T, Hirota Y, Iwamoto Y, Wasada T (2005) Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabetes Med 22:1141–1145

    Article  CAS  Google Scholar 

  • Jin S-M, Song SO, Jung CH, Chang J-S, Suh S, Kang SM, Jung I, Park C-Y, Kim JH, Cho JH, Lee B-W (2014) Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study. J Korean Med Sci 29:238–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones NP, Curtis PS, Home PD (2015) Cancer and bone fractures in observational follow-up of the RECORD study. Acta Diabetol 52:539–546

    Article  CAS  PubMed  Google Scholar 

  • Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O’Neill MC, Zinman B, Viberti G (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443

    Article  CAS  PubMed  Google Scholar 

  • Kahn SE, Zinman B, Lachin JM, Haffner SM, Herman WH, Holman RR, Kravitz BG, Yu D, Heise MA, Aftring RP, Viberti G (2008) Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care 31:845–851

    Article  CAS  PubMed  Google Scholar 

  • Kakafika AI, Liberopoulos EN, Karagiannis A, Athyros VG, Mikhailidis DP (2006) Dyslipidaemia, hypercoagulability and the metabolic syndrome. Curr Vasc Pharmacol 4:175–183

    Article  CAS  PubMed  Google Scholar 

  • Kaplan RC, Heckbert SR, Furberg CD, Psaty BM (2002) Predictors of subsequent coronary events, stroke, and death among survivors of first hospitalized myocardial infarction. J Clin Epidemiol 55:654–664

    Article  PubMed  Google Scholar 

  • Kashani L, Omidvar T, Farazmand B, Modabbernia A, Ramzanzadeh F, Tehraninejad ES, Ashrafi M, Tabrizi M, Akhondzadeh S (2013) Does pioglitazone improve depression through insulin-sensitization? Results of a randomized double-blind metformin-controlled trial in patients with polycystic ovarian syndrome and comorbid depression. Psychoneuroendocrinology 38:767–776

    Article  CAS  PubMed  Google Scholar 

  • Kemp DE, Ismail-Beigi F, Ganocy SJ, Conroy C, Gao K, Obral S, Fein E, Findling RL, Calabrese JR (2012) Use of insulin sensitizers for the treatment of major depressive disorder: a pilot study of pioglitazone for major depression accompanied by abdominal obesity. J Affect Disord 136:1164–1173

    Article  CAS  PubMed  Google Scholar 

  • Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP Jr, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O’Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR, Investigators IT (2016) Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 374:1321–1331

    Article  PubMed  Google Scholar 

  • Khanolkar MP, Morris RH, Thomas AW, Bolusani H, Roberts AW, Geen J, Jackson SK, Evans LM (2008) Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus–an effect probably mediated by direct platelet PPARgamma activation. Atherosclerosis 197:718–724

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Kang ES, Kim DJ, Kim SH, Ahn CW, Cha BS, Nam M, Chung CH, Lee KW, Nam CM, Lee HC (2007) Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin-18 is an independent factor for the improvement of homeostasis model assessment-beta in type 2 diabetes mellitus. Clin Endocrinol (Oxf) 66:282–289

    Article  CAS  Google Scholar 

  • Kohler HP (2002) Insulin resistance syndrome: interaction with coagulation and fibrinolysis. Swiss Med Wkly 132:241–252

    PubMed  Google Scholar 

  • Kostapanos MS, Elisaf MS, Mikhailidis DP (2013) Pioglitazone and cancer: angel or demon? Curr Pharm Des 19:4913–4929

    Article  CAS  PubMed  Google Scholar 

  • Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM (1995) Bone loss and bone turnover in diabetes. Diabetes 44:775–782

    Article  CAS  PubMed  Google Scholar 

  • LaBrecque DR, Abbas Z, Anania F, Ferenci P, Khan AG, Goh K-L, Hamid SS, Isakov V, Lizarzabal M, Peñaranda MM, Ramos JFR, Sarin S, Stimac D, Thomson ABR, Umar M, Krabshuis J, LeMair A, Organisation WG (2014) World Gastroenterology Organisation global guidelines: nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol 48:467–473

