Retracted: Cardiovascular safety of oral antidiabetic therapy in type 2 diabetes mellitus- review article

P. S. Singh, Sudhir K. Yadav, Himanshu Sharma, Manoj Kumar


The article titled “Cardiovascular safety of oral antidiabetic therapy in type 2 diabetes mellitus- review article” by Singh PS et al., published in International Journal of Research in Medical Sciences 2017;5(5):1742-1750, DOI: is retracted.

After the publication of the above article, one of the authors reported that some part of the text is plagiarized from his similar article published in Cardiovascular Diabetology, Volume 16 (2017), DOI: (Xu J, Rajaratnam R. Cardiovascular safety of non-insulin pharmacotherapy for type 2 diabetes. Cardiovasc Diabetol. 2017 Feb 2;16(1):18. We contacted the author who could not satisfactorily respond to our queries. Since the author could not satisfactorily defend his article and contravened the declaration he made while submitting his manuscript, it was decided to retract the article from International Journal of Research in Medical Sciences and not to consider any manuscript submitted by him in future.


Antidiabetic drugs, Cardiovascular risk, Drug therapy, Oral hypoglycemic drugs, Type 2 diabetes

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Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-59.

Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-72.

Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360(2):129-39.

Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577-89.

Hiatt WR, Kaul S, Smith RJ. The cardiovascular safety of diabetes drugs insights from the rosiglitazone experience. N Engl J Med. 2013;369(14):1285-89.

DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med. 1995;333(9):541-49.

Knowler WC. 10-year follow up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677-86.

Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574-79.

Ahmed FW, Rider R, Glanville M, Narayanan K, Razvi S, Weaver JU et al. Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study. Cardiovasc Diabetol. 2016;15(1):116.

United Kingdom Prospective Diabetes Study. 34: effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes. The Lancet. 1998;352(9131):854-65.

Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011;13(3):221-38.

Saenz A, Fernandez-Esteban I, Mataix A, Ausejo M, Roque M, Moher D. Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;3:CD002966.

Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Changes in labelling for metformin use in patients with type 2 diabetes and heart failure: documented safety outweighs theoretical risks. Open Medicine. 2011;5(1):e33-e34.

Eurich DT, Weir DL, Majumdar SR, Tsuyuki RT, Johnson JA, Tjosvold L, et al. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail. 2013;6(3):395-402.

Kao J, Tobis J, McClelland RL, Heaton MR, Davis BR, Holmes DR Jr, et al. Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. Am J Cardiol. 2004;93(11):1347-50.

Goergen SK, Rumbold G, Compton G, Harris C. Systematic review of current guidelines on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology. 2010;254(1):261-69.

Baerlocher MO, Asch M, Myers A. Five things to know about metformin and intravenous contrast. Can Med Assoc J. 2013;185(1):E78.

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. 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. 2015;38(1):140-49.

Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm-2016 Executive Summary. Endocr Pract. 2016;22(1):84-113.

Sola D, Rossi L, Schianca GPC, Maffioli P, Bigliocca M, Mella R, et al. Sulfonylureas and their use in clinical practice. Archives of Medical Science: AMS. 2015;11(4):840-8.

Proks P, Reimann F, Green N, Gribble F, Ashcroft1et F. Sulfonylurea Stimulation of Insulin Secretion. Diabetes. 2002;51(Supplement 3):368-76.

Hemmingsen B, Schroll JB, Lund SS, Wetterslev J, Gluud C, Vaag A, et al. Sulphonylurea monotherapy for patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2013;4:9008.

United Kingdom Prospective Diabetes Study. 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med. 1998;128(3):165.

Lawrence CL, Rainbow RD, Davies NW, Standen NB. Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal K(ATP) channels. Br J Pharmacol. 2002;136(5):746-52.

American Diabetes Association. A study of the effects of hypoglycemic agents on vascular complications in patients with adult onset diabetes: VI Supplementary report on nonfatal events in patients treated with tolbutamide. Diabetes. 1976;25(12):1129-53.

Garratt KN, Brady PA, Hassinger NL, Grill DE, Terzic A, Holmes DR Jr. Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction. J Am Coll Cardiol. 1999;33(1):119-24.

Simpson SH, Majumdar SR, Tsuyuki RT, Eurich DT, Johnson JA. Dose response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population based cohort study. Can Med Assoc J. 2006;174(2):169-74.

