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Current Drug Safety

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ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

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Review Article

Cardiovascular Effects of Hypoglycemic Agents in Diabetes Mellitus

Author(s): Anna Pietraszek*

Volume 16, Issue 1, 2021

Published on: 02 September, 2020

Page: [32 - 51] Pages: 20

DOI: 10.2174/1574886315666200902154736

Price: $65

Abstract

Background: Despite substantial improvements over the years, diabetes mellitus is still associated with cardiovascular disease, heart failure, and excess mortality.

Objective: The objective of this article is to examine existing data on the reduction of cardiovascular morbidity and mortality in diabetes. Control of glycemia, lipid levels, and blood pressure are described in brief. The main scope of this article is, however, to review the glucose-independent cardiovascular effect of antidiabetic pharmacological agents (mainly other than insulin).

Methods: The article is a narrative review based on recently published reviews and meta-analyses complemented with data from individual trials, when relevant.

Results and Discussion: Older data suggest a cardioprotective role of metformin (an inexpensive and safe drug); a role to date not convincingly challenged. The cardiovascular effects of thiazolidinediones, sulphonylurea, and glinides are debatable. Recent large-scale cardiovascular outcome trials suggest a neutral profile of dipeptidyl peptidase 4 inhibitors, yet provide compelling evidence of cardioprotective effects of glucagon-like 1 receptor antagonists and sodium-glucose transporter 2 inhibitors.

Conclusion: Metformin may have a role in primary and secondary prevention of cardiovascular disease; glucagon-like 1 receptor antagonists and sodium-glucose co-transporter 2 inhibitors play a role in secondary prevention of atherosclerotic cardiovascular disease. Sodium-glucose transporter 2 inhibitors have a role to play in both primary and secondary prevention of heart failure; yet, they carry a small risk of the potentially dangerous adverse effect, euglycemic diabetic ketoacidosis.

Keywords: Metformin, antidiabetic, cardioprotection, glinides, glycaemia, sulphonylurea.

