Skip to main content

Advertisement

SpringerLink
Log in

Prevention of Heart Failure in Patients with Diabetes: Role of Diabetes Medications

  • Diabetes and Cardiovascular Disease (ND Wong, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Type 2 diabetes mellitus (DM) is a major risk factor for the development of heart failure (HF). In patients with DM, preventing HF using diabetes medications should be an imperative for primary care physicians and cardiologists alike.

Recent Findings

Prior studies with DPP-IV inhibitors, thiazolidinediones (TZDs), and GLP-1 agonists have demonstrated either a neutral effect on HF or increased HF hospitalizations. Two recent large-scale randomized controlled trials (RCTs), EMPA-REG OUTCOME and CANVAS, compared sodium glucose transporter-2 inhibitor (SGLT-2i) to placebo. Use of SGLT-2i led to a substantial reduction in HF events and hospitalizations in patients with DM, with or without history of HF.

Summary

Use of SGLT-2i therapy has been shown to reduce HF in patients with DM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. CDC National Diabetes Statistics Report, 2017: Estimates of Diabetes and its Burden in the United States. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf

  2. Moss SE, Klein R, Klein BE. Cause-specific mortality in a population-based study of diabetes. Am J Public Health. 1991;81:1158–62.

    Article  CAS  Google Scholar 

  3. McMurray JJV, Gerstein HC, Holman RR, Pfeffer MA. Heart failure: a cardiovascular outcome in diabetes that can no longer be ignored. Lancet Diabetes Endocrinol. 2014;2:843–51.

    Article  CAS  Google Scholar 

  4. Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham study. JAMA. 1979;241:2035–8.

    Article  CAS  Google Scholar 

  5. Nichols GA, Gullion CM, Koro CE, et al. The incidence of congestive heart failure in type 2 diabetes. Diabetes Care. 2004;27(8):1879–84.

    Article  Google Scholar 

  6. Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation. 2001;103:2668–73.

    Article  CAS  Google Scholar 

  7. Bertoni AG, Hundley WG, Massing MW, et al. Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care. 2004;27(3):699–703.

    Article  Google Scholar 

  8. Gustafsson I, Brendorp B, Seibaek M, et al. Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure. JACC. 2004;43:771–7.

    Article  Google Scholar 

  9. Carr AA, Kowey PR, Devereux RB, et al. Hospitalizations for new heart failure among subjects with diabetes mellitus in the RENAAL and LIFE studies. Am J Cardiol. 2005;96:1530–6.

    Article  Google Scholar 

  10. American Diabetes Association. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S86–S104. https://doi.org/10.2337/dc18-S009.

    Article  Google Scholar 

  11. The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369:145–54.

    Article  Google Scholar 

  12. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Eng J Med. 2003;348:383–93.

    Article  Google Scholar 

  13. Oellgaard J, Gaede 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 randomized Steno-2 study. Diabetologia. 2018;61:1724–33.

    Article  CAS  Google Scholar 

  14. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703–13.

    Article  Google Scholar 

  15. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published online November 13, 2017]. Hypertension. https://doi.org/10.1161/HYP.0000000000000065.

  16. HOPE Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in patients with diabetes mellitus: results of the HOPE study and Micro-HOPE substudy. Lancet. 2000;355:253–9.

    Article  Google Scholar 

  17. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines. Circulation. 2014;129:S1–45.

    Article  Google Scholar 

  18. Preiss D, Campbell RT, Murray HM, et al. The effect of statin therapy on heart failure events: collaborative meta-analysis of unpublished data from major randomized trials. Eur Heart J. 2015;36:1536–46.

    Article  CAS  Google Scholar 

  19. Turnbull FM, Abraira C, Anderson RJ, et al. Intesive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52:2288–98.

    Article  CAS  Google Scholar 

  20. Turner, R for the UKPDS group. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–65.

    Article  Google Scholar 

  21. Boussageon R, Supper I, Bejan-Angoulvant T, et al. Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. PLoS Med. 2012;9(4):e1001204.

    Article  Google Scholar 

  22. Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009;339:b4731.

    Article  Google Scholar 

  23. 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;352:837–53.

    Article  Google Scholar 

  24. Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Eng J Med. 2008;358:2560–72.

    Article  CAS  Google Scholar 

  25. Gerstein HC, Miller ME, Byington RP, et al. Effect of intensive glucose lowering in type 2 diabetes. N Eng J Med. 2008;358:2545–59.

    Article  CAS  Google Scholar 

  26. Dormandy JA, Charbonnel B, Eckland DJA, 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 randomized controlled trial. Lancet. 2005;366:1279–89.

    Article  CAS  Google Scholar 

  27. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomized, open label trial. Lancet. 2009;373:2125–35.

    Article  CAS  Google Scholar 

  28. Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319–28.

    Article  CAS  Google Scholar 

  29. Gerstein HC, Jung H, Ryden L, et al. Effect of Basal Insulin Glargine on First and Recurrent Episodes of Heart Failure Hospitalization: the ORIGIN trial. Circulation. 2018;137:88–90.

    Article  CAS  Google Scholar 

  30. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–26.

    Article  CAS  Google Scholar 

  31. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Eng J Med. 2013;369:1327–35.