    PubMed  Google Scholar 

  • Lebovitz HE, Dole JF, Patwardhan R, Rappaport EB, Freed MI (2001) Rosiglitazone monotherapy is effective in patients with type 2 diabetes. J Clin Endocrinol Metab 86:280–288

    Article  CAS  PubMed  Google Scholar 

  • Lecka-Czernik B (2009) Bone as a target of type 2 diabetes treatment. Curr Opin Investig Drugs 10:1085–1090

    CAS  PubMed  Google Scholar 

  • Lee J, Reding M (2007) Effects of thiazolidinediones on stroke recovery: a case-matched controlled study. Neurochem Res 32:635–638

    Article  CAS  PubMed  Google Scholar 

  • Lee M-Y, Hsiao P-J, Yang Y-H, Lin K-D, Shin S-J (2014) The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease. PLoS ONE 9:e85479

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Leiter LA (2005) Beta-cell preservation: a potential role for thiazolidinediones to improve clinical care in type 2 diabetes. Diabetes Med 22:963–972

    Article  CAS  Google Scholar 

  • Levin D, Bell S, Sund R, Hartikainen SA, Tuomilehto J, Pukkala E, Keskimäki I, Badrick E, Renehan AG, Buchan IE, Bowker SL, Minhas-Sandhu JK, Zafari Z, Marra C, Johnson JA, Stricker BH, Uitterlinden AG, Hofman A, Ruiter R, de Keyser CE, MacDonald TM, Wild SH, McKeigue PM, Colhoun HM, Group SDRNE, Diabetes, Consortium CR (2015) Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis. Diabetologia 58:493–504

    Article  CAS  PubMed  Google Scholar 

  • Lewis JD, Ferrara A, Peng T, Hedderson M, Bilker WB, Quesenberry CP, Vaughn DJ, Nessel L, Selby J, Strom BL (2011) Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 34:916–922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis JD, Habel LA, Quesenberry CP, Strom BL, Peng T, Hedderson MM, Ehrlich SF, Mamtani R, Bilker W, Vaughn DJ, Nessel L, Van Den Eeden SK, Ferrara A (2015) Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. JAMA 314:265–277

    Article  CAS  PubMed  Google Scholar 

  • Li R, Xu W, Luo S, Xu H, Tong G, Zeng L, Zhu D, Weng J (2015) Effect of exenatide, insulin and pioglitazone on bone metabolism in patients with newly diagnosed type 2 diabetes. Acta Diabetol 52:1083–1091

    Article  CAS  PubMed  Google Scholar 

  • Lin K-D, Lee M-Y, Feng C-C, Chen BK, Yu M-L, Shin S-J (2014) Residual effect of reductions in red blood cell count and haematocrit and haemoglobin levels after 10-month withdrawal of pioglitazone in patients with type 2 diabetes. Diabetes Med 31:1341–1349

    Article  CAS  Google Scholar 

  • Lincoff AM, Wolski K, Nicholls SJ, Nissen SE (2007) Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 298:1180–1188

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Wang LN (2015) Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack. Cochrane Database Syst Rev 10:CD010693

    PubMed  Google Scholar 

  • Lu Y, Ma D, Xu W, Shao S, Yu X (2015) Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: a meta-analysis. J Diabetes Investig 6:78–86

    Article  CAS  PubMed  Google Scholar 

  • Mackness MI, Durrington PN, Mackness B (2004) The role of paraoxonase 1 activity in cardiovascular disease: potential for therapeutic intervention. Am J Cardiovasc Drugs 4:211–217

    Article  CAS  PubMed  Google Scholar 

  • Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y (2001) PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:2094–2099

    Article  CAS  PubMed  Google Scholar 

  • Makri OE, Georgalas I, Georgakopoulos CD (2013) Drug-induced macular edema. Drugs 73:789–802