« Previous Next »
[1]
Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract 2019; 157: 107843.
[http://dx.doi.org/10.1016/j.diabres.2019.107843] [PMID: 31518657]
[2]
Global Health Estimates 2016: Disease burden by Cause, Age, Sex, by Country and by Region, 2000-2016 World Health Organization 2016.
[3]
Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375(9733): 2215-22.
[http://dx.doi.org/10.1016/S0140-6736(10)60484-9] [PMID: 20609967]
[4]
Franco OH, Steyerberg EW, Hu FB, Mackenbach J, Nusselder W. Associations of diabetes mellitus with total life expectancy and life expectancy with and without cardiovascular disease. Arch Intern Med 2007; 167(11): 1145-51.
[http://dx.doi.org/10.1001/archinte.167.11.1145] [PMID: 17563022]
[5]
Lind M, Garcia-Rodriguez LA, Booth GL, et al. Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study. Diabetologia 2013; 56(12): 2601-8.
[http://dx.doi.org/10.1007/s00125-013-3063-1] [PMID: 24114114]
[6]
Lind M, Svensson AM, Kosiborod M, et al. Glycemic control and excess mortality in type 1 diabetes. N Engl J Med 2014; 371(21): 1972-82.
[http://dx.doi.org/10.1056/NEJMoa1408214] [PMID: 25409370]
[7]
Rawshani A, Rawshani A, Gudbjörnsdottir S. Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes. N Engl J Med 2017; 377(3): 300-1.
[http://dx.doi.org/10.1056/NEJMc1706292] [PMID: 28723317]
[8]
Rawshani A, Sattar N, Franzén S, et al. Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 2018; 392(10146): 477-86.
[http://dx.doi.org/10.1016/S0140-6736(18)31506-X] [PMID: 30129464]
[9]
Tancredi M, Rosengren A, Svensson AM, et al. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med 2015; 373(18): 1720-32.
[http://dx.doi.org/10.1056/NEJMoa1504347] [PMID: 26510021]
[10]
Alva ML, Hoerger TJ, Zhang P, Cheng YJ. State-level diabetes-attributable mortality and years of life lost in the United States. Ann Epidemiol 2018; 28(11): 790-5.
[http://dx.doi.org/10.1016/j.annepidem.2018.08.015] [PMID: 30245053]
[11]
Cavender MA, Steg PG, Smith SC Jr, et al. Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death: Outcomes at 4 Years From the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Circulation 2015; 132(10): 923-31.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.014796] [PMID: 26152709]
[12]
Granger CB, Califf RM, Young S, et al. Outcome of patients with diabetes mellitus and acute myocardial infarction treated with thrombolytic agents. J Am Coll Cardiol 1993; 21(4): 920-5.
[http://dx.doi.org/10.1016/0735-1097(93)90348-5] [PMID: 8450161]
[13]
Rana JS, Liu JY, Moffet HH, Jaffe M, Karter AJ. Diabetes and Prior Coronary Heart Disease are Not Necessarily Risk Equivalent for Future Coronary Heart Disease Events. J Gen Intern Med 2016; 31(4): 387-93.
[http://dx.doi.org/10.1007/s11606-015-3556-3] [PMID: 26666660]
[14]
Dinesh Shah A, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of a wide range of cardiovascular diseases: a cohort study in 1·9 million people. Lancet 2015; 385(Suppl. 1): S86.
[http://dx.doi.org/10.1016/S0140-6736(15)60401-9] [PMID: 26312908]
[15]
Dauriz M, Targher G, Laroche C, et al. Association Between Diabetes and 1-Year Adverse Clinical Outcomes in a Multinational Cohort of Ambulatory Patients With Chronic Heart Failure: Results From the ESC-HFA Heart Failure Long-Term Registry. Diabetes Care 2017; 40(5): 671-8.
[http://dx.doi.org/10.2337/dc16-2016] [PMID: 28255009]
[16]
Targher G, Dauriz M, Laroche C, et al. In-hospital and 1-year mortality associated with diabetes in patients with acute heart failure: results from the ESC-HFA Heart Failure Long-Term Registry. Eur J Heart Fail 2017; 19(1): 54-65.
[http://dx.doi.org/10.1002/ejhf.679] [PMID: 27790816]
[17]
Davies MJ, D’Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41(12): 2669-701.
[http://dx.doi.org/10.2337/dci18-0033] [PMID: 30291106]
[18]
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41(2): 255-323.
[http://dx.doi.org/10.1093/eurheartj/ehz486] [PMID: 31497854]
[19]
Rawshani A, Rawshani A, Franzén S, et al. Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2018; 379(7): 633-44.
[http://dx.doi.org/10.1056/NEJMoa1800256] [PMID: 30110583]
[20]
Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015: a systematic analysis from the Global Burden of Disease Study 2015. Lancet 2017; 389(10082): 1885-906.
[http://dx.doi.org/10.1016/S0140-6736(17)30819-X] [PMID: 28390697]
[21]
Sluik D, Buijsse B, Muckelbauer R, et al. Physical Activity and Mortality in Individuals With Diabetes Mellitus: A Prospective Study and Meta-analysis. Arch Intern Med 2012; 172(17): 1285-95.
[http://dx.doi.org/10.1001/archinternmed.2012.3130] [PMID: 22868663]
[22]
Estruch R, Ros E, Salas-Salvadó J, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med 2018; 378(25): e34.
[http://dx.doi.org/10.1056/NEJMoa1800389] [PMID: 29897866]