    Article  CAS  Google Scholar 

  32. Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking aloglipitin versus placebo in EXAMINE: a multicentre, randomized, double-blind trial. Lancet. 2015;385:2067–76.

    Article  CAS  Google Scholar 

  33. Green JB, Bethel A, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232–42.

    Article  CAS  Google Scholar 

  34. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247–57.

    Article  CAS  Google Scholar 

  35. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Eng J Med. 2016;375:311–22.

    Article  CAS  Google Scholar 

  36. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375:1834–44.

    Article  CAS  Google Scholar 

  37. Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377:1228–39.

    Article  CAS  Google Scholar 

  38. Abdul-Ghani MA, Norton L, DeFranzo RA. Efficacy and safety of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus. Curr Diab Rep. 2012;12:230–8.

    Article  CAS  Google Scholar 

  39. Heise T, Seewaldt-Becker E, Macha S, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab. 2013;15:613–21.

    Article  CAS  Google Scholar 

  40. Lytvyn Y, Bjornstad P, Udell JA, et al. SGLT2 Inhibitors in Heart Failure: potential mechanisms, clinical applications, and summary of clinical trials. Circulation. 2017;136:1643–58.

    Article  CAS  Google Scholar 

  41. Baker WL, Smyth LR, Riche DM, et al. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8:262–75.e9.

    Article  CAS  Google Scholar 

  42. •• Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117–28. https://doi.org/10.1056/NEJMoa1504720. The first randomized trial of an antidiabetic agent (the SGLT-2i empagliflozin) to demonstrate a meaningful reduction in HF

    Article  CAS  Google Scholar 

  43. Kaul S. Mitigating Cardiovascular Risk in Type 2 Diabetes With Antidiabetes Drugs: A Review of Principal Cardiovascular Outcome Results of EMPA-REG OUTCOME, LEADER, and SUSTAIN-6 Trials. Diabetes Care. 2017;40(7):821–31.

    Article  CAS  Google Scholar 

  44. Jessup M. Neprilysin inhibition – a novel therapy for heart failure. N Engl J Med. 2014;371:1062–4.

    Article  Google Scholar 

  45. • Neal B, Perkovic V, Mahaffey K, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377:644–57. Landmark trial showing reduction in HF with use of SGLT-2i canagliflozin

    Article  CAS  Google Scholar 

  46. • Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. 2018;319(15):1580–91. A comprehensive meta-analysis of antidiabetic medications, showing superiority of SGLT-2i on HF outcomes

    Article  CAS  Google Scholar 

  47. Kosiborod M, Cavender MA, Fu AZ. 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. Circulation. 2017;136:249–59.

    Article  CAS  Google Scholar 

  48. Birkeland KI, Jorgensen ME, Carstensen B, et al. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. Lancet Diabetes Endocrinol. 2017;5(9):709–17.

    Article  CAS  Google Scholar 

  49. Kosiborod M, Lam CSP, Kohsaka S, on behalf of the CVD-REAL Investigators and Study Group, et al. Lower Cardiovascular Risk Associated with SGLT-2i in >400,000 Patients: The CVD-REAL 2 Study. JACC. 2018; https://doi.org/10.1016/j.jacc.2018.03.009.

    Article  CAS  Google Scholar 

  50. Cooper HA, Dries DL, Davis CE, et al. Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. Circulation. 1999;100:1311–5.

    Article  CAS  Google Scholar 

  51. Packer M, Anker SD, Butler J, et al. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure. JAMA Cardiology. 2017;2(9):1025–9.

    Article  Google Scholar 

  52. Lytvyn Y, Bjornstad P, Udell JA. Sodium glucose cotransporter-2 inhibition in heart failure: potential mechanisms, clinical applications, and summary of clinical trials. Circulation. 2017;136:1643–58.

    Article  CAS  Google Scholar 

  53. Wiviott SD, Raz I, Bonaca MP, et al. The design and rationale for the dapagliflozin effect on cardiovascular events (DECLARE)-TIMI 58 trial. Am Heart J. 2018;200:83–9.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UCLA Division of Cardiology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Nikhil Bassi & Gregg C. Fonarow

  2. Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan-UCLA Medical Center, 10833 LeConte Ave, Room 47–123 CHS, Los Angeles, CA, 90095-1679, USA

    Gregg C. Fonarow

Authors
  1. Nikhil Bassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gregg C. Fonarow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregg C. Fonarow.

Ethics declarations

Conflict of Interest

Nikhil Bassi reports no relevant disclosures.

Gregg C. Fonarow reports significant consulting for Novartis, and modest consulting for Amgen, Bayer, Gambro, Medtronic, St. Jude, and Janssen, and research funding from the NIH. Dr. Fonarow holds the Eliot Corday Chair of Cardiovascular Medicine at UCLA and is also supported by the Ahmanson Foundation (Los Angeles, California).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Diabetes and Cardiovascular Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bassi, N., Fonarow, G.C. Prevention of Heart Failure in Patients with Diabetes: Role of Diabetes Medications. Curr Cardiol Rep 20, 112 (2018). https://doi.org/10.1007/s11886-018-1050-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-018-1050-3

Keywords

Search

Navigation