    Article  CAS  PubMed  Google Scholar 

  • Mamtani R, Haynes K, Bilker WB, Vaughn DJ, Strom BL, Glanz K, Lewis JD (2012) Association between longer therapy with thiazolidinediones and risk of bladder cancer: a cohort study. J Natl Cancer Inst 104:1411–1421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mamza J, Mehta R, Donnelly R, Idris I (2016) Important differences in the durability of glycaemic response among second-line treatment options when added to metformin in type 2 diabetes: a retrospective cohort study. Ann Med 48:224–234

    Article  CAS  PubMed  Google Scholar 

  • Marcovina SM, Koschinsky ML (1998) Lipoprotein(a) as a risk factor for coronary artery disease. Am J Cardiol 82:57U–66U

    Article  CAS  PubMed  Google Scholar 

  • Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM (2005) Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation 111:583–590

    Article  CAS  PubMed  Google Scholar 

  • Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, D’Agostino RB Sr, Perez A, Provost JC, Haffner SM (2006) Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 296:2572–2581

    Article  CAS  PubMed  Google Scholar 

  • McCullough AJ (2006) Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 40:S17–S29

    CAS  PubMed  Google Scholar 

  • McLaughlin TM, Liu T, Yee G, Abbasi F, Lamendola C, Reaven GM, Tsao P, Cushman SW, Sherman A (2010) Pioglitazone increases the proportion of small cells in human abdominal subcutaneous adipose tissue. Obesity (Silver Spring) 18:926–931

    Article  CAS  Google Scholar 

  • Mendes D, Alves C, Batel-Marques F (2015) Number needed to harm in the post-marketing safety evaluation: results for rosiglitazone and pioglitazone. Pharmacoepidemiol Drug Saf 24:1259–1270

    Article  CAS  PubMed  Google Scholar 

  • Mesinkovska NA, Tellez A, Dawes D, Piliang M, Bergfeld W (2015) The use of oral pioglitazone in the treatment of lichen planopilaris. J Am Acad Dermatol 72:355–356

    Article  PubMed  Google Scholar 

  • Milionis HJ, Kalantzi KJ, Goudevenos JA, Seferiadis K, Mikhailidis DP, Elisaf MS (2005) Serum uric acid levels and risk for acute ischaemic non-embolic stroke in elderly subjects. J Intern Med 258:435–441

    Article  CAS  PubMed  Google Scholar 

  • Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, Mandarino LJ, DeFronzo RA (2002) Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 87:2784–2791

    Article  CAS  PubMed  Google Scholar 

  • Miyazaki Y, Cersosimo E, Triplitt C, DeFronzo RA (2007) Rosiglitazone decreases albuminuria in type 2 diabetic patients. Kidney Int 72:1367–1373

    Article  CAS  PubMed  Google Scholar 

  • Monami M, Lamanna C, Marchionni N, Mannucci E (2008) Rosiglitazone and risk of cancer: a meta-analysis of randomized clinical trials. Diabetes Care 31:1455–1460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monami M, Dicembrini I, Mannucci E (2014) Thiazolidinediones and cancer: results of a meta-analysis of randomized clinical trials. Acta Diabetol 51:91–101

    Article  CAS  PubMed  Google Scholar 

  • Moon JH, Kim HJ, Kim SK, Kang ES, Lee BW, Ahn CW, Lee HC, Cha BS (2011) Fat redistribution preferentially reflects the anti-inflammatory benefits of pioglitazone treatment. Metabolism 60:165–172

    Article  CAS  PubMed  Google Scholar 

  • Morikawa A, Ishizeki K, Iwashima Y, Yokoyama H, Muto E, Oshima E, Sekiguchi M, Miura T, Itoh H, Haneda M (2011) Pioglitazone reduces urinary albumin excretion in renin-angiotensin system inhibitor-treated type 2 diabetic patients with hypertension and microalbuminuria: the APRIME study. Clin Exp Nephrol 15:848–853