[23]
Tuomilehto J, Lindström J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344(18): 1343-50.
[http://dx.doi.org/10.1056/NEJM200105033441801] [PMID: 11333990]
[24]
Lean ME, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 2018; 391(10120): 541-51.
[http://dx.doi.org/10.1016/S0140-6736(17)33102-1] [PMID: 29221645]
[25]
Wing RR, Bolin P, Brancati FL, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369(2): 145-54.
[http://dx.doi.org/10.1056/NEJMoa1212914] [PMID: 23796131]
[26]
Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321(7258): 405-12.
[http://dx.doi.org/10.1136/bmj.321.7258.405] [PMID: 10938048]
[27]
UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance. Diabetologia 1991; 34(12): 877-90.
[http://dx.doi.org/10.1007/BF00400195] [PMID: 1778353]
[28]
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.
[http://dx.doi.org/10.1056/NEJMoa0806470] [PMID: 18784090]
[29]
Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009; 360(2): 129-39.
[http://dx.doi.org/10.1056/NEJMoa0808431] [PMID: 19092145]
[30]
Reaven PD, Emanuele NV, Wiitala WL, et al. Intensive Glucose Control in Patients with Type 2 Diabetes - 15-Year Follow-up. N Engl J Med 2019; 380(23): 2215-24.
[http://dx.doi.org/10.1056/NEJMoa1806802] [PMID: 31167051]
[31]
Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358(24): 2560-72.
[http://dx.doi.org/10.1056/NEJMoa0802987] [PMID: 18539916]
[32]
Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med 2014; 371(15): 1392-406.
[http://dx.doi.org/10.1056/NEJMoa1407963] [PMID: 25234206]
[33]
Buse JB, Bigger JT, Byington RP, et al. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol 2007; 99(12A): 21i-33i.
[http://dx.doi.org/10.1016/j.amjcard.2007.03.003] [PMID: 17599422]
[34]
Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358(24): 2545-59.
[http://dx.doi.org/10.1056/NEJMoa0802743] [PMID: 18539917]
[35]
ACCORD Study Group. Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes. Diabetes Care 2016; 39(5): 701-8.
[http://dx.doi.org/10.2337/dc15-2283] [PMID: 26822326]
[36]
Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009; 52(11): 2288-98.
[http://dx.doi.org/10.1007/s00125-009-1470-0] [PMID: 19655124]
[37]
Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366(9493): 1279-89.
[http://dx.doi.org/10.1016/S0140-6736(05)67528-9] [PMID: 16214598]
[38]
Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995; 26(1): 57-65.
[http://dx.doi.org/10.1016/0735-1097(95)00126-K] [PMID: 7797776]
[39]
Malmberg K. Role of insulin-glucose infusion in outcomes after acute myocardial infarction: the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists Endocr Pract 2004; 10(Suppl12): 13-6.
[40]
Malmberg K, Rydén L, Wedel H, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005; 26(7): 650-61.
[http://dx.doi.org/10.1093/eurheartj/ehi199] [PMID: 15728645]
[41]
Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 2011; 364(9): 829-41.
[http://dx.doi.org/10.1056/NEJMoa1008862] [PMID: 21366474]
[42]
Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995; 75(14): 894-903.
[http://dx.doi.org/10.1016/S0002-9149(99)80683-3] [PMID: 7732997]
[43]
Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353(25): 2643-53.
[http://dx.doi.org/10.1056/NEJMoa052187] [PMID: 16371630]
[44]
Soedamah-Muthu SS, Chaturvedi N, Witte DR, Stevens LK, Porta M, Fuller JH. Relationship between risk factors and mortality in type 1 diabetic patients in Europe: the EURODIAB Prospective Complications Study (PCS). Diabetes Care 2008; 31(7): 1360-6.
[http://dx.doi.org/10.2337/dc08-0107] [PMID: 18375412]
[45]
Shankar A, Klein R, Klein BE, Moss SE. Association between glycosylated hemoglobin level and cardiovascular and all-cause mortality in type 1 diabetes. Am J Epidemiol 2007; 166(4): 393-402.
[http://dx.doi.org/10.1093/aje/kwm096] [PMID: 17526864]
[46]
Chen YT, Vaccarino V, Williams CS, Butler J, Berkman LF, Krumholz HM. Risk factors for heart failure in the elderly: a prospective community-based study. Am J Med 1999; 106(6): 605-12.
[http://dx.doi.org/10.1016/S0002-9343(99)00126-6] [PMID: 10378616]
[47]
Kristensen SL, Preiss D, Jhund PS, et al. PARADIGM-HF Investigators and Committees. Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial. Circ Heart Fail 2016; 9(1): e002560.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002560] [PMID: 26754626]
[48]
Mihaylova B, Emberson J, Blackwell L, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 2012; 380(9841): 581-90.
[http://dx.doi.org/10.1016/S0140-6736(12)60367-5] [PMID: 22607822]
[49]
Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008; 371(9607): 117-25.
[http://dx.doi.org/10.1016/S0140-6736(08)60104-X] [PMID: 18191683]
[50]
