Reducing the risk of heart failure in diabetes mellitus: review of new therapeutics

Shreeharsh Godbole, Shreerang Godbole


Diabetes mellitus (DM) and heart failure (HF) are closely related: patients with diabetes have an increased risk of developing HF and those with HF are at higher risk of developing diabetes. When the two diseases are considered individually, HF has a much poorer prognosis than diabetes mellitus; therefore, treatment of HF is a priority in these group of patients. There are many drugs now available to achieve glycemic control in individuals with DM. However, as we enter an era of personalization in the management of DM, the next challenge will be the identification of therapeutic strategies that will not only achieve and maintain glycemic control, but that will also reverse existing complications. Given the high prevalence of HF in DM, there is a strong imperative to advance this field, with the view of identifying robust strategies that will not only improve long-term outcomes in subjects with DM and HF but also limit the likelihood of developing HF in the first place. Newer therapies like sodium- glucose transport protein- 2 inhibitors (SGLT-2 I) and sacubitril or valsartan have shown potential benefit for reducing the risk of heart failure in diabetic population. This review will summarize the new therapeutics to reduce the risk of HF in patients with DM.


Diabetes mellitus, Heart failure, Metformin, SGLT-2 inhibitors

Full Text:



International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: 2019. Available at:

Rosano GM, Vitale C, Seferovic P. Heart failure in patients with diabetes mellitus. Cardiac failure review. 2017;3(1):52.

Bell DS, Goncalves E. Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose‐lowering medications. Diabetes Obesity Metabol. 2019;21(6):1277-90.

Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979;241(19):2035-8.

Gilbert RE, Krum H. Heart failure in diabetes: effects of antihyperglycaemic drug therapy. Lancet. 2015;385(9982):2107-17.

David S. H. Bell MB, Edison Goncalves MD. Heart failure in the patient with diabetes: Epidemiology, aetiology, prognosis, therapy and the effect of glucose lowering medications. Diabetes Obes Metab. 2019;21(6):1277-90.

Gu J, Pan JA, Fan YQ, Zhang HL, Zhang JF, Wang CQ. Prognostic impact of HbA1c variability on long-term outcomes in patients with heart failure and type 2 diabetes mellitus. Cardiovascular Diabetol. 2018;17(1):96.

Yokota S, Tanaka H, Mochizuki Y, Soga F, Yamashita K, Tanaka Y, et al. Association of glycemic variability with left ventricular diastolic function in type 2 Diabetes Mellitus. Journal of the American College of Cardiology. 2019;73(9):764.

Stratton IM, Adler AI, Neil HA, Manley SE, Holman RR, Turner RC, 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.

Control G, Turnbull FM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52(11):2288-98.

Group AS, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575-85

ADVANCE Collaborative Group, 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.

Rosengren A, Vestberg D, Svensson AM, Kosiborod M4, Clements M5, Rawshani A, et al. Long-term excess risk of heart failure in people with type 1 diabetes: a prospective case control study. Lancet Diabetes Endocrinol. 2015;3(11):876-85

Wong AK, AlZadjali MA, Choy AM, Lang CC. Insulin resistance: a potential new target for therapy in patients with heart failure. Cardiovasc Ther. 2008;26(3):203-13.

Papanas N, Maltezos E, Mikhailidis DP. Metformin and heart failure: never say never again, Expert Opinion on Pharmacotherapy. 2012;13:1-8.

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. Circulation: Heart Failure. 2013;6(3):395-402.

Cosentino F. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. European Heart J. 2019;41(2):255-323.

Kenny HC, Abel ED. Heart failure in type 2 diabetes mellitus: impact of glucose-lowering agents, heart failure therapies, and novel therapeutic strategies. Circulation Res. 2019;124(1):121-41.

Pafili K, Papanas N. Sodium-glucose cotransporter-2 inhibitors in type 2 diabetes: a magic potion to reduce heart failure? Expert Rev Clin Pharmacol. 2019;12(8):693-5.

Verma S, Lam CS, Kosiborod M. Empagliflozin and Heart Failure: What Can We Learn From EMPRISE? Circulation. 2019;139:2831-4

Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362:772-6.

Moye LA, Pfeffer MA, Wun CC, Davis BR, Geltman E, Hayes D, et al. Uniformity of captopril benefit in the SAVE Study: subgroup analysis. Survival and Ventricular Enlargement Study. Eur Heart J 1994;15:2-8.

Ryden L, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Packer M, et al. Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur Heart J 2000;21:1967-78.

Kenny HC, Abel ED. Heart failure in type 2 diabetes mellitus: impact of glucose-lowering agents, heart failure therapies, and novel therapeutic strategies. Circulation Res. 2019;124(1):121-41.

Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709-17.

Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11-21.

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004.

Yandrapalli S, Andries G, Biswas M, Khera S. Profile of sacubitril/valsartan in the treatment of heart failure: patient selection and perspectives. Vascular Health Risk Management. 2017;13:369.

Bobbio M, Ferrua S, Opasich C, Porcu M, Lucci D, Scherillo M, et al. Survival and hospitalization in heart failure patients with or without diabetes treated with beta-blockers. J Card Fail. 2003;9:192-202.

Deedwania PC, Giles TD, Klibaner M, Ghali JK, Herlitz J, Hildebrandt P, et al. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF. Am Heart J. 2005;149:159-67.

Reil JC, Tardif JC, Ford I, Lloyd SM, O’Meara E, Komajda M, et al. Selective heart rate reduction with ivabradine unloads the left ventricle in heart failure patients. J Am Coll Cardiol. 2013;62:1977-85.

Komajda M, Tavazzi L, Francq BG, Bohm M, Borer JS, Ford I, et al. Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial. Eur J Heart Fail 2015;17:1294-301.

Rogers JK, Jhund PS, Perez AC, Böhm M, Cleland JG, Gullestad L, et al. Effect of rosuvastatin on repeat heart failure hospitalizations: the CORONA Trial (Controlled Rosuvastatin Multinational Trial in Heart Failure). JACC Heart Fail. 2014;2:289-97.