    Article  CAS  PubMed  Google Scholar 

  • Negrotto L, Farez MF, Correale J (2016) Immunologic effects of metformin and pioglitazone treatment on metabolic syndrome and multiple sclerosis. JAMA Neurol [Epub ahead of print]

  • Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Le Winter M, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R (2003) Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Circulation 108:2941–2948

    Article  PubMed  Google Scholar 

  • Neumann A, Weill A, Ricordeau P, Fagot JP, Alla F, Allemand H (2012) Pioglitazone and risk of bladder cancer among diabetic patients in France: a population-based cohort study. Diabetologia 55:1953–1962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR (2003) Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 38:1008–1017

    Article  CAS  PubMed  Google Scholar 

  • Nichols GA, Hillier TA, Erbey JR, Brown JB (2001) Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care 24:1614–1619

    Article  CAS  PubMed  Google Scholar 

  • Nilsson PM, Hedblad B, Donaldson J, Berglund G (2007) Rosiglitazone reduces office and diastolic ambulatory blood pressure following 1-year treatment in non-diabetic subjects with insulin resistance. Blood Press 16:95–100

    Article  CAS  PubMed  Google Scholar 

  • NINDS Exploratory Trials in Parkinson Disease (NET-PD) FS-ZONE Investigators (2015) NINDS Exploratory Trials in Parkinson Disease FS-ZONE Investigators. Pioglitazone in early Parkinson’s disease: a phase 2, multicentre, double-blind, randomised trial. Lancet Neurol 14:795–803

    Article  CAS  Google Scholar 

  • Nissen SE, Wolski K (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356:2457–2471

    Article  CAS  PubMed  Google Scholar 

  • Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, Jure H, De Larochellière R, Staniloae CS, Mavromatis K, Saw J, Hu B, Lincoff AM, Tuzcu EM, Investigators P (2008) Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 299:1561–1573

    Article  CAS  PubMed  Google Scholar 

  • Norhammar A, Tenerz A, Nilsson G, Hamsten A, Efendíc S, Rydén L, Malmberg K (2002) Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 359:2140–2144

    Article  CAS  PubMed  Google Scholar 

  • Petrica L, Vlad A, Petrica M, Jianu CD, Gluhovschi G, Gadalean F, Dumitrascu V, Ianculescu C, Firescu C, Giju S, Gluhovschi C, Bob F, Velciov S, Bozdog G, Milas O, Marian R, Ursoniu S (2011) Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus. Diabetes Res Clin Pract 94:22–32

    Article  CAS  PubMed  Google Scholar 

  • Piccinni C, Motola D, Marchesini G, Poluzzi E (2011) Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting. Diabetes Care 34:1369–1371

    Article  PubMed  PubMed Central  Google Scholar 

  • Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, van der Schouw YT, Spencer E, Moons KGM, Tjønneland A, Halkjaer J, Jensen MK, Stegger J, Clavel-Chapelon F, Boutron-Ruault M-C, Chajes V, Linseisen J, Kaaks R, Trichopoulou A, Trichopoulos D, Bamia C, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Peeters PHM, May AM, Bueno-de-Mesquita HB, van Duijnhoven FJB, Hallmans G, Weinehall L, Manjer J, Hedblad B, Lund E, Agudo A, Arriola L, Barricarte A, Navarro C, Martinez C, Quirós JR, Key T, Bingham S, Khaw KT, Boffetta P, Jenab M, Ferrari P, Riboli E (2008) General and abdominal adiposity and risk of death in Europe. N Engl J Med 359:2105–2120

    Article  CAS  PubMed  Google Scholar 

  • Pistrosch F, Herbrig K, Kindel B, Passauer J, Fischer S, Gross P (2005) Rosiglitazone improves glomerular hyperfiltration, renal endothelial dysfunction, and microalbuminuria of incipient diabetic nephropathy in patients. Diabetes 54:2206–2211