Giugliano RP, Cannon CP, Blazing MA, et al. IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) Investigators. Benefit of Adding Ezetimibe to Statin Therapy on Cardiovascular Outcomes and Safety in Patients With Versus Without Diabetes Mellitus: Results From improve-it (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation 2018; 137(15): 1571-82.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.030950] [PMID: 29263150]
[51]
Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol 2017; 5(12): 941-50.
[http://dx.doi.org/10.1016/S2213-8587(17)30313-3] [PMID: 28927706]
[52]
Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015; 313(6): 603-15.
[http://dx.doi.org/10.1001/jama.2014.18574] [PMID: 25668264]
[53]
Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348(5): 383-93.
[http://dx.doi.org/10.1056/NEJMoa021778] [PMID: 12556541]
[54]
Gæde P, Oellgaard J, Carstensen B, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016; 59(11): 2298-307.
[http://dx.doi.org/10.1007/s00125-016-4065-6] [PMID: 27531506]
[55]
Oellgaard J, Gæde P, Rossing P, et al. Reduced risk of heart failure with intensified multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: 21 years of follow-up in the randomised Steno-2 study. Diabetologia 2018; 61(8): 1724-33.
[http://dx.doi.org/10.1007/s00125-018-4642-y] [PMID: 29850922]
[56]
Rawshani A, Rawshani A, Sattar N, et al. Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus. Circulation 2019; 139(16): 1900-12.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037454] [PMID: 30798638]
[57]
Gyberg V, De Bacquer D, De Backer G, et al. EUROASPIRE Investigators. Patients with coronary artery disease and diabetes need improved management: a report from the EUROASPIRE IV survey: a registry from the EuroObservational Research Programme of the European Society of Cardiology. Cardiovasc Diabetol 2015; 14: 133.
[http://dx.doi.org/10.1186/s12933-015-0296-y] [PMID: 26427624]
[58]
Bailey CJ. Metformin: historical overview. Diabetologia 2017; 60(9): 1566-76.
[http://dx.doi.org/10.1007/s00125-017-4318-z] [PMID: 28776081]
[59]
DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 1995; 333(9): 541-9.
[http://dx.doi.org/10.1056/NEJM199508313330902] [PMID: 7623902]
[60]
Jenkins AJ, Welsh P, Petrie JR. Metformin, lipids and atherosclerosis prevention. Curr Opin Lipidol 2018; 29(4): 346-53.
[http://dx.doi.org/10.1097/MOL.0000000000000532] [PMID: 29878903]
[61]
Golay A. Metformin and body weight International journal of obesity 2008; 32(1): 61-72.
[http://dx.doi.org/10.1038/sj.ijo.0803695]
[62]
Assan R, Heuclin C, Girard JR, LeMaire F, Attali JR. Phenformin-induced lactic acidosis in diabetic patients. Diabetes 1975; 24(9): 791-800.
[http://dx.doi.org/10.2337/diab.24.9.791] [PMID: 808437]
[63]
UK Electronic Medicines Compendium (EMC). 2020.https://www.medicines.org.uk/emc
[64]
Crandall JP. Metformin and vitamin B12-What’s missing from this picture? J Diabetes Complications 2018; 32(2): 129.
[http://dx.doi.org/10.1016/j.jdiacomp.2017.11.003] [PMID: 29175118]
[65]
Lalau JD. Lactic acidosis induced by metformin: incidence, management and prevention. Drug Saf 2010; 33(9): 727-40.
[http://dx.doi.org/10.2165/11536790-000000000-00000] [PMID: 20701406]
[66]
Cryer DR, Nicholas SP, Henry DH, Mills DJ, Stadel BV. Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study. Diabetes Care 2005; 28(3): 539-43.
[http://dx.doi.org/10.2337/diacare.28.3.539] [PMID: 15735184]
[67]
Rachmani R, Slavachevski I, Levi Z, Zadok B, Kedar Y, Ravid M. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med 2002; 13(7): 428.
[http://dx.doi.org/10.1016/S0953-6205(02)00131-0] [PMID: 12384131]
[68]
Stang M, Wysowski DK, Butler-Jones D. Incidence of lactic acidosis in metformin users. Diabetes Care 1999; 22(6): 925-7.
[http://dx.doi.org/10.2337/diacare.22.6.925] [PMID: 10372243]
[69]
Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010; (4): CD002967.
[http://dx.doi.org/10.1002/14651858.CD002967.pub3] [PMID: 20393934]
[70]
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352(9131): 854-65.
[http://dx.doi.org/10.1016/S0140-6736(98)07037-8] [PMID: 9742977]
[71]
Turner R. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352(9131): 837-53.
[http://dx.doi.org/10.1016/S0140-6736(98)07019-6] [PMID: 9742976]
[72]
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.
[http://dx.doi.org/10.1002/14651858.CD002966.pub3] [PMID: 16034881]
[73]
Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med 2009; 169(6): 616-25.
[http://dx.doi.org/10.1001/archinternmed.2009.20] [PMID: 19307526]
[74]
Boussageon R, Supper I, Bejan-Angoulvant T, et al. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med 2012; 9(4): e1001204.
[http://dx.doi.org/10.1371/journal.pmed.1001204] [PMID: 22509138]
[75]
Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia 2017; 60(9): 1620-9.