Roumie CL, Hung AM, Greevy RA, Grijalva CG, Liu X, Murff HJ, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2012;157(9):601-10.

Monami M, Genovese S, Mannucci E. Cardiovascular safety of sulfonylu-reas: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2013;15(10):938-53.

Giblett JP, Axell RG, White PA, Clarke SJ, McCormick L, Read PA, et al. Glucagon-like peptide-1 derived cardioprotection does not utilize a KATP-channel dependent pathway: mechanistic insights from human supply and demand ischemia studies. Cardiovasc Diabetol. 2016;15:99.

Simpson SH, Lee J, Choi S, Vandermeer B, Abdelmoneim AS, Featherstone TR. Mortality risk among sulfonylureas: a systematic review and network meta-analysis. Lancet Diabetes Endocrinol. 2015;3(1):43-51.

Azimova K, Juan SZ, Mukherjee D. Cardiovascular safety profile of currently available diabetic drugs. Ochsner J. 2014;14(4):616-32.

Black C, Donnelly P, McIntyre L, Royle PL, Shepherd JP, Thomas S. Meglitinide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;2:4654.

Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, et al. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1463-76.

Schramm TK, Gislason GH, Vaag A, Rasmussen JN, Folke F, Hansen ML, et al. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nation-wide study. Eur Heart J. 2011;32(15):1900-8.

Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardio-vascular disease in type 2 diabetes. Eur Heart J. 2015;36(34):2288-96.

Yki-Jarvinen H. Thiazolidinediones. N Engl J Med. 2004;351(11):1106-18.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457-71.

Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, et al. Rosiglitazone evaluated for cardiovascular outcomes– an interim analysis. N Engl J Med. 2007;357(1):28-38.

Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, et al. Rosiglitazone evaluated for cardiovascular out-comes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 2009;373(9681):2125-35.

Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279-89.

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

Gerstein HC, Yusuf S, Holman RR, Bosch J, Anand S, Avezum A, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368(9541):1096-1105.

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;22(7):77-80.

Krische D. The glitazones: proceed with caution. West J Med. 2000;173(1):54-7.

Kim W, Egan JM. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev. 2008;60(4):470-512.

Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007;298(2):194-206.

Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipepti-dylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther. 2014;5(1):1-41.

Davidson JA. Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. Cleve Clin J Med. 2009;76(Suppl 5):28-38.

Fadini GP, Avogaro A. Cardiovascular effects of DPP-4 inhibition: beyond GLP-1. Vasc Pharmacol. 2011;55(13):10-6.

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317-26.

Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130(18):1579-88.

White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327-35.

Zannad F, Cannon CP, Cushman WC, Bakris GL, Menon V, Perez AT, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAM-INE: a multicentre, randomised, double-blind trial. Lancet. 2015;385(9982):2067-76.

Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015;373(3):232-42.

Nakamura T, Iwanaga Y, Miyaji Y, Nohara R, Ishimura T, Miyazaki S. Cardiovascular efficacy of sitagliptin in patients with diabetes at high risk of cardiovascular disease: a 12-month follow-up. Cardiovasc Diabetol. 2016;15:54-9.

Maruhashi T, Higashi Y, Kihara Y, Yamada H, Sata M, Ueda S et al. Long-term effect of sitagliptin on endothelial function in type 2 diabetes: a sub-analysis of the PROLOGUE study. Cardiovasc Diabetol. 2016;15(1):134-9.

Rosenstock J, Marx N, Neubacher D, Seck T, Patel S, Woerle HJ, et al. Cardiovascular safety of linagliptin in type 2 diabe-tes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol. 2015;14:57.

Li L, Li S, Deng K, Liu J, Vandvik PO, Zhao P, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. BMJ. 2016;352:610.

Filion KB, Azoulay L, Platt RW, Dahl M, Dormuth CR, Clemens KK, et al. A multicenter observational study of incretin-based drugs and heart failure. N Engl J Med. 2016;374(12):1145-54.

Toh S, Hampp C, Reichman ME, Graham DJ, Balakrishnan S, Pucino F, et al. Risk for hospitalized heart failure among new users of saxa-gliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Ann Intern Med. 2016;164(11):705-14.

Ou HT, Chang KC, Li CY, Wu JS. Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: a nation-wide longitudinal study. Cardiovasc Diabetol. 2016;15:41.