    Article  CAS  PubMed  Google Scholar 

  • Pladevall M, Riera-Guardia N, Margulis AV, Varas-Lorenzo C, Calingaert B, Perez-Gutthann S (2016) Cardiovascular risk associated with the use of glitazones, metformin and sufonylureas: meta-analysis of published observational studies. BMC Cardiovasc Disord 16:14

    Article  PubMed  PubMed Central  Google Scholar 

  • Prost S, Relouzat F, Spentchian M, Ouzegdouh Y, Saliba J, Massonnet G, Beressi JP, Verhoeyen E, Raggueneau V, Maneglier B, Castaigne S, Chomienne C, Chretien S, Rousselot P, Leboulch P (2015) Erosion of the chronic myeloid leukaemia stem cell pool by PPARgamma agonists. Nature 525:380–383

    Article  CAS  PubMed  Google Scholar 

  • Psaty BM, Furberg CD (2007) The record on rosiglitazone and the risk of myocardial infarction. N Engl J Med 357:67–69

    Article  CAS  PubMed  Google Scholar 

  • Punthakee Z, Alméras N, Després J-P, Dagenais GR, Anand SS, Hunt DL, Sharma AM, Jung H, Yusuf S, Gerstein HC (2014) Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM trial. Diabetes Med 31:1086–1092

    Article  CAS  Google Scholar 

  • Qin S, Liu T, Kamanna VS, Kashyap ML (2007) Pioglitazone stimulates apolipoprotein A-I production without affecting HDL removal in HepG2 cells: involvement of PPAR-alpha. Arterioscler Thromb Vasc Biol 27:2428–2434

    Article  CAS  PubMed  Google Scholar 

  • Radenković M (2014) Pioglitazone and endothelial dysfunction: pleiotropic effects and possible therapeutic implications. Sci Pharm 82:709–721

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rasgon NL, Kenna HA, Williams KE, Powers B, Wroolie T, Schatzberg AF (2010) Rosiglitazone add-on in treatment of depressed patients with insulin resistance: a pilot study. Sci World J 10:321–328

    Article  CAS  Google Scholar 

  • Riera-Guardia N, Rothenbacher D (2008) The effect of thiazolidinediones on adiponectin serum level: a meta-analysis. Diabetes Obes Metab 10:367–375

    Article  CAS  PubMed  Google Scholar 

  • Rizos CV, Liberopoulos EN, Mikhailidis DP, Elisaf MS (2008) Pleiotropic effects of thiazolidinediones. Expert Opin Pharmacother 9:1087–1108

    Article  CAS  PubMed  Google Scholar 

  • Rizos CV, Elisaf MS, Mikhailidis DP, Liberopoulos EN (2009) How safe is the use of thiazolidinediones in clinical practice? Expert Opin Drug Saf 8:15–32

    Article  CAS  PubMed  Google Scholar 

  • Roughead EE, Chan EW, Choi NK, Kimura M, Kimura T, Kubota K, Lai EC, Man KK, Nguyen TA, Ooba N, Park BJ, Sato T, Shin JY, Wang T, Griffiths J, Wong IC, Yang YH, Pratt NL (2015) Variation in association between thiazolidinediones and heart failure across ethnic groups: retrospective analysis of large healthcare claims databases in six countries. Drug Saf 38:823–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryan EH Jr, Han DP, Ramsay RC, Cantrill HL, Bennett SR, Dev S, Williams DF (2006) Diabetic macular edema associated with glitazone use. Retina 26:562–570

    Article  PubMed  Google Scholar 

  • Saha SA, Kizhakepunnur LG, Bahekar A, Arora RR (2007) The role of fibrates in the prevention of cardiovascular disease—a pooled meta-analysis of long-term randomized placebo-controlled clinical trials. Am Heart J 154:943–953

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto J, Kimura H, Moriyama S, Odaka H, Momose Y, Sugiyama Y, Sawada H (2000) Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem Biophys Res Commun 278:704–711