[http://dx.doi.org/10.1007/s00125-017-4337-9] [PMID: 28770324]
[76]
Roussel R, Travert F, Pasquet B, et al. Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med 2010; 170(21): 1892-9.
[http://dx.doi.org/10.1001/archinternmed.2010.409] [PMID: 21098347]
[77]
Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006; 295(2): 180-9.
[http://dx.doi.org/10.1001/jama.295.2.180] [PMID: 16403930]
[78]
Han Y, Xie H, Liu Y, Gao P, Yang X, Shen Z. Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis. Cardiovasc Diabetol 2019; 18(1): 96.
[http://dx.doi.org/10.1186/s12933-019-0900-7] [PMID: 31362743]
[79]
Petrie JR, Chaturvedi N, Ford I, et al. REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2017; 5(8): 597-609.
[http://dx.doi.org/10.1016/S2213-8587(17)30194-8] [PMID: 28615149]
[80]
Eurich DT, Majumdar SR, McAlister FA, Tsuyuki RT, Johnson JA. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care 2005; 28(10): 2345-51.
[http://dx.doi.org/10.2337/diacare.28.10.2345] [PMID: 16186261]
[81]
MacDonald MR, Eurich DT, Majumdar SR, et al. Treatment of type 2 diabetes and outcomes in patients with heart failure: a nested case-control study from the U.K. General Practice Research Database. Diabetes Care 2010; 33(6): 1213-8.
[http://dx.doi.org/10.2337/dc09-2227] [PMID: 20299488]
[82]
Shah DD, Fonarow GC, Horwich TB. Metformin therapy and outcomes in patients with advanced systolic heart failure and diabetes. J Card Fail 2010; 16(3): 200-6.
[http://dx.doi.org/10.1016/j.cardfail.2009.10.022] [PMID: 20206893]
[83]
Nanjan MJ, Mohammed M, Prashantha Kumar BR, Chandrasekar MJN. Thiazolidinediones as antidiabetic agents: A critical review. Bioorg Chem 2018; 77: 548-67.
[http://dx.doi.org/10.1016/j.bioorg.2018.02.009] [PMID: 29475164]
[84]
Cai X, Gao X, Yang W, Han X, Ji L. Efficacy and Safety of Initial Combination Therapy in Treatment-Naïve Type 2 Diabetes Patients: A Systematic Review and Meta-analysis. Diabetes Ther 2018; 9(5): 1995-2014.
[http://dx.doi.org/10.1007/s13300-018-0493-2] [PMID: 30155646]
[85]
Liao HW, Saver JL, Wu YL, Chen TH, Lee M, Ovbiagele B. Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis. BMJ Open 2017; 7(1): e013927.
[http://dx.doi.org/10.1136/bmjopen-2016-013927] [PMID: 28057658]
[86]
Lebovitz HE. Thiazolidinediones: the Forgotten Diabetes Medications. Curr Diab Rep 2019; 19(12): 151.
[http://dx.doi.org/10.1007/s11892-019-1270-y] [PMID: 31776781]
[87]
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.
[http://dx.doi.org/10.1056/NEJMoa072761] [PMID: 17517853]
[88]
Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 2007; 298(10): 1189-95.
[http://dx.doi.org/10.1001/jama.298.10.1189] [PMID: 17848653]
[89]
Home PD, Pocock SJ, Beck-Nielsen H, et al. RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009; 373(9681): 2125-35.
[http://dx.doi.org/10.1016/S0140-6736(09)60953-3] [PMID: 19501900]
[90]
Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 2010; 170(14): 1191-201.
[http://dx.doi.org/10.1001/archinternmed.2010.207] [PMID: 20656674]
[91]
Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA 2010; 304(4): 411-8.
[http://dx.doi.org/10.1001/jama.2010.920] [PMID: 20584880]
[92]
European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim 2010.
[93]
Stone JC, Furuya-Kanamori L, Barendregt JJ, Doi SA. Was there really any evidence that rosiglitazone increased the risk of myocardial infarction or death from cardiovascular causes? Pharmacoepidemiol Drug Saf 2015; 24(3): 223-7.
[http://dx.doi.org/10.1002/pds.3736] [PMID: 25515780]
[94]
de Jong M, van der Worp HB, van der Graaf Y, Visseren FLJ, Westerink J. Pioglitazone and the secondary prevention of cardiovascular disease. A meta-analysis of randomized-controlled trials. Cardiovasc Diabetol 2017; 16(1): 134.
[http://dx.doi.org/10.1186/s12933-017-0617-4] [PMID: 29037211]
[95]
Lv W, Wang X, Xu Q, Lu W. Mechanisms and Characteristics of Sulfonylureas and Glinides. Curr Top Med Chem 2020; 20(1): 37-56.
[http://dx.doi.org/10.2174/1568026620666191224141617] [PMID: 31884929]
[96]
Hirst JA, Farmer AJ, Dyar A, Lung TW, Stevens RJ. Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis. Diabetologia 2013; 56(5): 973-84.
[http://dx.doi.org/10.1007/s00125-013-2856-6] [PMID: 23494446]
[97]
Grenet G, Ribault S, Nguyen GB, et al. GLUcose COntrol Safety & Efficacy in type 2 DIabetes, a systematic review and NETwork meta-analysis. PLoS One 2019; 14(6): e0217701.
[http://dx.doi.org/10.1371/journal.pone.0217701] [PMID: 31237921]
[98]
Bell DSH. Do sulfonylurea drugs increase the risk of cardiac events? 2006; 174(2): 185-6.
[http://dx.doi.org/10.1503/cmaj.051237]
[99]
Meinert CL, Knatterud GL, Prout TE, Klimt CR. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes 1970; 19(Suppl.): 789-830.
[PMID: 4926376]
[100]
