The current role of thiazolidinediones in diabetes management

Archives of Toxicology

Volumn 90, Issue 8, 2016, Pages 1861-1881

  Rizos, Christos V ^a   Kei, Anastazia ^a   Elisaf, Moses S ^a  

^a UNIVERSITY OF IOANNINA   (Greece)

Author keywords

Cardiovascular effects; Diabetes mellitus; Efficacy; Pioglitazone; Pleiotropic effects; Rosiglitazone; Safety; Thiazolidinediones

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; EMPAGLIFLOZIN; METFORMIN; PIOGLITAZONE; ROSIGLITAZONE; SULFONYLUREA; ANTIDIABETIC AGENT; GLUCOSE BLOOD LEVEL;

ANEMIA; ATHEROSCLEROSIS; BLADDER CANCER; CANCER INCIDENCE; CARDIOVASCULAR EFFECT; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; DIABETES CONTROL; DIABETES MELLITUS; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; EDEMA; FRACTURE; HEART FAILURE; HEART INFARCTION; HUMAN; HYPERGLYCEMIA; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; KIDNEY FUNCTION; LIPID STORAGE; LIVER FUNCTION; MACULAR EDEMA; MALIGNANT NEOPLASTIC DISEASE; MENTAL DISEASE; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS ISLET BETA CELL; PLEIOTROPY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK BENEFIT ANALYSIS; RISK REDUCTION; SIDE EFFECT; TREATMENT OUTCOME; WEIGHT GAIN; BLADDER TUMOR; CARDIOVASCULAR DISEASE; CHEMICALLY INDUCED; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; LIVER; METABOLISM; PATHOLOGY; RISK;

BLOOD GLUCOSE; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; FRACTURES, BONE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; LIVER; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK; THIAZOLIDINEDIONES; URINARY BLADDER NEOPLASMS;

EID: 84966668415     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-016-1737-4     Document Type: Review

References (211)