    Article  CAS  PubMed  Google Scholar 

  • Salmela PI, Sotaniemi EA, Niemi M, Maentausta O (1984) Liver function tests in diabetic patients. Diabetes Care 7:248–254

    Article  CAS  PubMed  Google Scholar 

  • Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR, CRN N (2010) Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362:1675–1685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarafidis PA, Stafylas PC, Georgianos PI, Saratzis AN, Lasaridis AN (2010) Effect of thiazolidinediones on albuminuria and proteinuria in diabetes: a meta-analysis. Am J Kidney Dis 55:835–847

    Article  CAS  PubMed  Google Scholar 

  • Saremi A, Schwenke DC, Buchanan TA, Hodis HN, Mack WJ, Banerji M, Bray GA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Tripathy D, DeFronzo RA, Reaven PD (2013) Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arterioscler Thromb Vasc Biol 33:393–399

    Article  CAS  PubMed  Google Scholar 

  • Schernthaner G, Matthews DR, Charbonnel B, Hanefeld M, Brunetti P, Group QS (2004) Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. J Clin Endocrinol Metab 89:6068–6076

    Article  CAS  PubMed  Google Scholar 

  • Seaquist ER, Miller ME, Fonseca V, Ismail-Beigi F, Launer LJ, Punthakee Z, Sood A (2013) Effect of thiazolidinediones and insulin on cognitive outcomes in ACCORD-MIND. J Diabetes Complicat 27:485–491

    Article  PubMed  PubMed Central  Google Scholar 

  • Seber S, Ucak S, Basat O, Altuntas Y (2006) The effect of dual PPAR alpha/gamma stimulation with combination of rosiglitazone and fenofibrate on metabolic parameters in type 2 diabetic patients. Diabetes Res Clin Pract 71:52–58

    Article  CAS  PubMed  Google Scholar 

  • Shim WS, Do MY, Kim SK, Kim HJ, Hur KY, Kang ES, Ahn CW, Lim SK, Lee HC, Cha BS (2006) The long-term effects of rosiglitazone on serum lipid concentrations and body weight. Clin Endocrinol (Oxf) 65:453–459

    Article  CAS  Google Scholar 

  • Shuster JJ, Jones LS, Salmon DA (2007) Fixed vs random effects meta-analysis in rare event studies: the rosiglitazone link with myocardial infarction and cardiac death. Stat Med 26:4375–4385

    Article  PubMed  Google Scholar 

  • Sidhu JS, Cowan D, Tooze JA, Kaski JC (2004) Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces circulating platelet activity in patients without diabetes mellitus who have coronary artery disease. Am Heart J 147:e25

    Article  PubMed  CAS  Google Scholar 

  • Singh S, Loke YK, Furberg CD (2007) Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 298:1189–1195

    Article  CAS  PubMed  Google Scholar 

  • Smith SC, Haslam D (2007) Abdominal obesity, waist circumference and cardio-metabolic risk: awareness among primary care physicians, the general population and patients at risk—the Shape of the Nations survey. Curr Med Res Opin 23:29–47

    Article  PubMed  Google Scholar 

  • Song SO, Kim KJ, Lee B-W, Kang ES, Cha BS, Lee HC (2012) The risk of bladder cancer in korean diabetic subjects treated with pioglitazone. Diabetes Metab J 36:371–378

    Article  PubMed  PubMed Central  Google Scholar 

  • Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228

    Article  CAS  PubMed  Google Scholar 

  • St John Sutton M, Rendell M, Dandona P, Dole JF, Murphy K, Patwardhan R, Patel J, Freed M (2002) A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care 25:2058–2064

    Article  PubMed  Google Scholar 

  • Stabile G, Borrielli I, Artenisio AC, Bruno LM, Benvenga S, Giunta L, La Marca A, Volpe A, Pizzo A (2014) Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome. J Pediatr Adolesc Gynecol 27:177–182