Schwartz TB, Meinert CL. The UGDP controversy: thirty-four years of contentious ambiguity laid to rest. Perspect Biol Med 2004; 47(4): 564-74.
[http://dx.doi.org/10.1353/pbm.2004.0071] [PMID: 15467178]
[101]
Bain S, Druyts E, Balijepalli C, et al. Cardiovascular events and all-cause mortality associated with sulphonylureas compared with other antihyperglycaemic drugs: A Bayesian meta-analysis of survival data. Diabetes Obes Metab 2017; 19(3): 329-35.
[http://dx.doi.org/10.1111/dom.12821] [PMID: 27862902]
[102]
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.
[http://dx.doi.org/10.1016/S2213-8587(14)70213-X] [PMID: 25466239]
[103]
Nassif ME, Kosiborod M. A Review of Cardiovascular Outcomes Trials of Glucose-Lowering Therapies and Their Effects on Heart Failure Outcomes. Am J Cardiol 2019; 124(Suppl. 1): S12-9.
[http://dx.doi.org/10.1016/j.amjcard.2019.10.025] [PMID: 31741435]
[104]
Vaccaro O, Masulli M, Nicolucci A, et al. Thiazolidinediones Or Sulfonylureas Cardiovascular Accidents Intervention Trial (TOSCA.IT) study group; Italian Diabetes Society. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial. Lancet Diabetes Endocrinol 2017; 5(11): 887-97.
[http://dx.doi.org/10.1016/S2213-8587(17)30317-0] [PMID: 28917544]
[105]
Holst JJ, Vilsbøll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 2009; 297(1-2): 127-36.
[http://dx.doi.org/10.1016/j.mce.2008.08.012] [PMID: 18786605]
[106]
Andersen A, Lund A, Knop FK, Vilsbøll T. Glucagon-like peptide 1 in health and disease. Nat Rev Endocrinol 2018; 14(7): 390-403.
[http://dx.doi.org/10.1038/s41574-018-0016-2] [PMID: 29728598]
[107]
New Drugs for Type 2 Diabetes: Second-Line Therapy — Science Report Ottawa, ON Canadian Agency for Drugs and Technologies in Health. 2017.
[108]
Liu X, Xiao Q, Zhang L, et al. The long-term efficacy and safety of DPP-IV inhibitors monotherapy and in combination with metformin in 18,980 patients with type-2 diabetes mellitus--a meta-analysis. Pharmacoepidemiol Drug Saf 2014; 23(7): 687-98.
[http://dx.doi.org/10.1002/pds.3586] [PMID: 24639059]
[109]
Abd El Aziz M, Cahyadi O, Meier JJ, Schmidt WE, Nauck MA. Incretin-based glucose-lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based on cardiovascular outcomes trials. Diabetes Obes Metab 2019.
[PMID: 31750601]
[110]
Alfayez OM, Almutairi AR, Aldosari A, Al Yami MS. Update on Cardiovascular Safety of Incretin-Based Therapy in Adults With Type 2 Diabetes Mellitus: A Meta-Analysis of Cardiovascular Outcome Trials. Can J Diabetes 2019; 43(7): 538-545.e2.
[http://dx.doi.org/10.1016/j.jcjd.2019.04.003] [PMID: 31175007]
[111]
Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369(14): 1317-26.
[http://dx.doi.org/10.1056/NEJMoa1307684] [PMID: 23992601]
[112]
Green JB, Bethel MA, Armstrong PW, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2015; 373(3): 232-42.
[http://dx.doi.org/10.1056/NEJMoa1501352] [PMID: 26052984]
[113]
Rosenstock J, Perkovic V, Johansen OE, et al. CARMELINA Investigators. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The carmelina randomized Clinical Trial. JAMA 2019; 321(1): 69-79.
[http://dx.doi.org/10.1001/jama.2018.18269] [PMID: 30418475]
[114]
White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369(14): 1327-35.
[http://dx.doi.org/10.1056/NEJMoa1305889] [PMID: 23992602]
[115]
Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet 2015; 385(9982): 2067-76.
[http://dx.doi.org/10.1016/S0140-6736(14)62225-X] [PMID: 25765696]
[116]
Food U, Administration D. FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin 2016.
[117]
Williams R, de Vries F, Kothny W, et al. Cardiovascular safety of vildagliptin in patients with type 2 diabetes: A European multi-database, non-interventional post-authorization safety study. Diabetes Obes Metab 2017; 19(10): 1473-8.
[http://dx.doi.org/10.1111/dom.12951] [PMID: 28338281]
[118]
Htike ZZ, Zaccardi F, Papamargaritis D, Webb DR, Khunti K, Davies MJ. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab 2017; 19(4): 524-36.
[http://dx.doi.org/10.1111/dom.12849] [PMID: 27981757]
[119]
Coon SA, Crannage EF, Kerwin LC, Guyton JE. Semaglutide once-weekly: improved efficacy with a new safety warning. Expert Rev Clin Pharmacol 2018; 11(11): 1061-72.
[http://dx.doi.org/10.1080/17512433.2018.1534201] [PMID: 30296182]
[120]
Maiorino MI, Chiodini P, Bellastella G, et al. The good companions: insulin and glucagon-like peptide-1 receptor agonist in type 2 diabetes. A systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract 2019; 154: 101-15.
[http://dx.doi.org/10.1016/j.diabres.2019.06.009] [PMID: 31238059]
[121]
Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs--FDA and EMA assessment. N Engl J Med 2014; 370(9): 794-7.
[http://dx.doi.org/10.1056/NEJMp1314078] [PMID: 24571751]
[122]