1. Actos Product Information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000285/WC500021386.pdf. Accessed 19 Mar 2016
2. Avandia Product Information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000268/WC500029108.pdf. Accessed 19 Mar 2016
3. 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
4. Alderman MH, Cohen H, Madhavan S, Kivlighn S (1999) Serum uric acid and cardiovascular events in successfully treated hypertensive patients. Hypertension 34:144–150
5. 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
6. 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
7. 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
8. 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
9. 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
10. Baibergenova A, Walsh S (2012) Use of pioglitazone in patients with lichen planopilaris. J Cutan Med Surg 16:97–100
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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
25. 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
26. 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
27. 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
28. Campbell IW, Mariz S (2007) Beta-cell preservation with thiazolidinediones. Diabetes Res Clin Pract 76:163–176
29. 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
30. 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
31. 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
32. 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
33. 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
34. 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
35. Colucciello M (2005) Vision loss due to macular edema induced by rosiglitazone treatment of diabetes mellitus. Arch Ophthalmol 123:1273–1275
36. Cusi K (2010) The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr Diabetes Rep 10:306–315
37. 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
38. 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
39. 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
40. 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
41. 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
42. 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
43. 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
44. 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
45. 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
46. 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
47. 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
48. 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
49. 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
50. 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
51. 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
52. 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
53. 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
54. 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
55. 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
56. 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
57. FDA (2013b) Highlights of prescribing information. Pioglitazone. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf. Accessed 23 Apr 2016
58. FDA (2014) Highlights of prescribing information. Rosiglitazone. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021071s047s048s049lbl.pdf. Accessed 23 Apr 2016
59. 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
60. Ferris FL III, Patz A (1984) Macular edema. A complication of diabetic retinopathy. Surv Ophthalmol 28(Suppl):452–461
61. 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
62. Fonseca V (2003) Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med 115(Suppl 8A):42S–48S
63. Forman BM, Chen J, Evans RM (1996) The peroxisome proliferator-activated receptors: ligands and activators. Ann NY Acad Sci 804:266–275
64. 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
65. 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
66. 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
67. 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
68. 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
69. 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
70. 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
71. Graham DJ, Green L, Senior JR, Nourjah P (2003) Troglitazone-induced liver failure: a case study. Am J Med 114:299–306
72. 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
73. 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
74. 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
75. Hamdy O, Porramatikul S, Al-Ozairi E (2006) Metabolic obesity: the paradox between visceral and subcutaneous fat. Curr Diabetes Rev 2:367–373
76. 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
77. 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
78. Heneka MT, Fink A, Doblhammer G (2015) Effect of pioglitazone medication on the incidence of dementia. Ann Neurol 78:284–294
79. 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
80. 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
81. 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
82. 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
83. 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
84. 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
85. 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
86. 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
87. 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
88. 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
89. 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
90. 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
91. Jones NP, Curtis PS, Home PD (2015) Cancer and bone fractures in observational follow-up of the RECORD study. Acta Diabetol 52:539–546
92. 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
93. 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
94. 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
95. Kakafika AI, Liberopoulos EN, Karagiannis A, Athyros VG, Mikhailidis DP (2006) Dyslipidaemia, hypercoagulability and the metabolic syndrome. Curr Vasc Pharmacol 4:175–183
96. 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
97. 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
98. 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
99. 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
100. 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
101. 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
102. Kohler HP (2002) Insulin resistance syndrome: interaction with coagulation and fibrinolysis. Swiss Med Wkly 132:241–252
103. Kostapanos MS, Elisaf MS, Mikhailidis DP (2013) Pioglitazone and cancer: angel or demon? Curr Pharm Des 19:4913–4929
104. Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM (1995) Bone loss and bone turnover in diabetes. Diabetes 44:775–782
105. 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
106. 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
107. Lecka-Czernik B (2009) Bone as a target of type 2 diabetes treatment. Curr Opin Investig Drugs 10:1085–1090
108. Lee J, Reding M (2007) Effects of thiazolidinediones on stroke recovery: a case-matched controlled study. Neurochem Res 32:635–638
109. 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
110. Leiter LA (2005) Beta-cell preservation: a potential role for thiazolidinediones to improve clinical care in type 2 diabetes. Diabetes Med 22:963–972
111. 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
112. 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
113. 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
114. 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
115. 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
116. 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
117. 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
118. 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
119. 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
120. 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
121. Makri OE, Georgalas I, Georgakopoulos CD (2013) Drug-induced macular edema. Drugs 73:789–802
122. 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
123. 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
124. Marcovina SM, Koschinsky ML (1998) Lipoprotein(a) as a risk factor for coronary artery disease. Am J Cardiol 82:57U–66U
125. 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
126. 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
127. McCullough AJ (2006) Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 40:S17–S29
128. 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
129. 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
130. 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
131. 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
132. 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
133. Miyazaki Y, Cersosimo E, Triplitt C, DeFronzo RA (2007) Rosiglitazone decreases albuminuria in type 2 diabetic patients. Kidney Int 72:1367–1373
134. 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
135. Monami M, Dicembrini I, Mannucci E (2014) Thiazolidinediones and cancer: results of a meta-analysis of randomized clinical trials. Acta Diabetol 51:91–101
136. 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
137. 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
138. 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]
139. 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
140. 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
141. 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
142. 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
143. 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
144. 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
145. 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
146. 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
147. 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
148. 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
149. 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
150. 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
151. 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
152. 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
153. 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
154. Psaty BM, Furberg CD (2007) The record on rosiglitazone and the risk of myocardial infarction. N Engl J Med 357:67–69
155. 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
156. 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
157. Radenković M (2014) Pioglitazone and endothelial dysfunction: pleiotropic effects and possible therapeutic implications. Sci Pharm 82:709–721
158. 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
159. Riera-Guardia N, Rothenbacher D (2008) The effect of thiazolidinediones on adiponectin serum level: a meta-analysis. Diabetes Obes Metab 10:367–375
160. Rizos CV, Liberopoulos EN, Mikhailidis DP, Elisaf MS (2008) Pleiotropic effects of thiazolidinediones. Expert Opin Pharmacother 9:1087–1108
161. 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
162. 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
163. 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
164. 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
165. 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
166. Salmela PI, Sotaniemi EA, Niemi M, Maentausta O (1984) Liver function tests in diabetic patients. Diabetes Care 7:248–254
167. 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
168. 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
169. 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
170. 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
171. 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
172. 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
173. 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
174. 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
175. 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
176. Singh S, Loke YK, Furberg CD (2007) Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 298:1189–1195
177. 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
178. 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
179. 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
180. 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
181. 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
182. 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
183. 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
184. 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
185. 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
186. 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
187. 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
188. 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
189. 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
190. 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]
191. Tseng C-H (2012) Pioglitazone and bladder cancer: a population-based study of Taiwanese. Diabetes Care 35:278–280
192. Tseng C-H (2015) Rosiglitazone may reduce non-melanoma skin cancer risk in Taiwanese. BMC Cancer 15:41
193. 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
194. 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
195. 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
196. 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
197. 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
198. Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL (2001) Platelet dysfunction in type 2 diabetes. Diabetes Care 24:1476–1485
199. 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
200. 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
201. Wei L, MacDonald TM, Mackenzie IS (2013) Pioglitazone and bladder cancer: a propensity score matched cohort study. Br J Clin Pharmacol 75:254–259
202. 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
203. 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
204. 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
205. Yaturu S, Bryant B, Jain SK (2007) Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care 30:1574–1576
206. 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
207. 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
208. 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
209. Zhu ZN, Jiang YF, Ding T (2014) Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials. Bone 68:115–123
210. 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
211. 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