    Article  PubMed  Google Scholar 

  • Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD (1996) Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 97:2601–2610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stevens JW, Khunti K, Harvey R, Johnson M, Preston L, Woods HB, Davies M, Goyder E (2015) Preventing the progression to type 2 diabetes mellitus in adults at high risk: a systematic review and network meta-analysis of lifestyle, pharmacological and surgical interventions. Diabetes Res Clin Pract 107:320–331

    Article  CAS  PubMed  Google Scholar 

  • Stone JC, Furuya-Kanamori L, Barendregt JJ, Doi SA (2015) Was there really any evidence that rosiglitazone increased the risk of myocardial infarction or death from cardiovascular causes? Pharmacoepidemiol Drug Saf 24:223–227

    Article  CAS  PubMed  Google Scholar 

  • Straznicky NE, Grima MT, Sari CI, Eikelis N, Lambert GW, Nestel PJ, Karapanagiotidis S, Wong C, Richards K, Marusic P, Dixon JB, Schlaich MP, Lambert EA (2014) A randomized controlled trial of the effects of pioglitazone treatment on sympathetic nervous system activity and cardiovascular function in obese subjects with metabolic syndrome. J Clin Endocrinol Metab 99:E1701–E1707

    Article  CAS  PubMed  Google Scholar 

  • Suh S, Seo GH, Jung CH, Kim M-K, Jin S-M, Hwang Y-C, Lee B-W, Kim JH (2015) Increased risk of hospitalization for heart failure with newly prescribed dipeptidyl peptidase-4 inhibitors and pioglitazone using the korean health insurance claims database. Diabetes Metab J 39:247–252

    Article  PubMed  PubMed Central  Google Scholar 

  • Tan MH, Baksi A, Krahulec B, Kubalski P, Stankiewicz A, Urquhart R, Edwards G, Johns D, Group GS (2005) Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care 28:544–550

    Article  CAS  PubMed  Google Scholar 

  • Tanaka R, Yamashiro K, Okuma Y, Shimura H, Nakamura S, Ueno Y, Tanaka Y, Miyamoto N, Tomizawa Y, Nakahara T, Furukawa Y, Watada H, Kawamori R, Hattori N, Urabe T (2015) Effects of pioglitazone for secondary stroke prevention in patients with impaired glucose tolerance and newly diagnosed diabetes: the J-SPIRIT study. J Atheroscler Thromb 22:1305–1316

    Article  CAS  PubMed  Google Scholar 

  • Tatti P, Arrigoni F, Longobardi A, Costanza F, Di Blasi P, Merante D (2008) Retrospective analysis of rosiglitazone and macular oedema in patients with type 2 diabetes mellitus. Clin Drug Investig 28:327–332

    Article  CAS  PubMed  Google Scholar 

  • Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Kitabchi AE, Mudaliar S, Ratner RE, Stentz FB, Musi N, Reaven PD, DeFronzo RA (2016) Diabetes incidence and glucose tolerance after termination of pioglitazone therapy: results from ACT NOW. J Clin Endocrinol Metab [Epub ahead of print]

  • Tseng C-H (2012) Pioglitazone and bladder cancer: a population-based study of Taiwanese. Diabetes Care 35:278–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tseng C-H (2015) Rosiglitazone may reduce non-melanoma skin cancer risk in Taiwanese. BMC Cancer 15:41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tuccori M, Filion KB, Yin H, Yu OH, Platt RW, Azoulay L (2016) Pioglitazone use and risk of bladder cancer: population based cohort study. BMJ 352:i1541

    Article  PubMed  PubMed Central  Google Scholar 

  • Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M, Group FDPS (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350

    Article  CAS  PubMed  Google Scholar 

  • Turner RM, Kwok CS, Chen-Turner C, Maduakor CA, Singh S, Loke YK (2014) Thiazolidinediones and associated risk of bladder cancer: a systematic review and meta-analysis. Br J Clin Pharmacol 78:258–273