Monami M, Nreu B, Scatena A, et al. Safety issues with glucagon-like peptide-1 receptor agonists (pancreatitis, pancreatic cancer and cholelithiasis): Data from randomized controlled trials. Diabetes Obes Metab 2017; 19(9): 1233-41.
[http://dx.doi.org/10.1111/dom.12926] [PMID: 28244632]
[123]
Marso SP, Bain SC, Consoli A, et al. SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375(19): 1834-44.
[http://dx.doi.org/10.1056/NEJMoa1607141] [PMID: 27633186]
[124]
Husain M, Birkenfeld AL, Donsmark M, et al. PIONEER 6 Investigators. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2019; 381(9): 841-51.
[http://dx.doi.org/10.1056/NEJMoa1901118] [PMID: 31185157]
[125]
Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol 2019; 7(10): 776-85.
[http://dx.doi.org/10.1016/S2213-8587(19)30249-9] [PMID: 31422062]
[126]
Giugliano D, Maiorino MI, Bellastella G, Longo M, Chiodini P, Esposito K. GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials. Diabetes Obes Metab 2019; 21(11): 2576-80.
[http://dx.doi.org/10.1111/dom.13847] [PMID: 31373167]
[127]
Pfeffer MA, Claggett B, Diaz R, et al. ELIXA Investigators. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med 2015; 373(23): 2247-57.
[http://dx.doi.org/10.1056/NEJMoa1509225] [PMID: 26630143]
[128]
Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER Steering Committee LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375(4): 311-22.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[129]
Holman RR, Bethel MA, Mentz RJ, et al. EXSCEL Study Group. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377(13): 1228-39.
[http://dx.doi.org/10.1056/NEJMoa1612917] [PMID: 28910237]
[130]
Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 2018; 392(10157): 1519-29.
[http://dx.doi.org/10.1016/S0140-6736(18)32261-X] [PMID: 30291013]
[131]
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019; 394(10193): 121-30.
[http://dx.doi.org/10.1016/S0140-6736(19)31149-3] [PMID: 31189511]
[132]
Pulipati VP, Ravi V, Pulipati P. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Eur J Prev Cardiol 2020; 2047487320903638.
[http://dx.doi.org/10.1177/2047487320903638] [PMID: 32089007]
[133]
Marsico F, Paolillo S, Gargiulo P, et al. Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials. Eur Heart J 2020; ehaa082.
[http://dx.doi.org/10.1093/eurheartj/ehaa082] [PMID: 32077924]
[134]
Margulies KB, Hernandez AF, Redfield MM, et al. NHLBI Heart Failure Clinical Research Network. Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA 2016; 316(5): 500-8.
[http://dx.doi.org/10.1001/jama.2016.10260] [PMID: 27483064]
[135]
Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail 2017; 19(1): 69-77.
[http://dx.doi.org/10.1002/ejhf.657] [PMID: 27790809]
[136]
Wang W, Liu H, Xiao S, Liu S, Li X, Yu P. Effects of Insulin Plus Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in Treating Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Diabetes Ther 2017; 8(4): 727-38.
[http://dx.doi.org/10.1007/s13300-017-0282-3] [PMID: 28616805]
[137]
Ahrén B, Hirsch IB, Pieber TR, et al. ADJUNCT TWO Investigators. Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial. Diabetes Care 2016; 39(10): 1693-701.
[http://dx.doi.org/10.2337/dc16-0690] [PMID: 27493132]
[138]
Mathieu C, Zinman B, Hemmingsson JU, et al. ADJUNCT ONE Investigators. Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes Care 2016; 39(10): 1702-10.
[http://dx.doi.org/10.2337/dc16-0691] [PMID: 27506222]
[139]
Storgaard H, Gluud LL, Bennett C, et al. Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. PLoS One 2016; 11(11): e0166125.
[http://dx.doi.org/10.1371/journal.pone.0166125] [PMID: 27835680]
[140]
Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393(10166): 31-9.
[http://dx.doi.org/10.1016/S0140-6736(18)32590-X] [PMID: 30424892]
[141]
Liu J, Li L, Li S, et al. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep 2017; 7(1): 2824.
[http://dx.doi.org/10.1038/s41598-017-02733-w] [PMID: 28588220]
[142]
Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373(22): 2117-28.
[http://dx.doi.org/10.1056/NEJMoa1504720] [PMID: 26378978]
[143]
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377(7): 644-57.
[http://dx.doi.org/10.1056/NEJMoa1611925] [PMID: 28605608]
[144]
Perkovic V, Jardine MJ, Neal B, et al. CREDENCE Trial Investigators. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med 2019; 380(24): 2295-306.
[http://dx.doi.org/10.1056/NEJMoa1811744] [PMID: 30990260]
[145]
Wiviott SD, Raz I, Bonaca MP, et al. DECLARE–TIMI 58 Investigators. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380(4): 347-57.
[http://dx.doi.org/10.1056/NEJMoa1812389] [PMID: 30415602]
[146]
Mahaffey KW, Neal B, Perkovic V, et al. CANVAS Program Collaborative Group. Canagliflozin for Primary and Secondary Prevention of Cardiovascular Events: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation 2018; 137(4): 323-34.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032038] [PMID: 29133604]