Shyangdan DS, Royle P, Clar C, Sharma P, Waugh N, Snaith A. Glucagon-like peptide analogues for type 2 diabe-tes mellitus. Cochrane Database Syst Rev. 2011;10:6423.

Sun F, Wu S, Wang J, Guo S, Chai S, Yang Z, et al. Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes: a systematic review and network meta-analysis. Clin Ther. 2015;37(1):225-41.

Katout M, Zhu H, Rutsky J, Shah P, Brook RD, Zhong J, et al. Effect of GLP-1 mimetics on blood pressure and rela-tionship to weight loss and glycemia lowering: results of a systematic meta-analysis and meta-regression. Am J Hypertens. 2014;27(1):130-39.

Angeli FS, Shannon RP. Incretin-based therapies: can we achieve glyce-mic control and cardioprotection? J Endocrinol. 2014;221(1):17-30.

Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247-57.

Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-22.

Kumarathurai P, Anholm C, Nielsen OW, Kristiansen OP, Molvig J, Madsbad S, et al. Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes: a randomized double-blind placebo-controlled crossover study. Cardiovasc Diabetol. 2016;15(1):105.

Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-44.

Ferdinand KC, Botros FT, Atisso CM, Sager PT, et al. Cardiovascular safety for once-weekly dulaglutide in type 2 diabetes: a pre-specified meta-analysis of prospectively adju-dicated cardiovascular events. Cardiovasc Diabetol. 2016;15:38.

Clar C, Gill JA, Court R, Waugh N. Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open. 2012;2(5):1007.

Hanefeld M, Forst T. Dapagliflozin, an SGLT2 inhibitor, for diabetes. Lancet. 2010;375(9733):2196-98.

Musso G, Gambino R, Cassader M, Pagano G. A novel approach to control hyperglycemia in type 2 dia-betes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med. 2012;44(4):375-93.

Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262-74.

Hasan FM, Alsahli M, Gerich JE. SGLT2 inhibitors in the treatment of type 2 diabetes. Diabetes Res Clin Pract. 2014;104(3):297-322.

Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB, et al. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8(4):262-75.

Oelze M, Kröller-Schön S, Welschof P, Jansen T, Hausding M, Mikhed Y, et al. The sodium glucose co-transporter 2 inhibitor empagliflozin improves diabetes induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS ONE. 2014;9(11):2394.

Fitchett D, Zinman B, Wanner C, Lachin JM, Hantel S, Salsali A, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA REG OUTCOME (R) trial. Eur Heart J. 2016;37(19):1526-34.

Wu JH, Foote C, Blomster J, Toyama T, Perkovic V, Sundström J, et al. Effects of sodium glucose cotransporter-2 inhibitors on cardiovascular events, death and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4(5):411-19.

Roden M, Merker L, Christiansen AV, Roux F, Salsali A, Gabriel Kim G, et al. Safety, tolerability and effects on cardiometabolic risk factors of empagliflozin monotherapy in drug naive patients with type 2 diabetes: a double-blind extension of a Phase III randomized controlled trial. Cardiovasc Diabetol. 2015;14:154-60.

Sonesson C, Johansson PA, Johnsson E, Gause-Nilsson I. Cardiovascular effects of dapagliflozin in patients with type 2 diabetes and different risk categories: a meta-analysis. Cardiovasc Diabetol. 2016;15:37-41.

Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M et al. Acarbose treatment and risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance.the STOP NIDDM trial. JAMA. 2003;290(4):486-90.

Shimabukuro M, Higa M, Yamakawa K, Masuzaki H, Sata M. Migital, alpha glucosidase inhibitor reduces visceral fat accumulation and cardiovascular risk factor in subjects with metabolic syndrome.a randomized comparable study.Int J Cardiol. 2013;167(5):108-13.

Hariya N, Mochizuki K, Inoue S, Saito M, Fuchigami M, Goda T, et al. Switching alpha glucosidase inhibitors to migital reduced glucose fluctuations and circulatory cardiovascular disease risk factors in type2 diabetic Japanese patients. D Drugs RD. 2014;14(3):177-84.

DiNicolantonio JJ, Bhutani J, O’Keefe JH. Acarbose, safe and effective for lowering post prandial hyperglycemia and improving cardiovascular outcome. Open Heart. 2015;2(1):321.