    Article  CAS  PubMed  Google Scholar 

  • Vallarino C, Perez A, Fusco G, Liang H, Bron M, Manne S, Joseph G, Yu S (2013) Comparing pioglitazone to insulin with respect to cancer, cardiovascular and bone fracture endpoints, using propensity score weights. Clin Drug Investig 33:621–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes-a meta-analysis. Osteoporos Int 18:427–444

    Article  CAS  PubMed  Google Scholar 

  • Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL (2001) Platelet dysfunction in type 2 diabetes. Diabetes Care 24:1476–1485

    Article  CAS  PubMed  Google Scholar 

  • Wannamethee SG, Lowe GD, Rumley A, Cherry L, Whincup PH, Sattar N (2007) Adipokines and risk of type 2 diabetes in older men. Diabetes Care 30:1200–1205

    Article  CAS  PubMed  Google Scholar 

  • Watanabe S, Hashimoto E, Ikejima K, Uto H, Ono M, Sumida Y, Seike M, Takei Y, Takehara T, Tokushige K, Nakajima A, Yoneda M, Saibara T, Shiota G, Sakaida I, Nakamuta M, Mizuta T, Tsubouchi H, Sugano K, Shimosegawa T, Gastroenterology JSo, Hepatology JSo (2015) Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. J Gastroenterol 50:364–377

    Article  PubMed  Google Scholar 

  • Wei L, MacDonald TM, Mackenzie IS (2013) Pioglitazone and bladder cancer: a propensity score matched cohort study. Br J Clin Pharmacol 75:254–259

    Article  CAS  PubMed  Google Scholar 

  • Wilcox R, Bousser MG, Betteridge DJ, Schernthaner G, Pirags V, Kupfer S, Dormandy J (2007) 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 38:865–873

    Article  CAS  PubMed  Google Scholar 

  • Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, Ochoa C, Kawakubo M, Buchanan TA (2006) Effect of pioglitazone on pancreatic beta-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes 55:517–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu W, Bi Y, Sun Z, Li J, Guo L, Yang T, Wu G, Shi L, Feng Z, Qiu L, Li Q, Guo X, Luo Z, Lu J, Shan Z, Yang W, Ji Q, Yan L, Li H, Yu X, Li S, Zhou Z, Lv X, Liang Z, Lin S, Zeng L, Yan J, Ji L, Weng J (2015) Comparison of the effects on glycaemic control and β-cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel-group trial (the CONFIDENCE study). J Intern Med 277:137–150

    Article  CAS  PubMed  Google Scholar 

  • Yaturu S, Bryant B, Jain SK (2007) Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care 30:1574–1576

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama H, Araki S, Kawai K, Hirao K, Oishi M, Sugimoto K, Sone H, Maegawa H, Kashiwagi A, Group JDCDMS (2015) Pioglitazone treatment and cardiovascular event and death in subjects with type 2 diabetes without established cardiovascular disease (JDDM 36). Diabetes Res Clin Pract 109:485–492

    Article  CAS  PubMed  Google Scholar 

  • Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, Olefsky JM (2002) The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51:2968–2974

    Article  CAS  PubMed  Google Scholar 

  • Zanchi A, Tappy L, Le KA, Bortolotti M, Theumann N, Halabi G, Gauthier T, Mathieu C, Tremblay S, Bertrand PC, Burnier M, Teta D (2014) Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study. PLoS ONE 9:e109134

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu ZN, Jiang YF, Ding T (2014) Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone 68:115–123

    Article  CAS  PubMed  Google Scholar 

  • Zinman B, Harris SB, Neuman J, Gerstein HC, Retnakaran RR, Raboud J, Qi Y, Hanley AJG (2010) Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet 376:103–111

    Article  CAS  PubMed  Google Scholar 

  • Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE, Investigators E-RO (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117–2128

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Moses S. Elisaf.

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This review was written independently; no company or institution supported it financially. Some of the authors have given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies.

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Rizos, C.V., Kei, A. & Elisaf, M.S. The current role of thiazolidinediones in diabetes management. Arch Toxicol 90, 1861–1881 (2016). https://doi.org/10.1007/s00204-016-1737-4

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