[147]
Zinman B, Inzucchi SE, Lachin JM, et al. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol 2014; 13: 102.
[http://dx.doi.org/10.1186/1475-2840-13-102] [PMID: 24943000]
[148]
Kosiborod M, Cavender MA, Fu AZ, et al. CVD-REAL Investigators and Study Group*. Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). Circulation 2017; 136(3): 249-59.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029190] [PMID: 28522450]
[149]
Kosiborod M, Lam CSP, Kohsaka S, et al. CVD-REAL Investigators and Study Group. Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study. J Am Coll Cardiol 2018; 71(23): 2628-39.
[http://dx.doi.org/10.1016/j.jacc.2018.03.009] [PMID: 29540325]
[150]
McMurray JJV, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail 2019; 21(5): 665-75.
[http://dx.doi.org/10.1002/ejhf.1432] [PMID: 30895697]
[151]
McMurray JJV, DeMets DL, Inzucchi SE, et al. DAPA-HF Committees and Investigators. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail 2019; 21(11): 1402-11.
[http://dx.doi.org/10.1002/ejhf.1548] [PMID: 31309699]
[152]
McMurray JJV, Solomon SD, Inzucchi SE, et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381(21): 1995-2008.
[http://dx.doi.org/10.1056/NEJMoa1911303] [PMID: 31535829]
[153]
Anker SD, Butler J, Filippatos GS, et al. Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial. Eur J Heart Fail 2019; 21(10): 1279-87.
[http://dx.doi.org/10.1002/ejhf.1596] [PMID: 31523904]
[154]
Packer M, Butler J, Filippatos GS, et al. EMPEROR-Reduced Trial Committees and Investigators. Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-Reduced trial. Eur J Heart Fail 2019; 21(10): 1270-8.
[http://dx.doi.org/10.1002/ejhf.1536] [PMID: 31584231]
[155]
Peters AL, Henry RR, Thakkar P, Tong C, Alba M. Diabetic Ketoacidosis With Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, in Patients With Type 1 Diabetes. Diabetes Care 2016; 39(4): 532-8.
[http://dx.doi.org/10.2337/dc15-1995] [PMID: 26989182]
[156]
Henry RR, Thakkar P, Tong C, Polidori D, Alba M. Efficacy and Safety of Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes. Diabetes Care 2015; 38(12): 2258-65.
[http://dx.doi.org/10.2337/dc15-1730] [PMID: 26486192]
[157]
Paik J, Blair HA. Dapagliflozin: A Review in Type 1 Diabetes. Drugs 2019; 79(17): 1877-84.
[http://dx.doi.org/10.1007/s40265-019-01213-x] [PMID: 31664708]
[158]
Dandona P, Mathieu C, Phillip M, et al. DEPICT-1 Investigators. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes: The DEPICT-1 52-Week Study. Diabetes Care 2018; 41(12): 2552-9.
[http://dx.doi.org/10.2337/dc18-1087] [PMID: 30352894]
[159]
Mathieu C, Van Den Mooter L, Eeckhout B. Empagliflozin in type 1 diabetes. Diabetes Metab Syndr Obes 2019; 12: 1555-61.
[http://dx.doi.org/10.2147/DMSO.S194688] [PMID: 31686876]
[160]
Mathieu C, Dandona P, Gillard P, et al. DEPICT-2 Investigators. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care 2018; 41(9): 1938-46.
[http://dx.doi.org/10.2337/dc18-0623] [PMID: 30026335]
[161]
Pieber TR, Famulla S, Eilbracht J, et al. Empagliflozin as adjunct to insulin in patients with type 1 diabetes: a 4-week, randomized, placebo-controlled trial (EASE-1). Diabetes Obes Metab 2015; 17(10): 928-35.
[http://dx.doi.org/10.1111/dom.12494] [PMID: 26080652]
[162]
Rosenstock J, Marquard J, Laffel LM, et al. Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials. Diabetes Care 2018; 41(12): 2560-9.
[http://dx.doi.org/10.2337/dc18-1749] [PMID: 30287422]
[163]
Anselmino M, Öhrvik J, Malmberg K, Standl E, Rydén L. Glucose lowering treatment in patients with coronary artery disease is prognostically important not only in established but also in newly detected diabetes mellitus: a report from the Euro Heart Survey on Diabetes and the Heart. Eur Heart J 2008; 29(2): 177-84.
[http://dx.doi.org/10.1093/eurheartj/ehm519] [PMID: 18156611]
[164]
Smooke S, Horwich TB, Fonarow GC. Insulin-treated diabetes is associated with a marked increase in mortality in patients with advanced heart failure. Am Heart J 2005; 149(1): 168-74.
[http://dx.doi.org/10.1016/j.ahj.2004.07.005] [PMID: 15660049]
[165]
Herman ME, O’Keefe JH, Bell DSH, Schwartz SS. Insulin Therapy Increases Cardiovascular Risk in Type 2 Diabetes. Prog Cardiovasc Dis 2017; 60(3): 422-34.
[http://dx.doi.org/10.1016/j.pcad.2017.09.001] [PMID: 28958751]
[166]
Price HI, Agnew MD, Gamble J-M. Comparative cardiovascular morbidity and mortality in patients taking different insulin regimens for type 2 diabetes: a systematic review. BMJ Open 2015; 5(3): e006341.
[http://dx.doi.org/10.1136/bmjopen-2014-006341] [PMID: 25762229]

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