Current Cardiology Reports

, 21:100 | Cite as

Strategies for Appropriate Selection of SGLT2-i vs. GLP1-RA in Persons with Diabetes and Cardiovascular Disease

  • Devinder S. Dhindsa
  • Anurag Mehta
  • Pratik B. Sandesara
  • Aneesha Thobani
  • Stephen Brandt
  • Laurence S. SperlingEmail author
Diabetes and Cardiovascular Disease (N Wong, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Diabetes and Cardiovascular Disease


Purpose of Review

This review will serve to highlight the clinical rationale used in the selection of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) or glucagon-like peptide 1 receptor agonists (GLP1-ra).

Recent Findings

SGLT2-i and GLP1-ra are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit in multiple cardiovascular outcomes trials (CVOTs), with benefits that are consistent across class of medication.


Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) and glucagon-like peptide 1 receptor agonists (GLP1-ra) are the first anti-hyperglycemics to demonstrate significant cardiovascular benefit. Given the unique side effect and benefit profiles, appropriate consideration of these agents with a focus on cardiovascular risk reduction requires an individualized approach.


Diabetes Cardiovascular disease Sodium-glucose cotransporter 2 inhibitor Glucagon-like peptide 1 receptor agonist Prevention 


Compliance with Ethical Standards

Conflict of Interest

Devinder S. Dhindsa, Anurag Mehta, Pratik B. Sandesara, Aneesha Thobani, Stephen Brandt, and Laurence S. Sperling declare that they have no conflicts of interest.

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.


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

  1. 1.
    Cubbon RM, Wheatcroft SB, Grant PJ, Gale CP, Barth JH, Sapsford RJ, et al. Temporal trends in mortality of patients with diabetes mellitus suffering acute myocardial infarction: a comparison of over 3000 patients between 1995 and 2003. Eur Heart J. 2007;28(5):540–5.CrossRefGoogle Scholar
  2. 2.
    Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group Lancet (London, England) 1998;352(9131):837–53.Google Scholar
  3. 3.
    Effects of intensive glucose lowering in type 2 diabetes. 2008;358(24):2545–59.Google Scholar
  4. 4.
    Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. 2008;358(24):2560–72.Google Scholar
  5. 5.
    •• Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28 This study was the first cardiovascular outcomes trial to show a benefit of an anti-hyperglycemic medication in cardiovascular outcomes. Empagliflozin demonstrated a large and surprising benefit in cardiovascular endpoints as compared with placebo. CrossRefGoogle Scholar
  6. 6.
    Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. 2017;377(7):644–57.Google Scholar
  7. 7.
    Fitchett D, investigators tE-ROt, Zinman B, investigators tE-ROt, Wanner C, investigators tE-ROt, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J. 2016;37(19):1526–34.CrossRefGoogle Scholar
  8. 8.
    Rådholm K, Figtree G, Perkovic V, Solomon Scott D, Mahaffey Kenneth W, de Zeeuw D, et al. Canagliflozin and heart failure in type 2 diabetes mellitus. Circulation. 2018;138(5):458–68.CrossRefGoogle Scholar
  9. 9.
    • Kato Eri T, Silverman Michael G, Mosenzon O, Zelniker Thomas A, Cahn A, Furtado Remo HM, et al. Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus. Circulation. 2019;139:2528–36. This study showed that the benefit of the SGLT2 inhibitors is particularly evident in heart failure with reduced ejection fraction. CrossRefGoogle Scholar
  10. 10.
    Neeland IJ, McGuire DK, Chilton R, Crowe S, Lund SS, Woerle HJ, et al. Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus. Diab Vasc Dis Res. 2016;13(2):119–26.CrossRefGoogle Scholar
  11. 11.
    Tikkanen I, Narko K, Zeller C, Green A, Salsali A, Broedl UC, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38(3):420–8.CrossRefGoogle Scholar
  12. 12.
    Dhindsa DS, Sandesara PB, Shapiro MD. The intersection of diabetes and cardiovascular disease—a focus on new therapies. Frontiers in Cardiovascular Medicine. 2018;5:160.Google Scholar
  13. 13.
    Mudaliar S, Alloju S, Henry RR. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME study? A unifying hypothesis. Diabetes Care. 2016;39(7):1115–22.CrossRefGoogle Scholar
  14. 14.
    Rosenstock J, Jelaska A, Frappin G, Salsali A, Kim G, Woerle HJ, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37(7):1815–23.CrossRefGoogle Scholar
  15. 15.
    Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380:2295–306.CrossRefGoogle Scholar
  16. 16.
    Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129(5):587–97.CrossRefGoogle Scholar
  17. 17.
    Kosiborod M, Cavender Matthew A, Fu Alex Z, Wilding John P, Khunti K, Holl Reinhard W, et al. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs. Circulation. 2017;136(3):249–59.CrossRefGoogle Scholar
  18. 18.
    Mehta A, Marso SP, Neeland IJ. Liraglutide for weight management: a critical review of the evidence. Obes Sci Pract. 2017;3(1):3–14.CrossRefGoogle Scholar
  19. 19.
    • 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 This study was the first to show cardiovascular benefit among the GLP1 receptor agonists, showing a reduction in cardiovascular mortality in those randomized to liraglutide as compared with placebo. CrossRefGoogle Scholar
  20. 20.
    Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44.CrossRefGoogle Scholar
  21. 21.
    Hernandez AF, Green JB, Janmohamed S, D’Agostino RB, Granger CB, Jones NP, 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.CrossRefGoogle Scholar
  22. 22.
    Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014;15(3):181–7.CrossRefGoogle Scholar
  23. 23.
    •• Das SR, Everett BM, Birtcher KK, Brown JM, Cefalu WT, Januzzi JL, et al. 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease. A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2018;72(24):3200–23. Major statement by the American College of Cardiology urging the consideration and use of SGLT-2 inhibitors and GLP-1 receptor agonists among cardiologists. Google Scholar
  24. 24.
    Tanaka A, Node K. Increased amputation risk with canagliflozin treatment: behind the large cardiovascular benefit? Cardiovasc Diabetol. 2017;16(1):129.CrossRefGoogle Scholar
  25. 25.
    Trujillo JM, Nuffer WA. Impact of sodium-glucose cotransporter 2 inhibitors on nonglycemic outcomes in patients with type 2 diabetes. Pharmacotherapy. 2017;37(4):481–91.CrossRefGoogle Scholar
  26. 26.
    Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015;38(9):1638–42.CrossRefGoogle Scholar
  27. 27.
    Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care. 2011;34(Suppl 2):S279–84.CrossRefGoogle Scholar
  28. 28.
    Storgaard H, Cold F, Gluud LL, Vilsboll T, Knop FK. Glucagon-like peptide-1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes. Diabetes Obes Metab. 2017;19(6):906–8.CrossRefGoogle Scholar
  29. 29.
    Bjerre Knudsen L, Madsen LW, Andersen S, Almholt K, de Boer AS, Drucker DJ, et al. Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology. 2010;151(4):1473–86.CrossRefGoogle Scholar
  30. 30.
    Vilsboll T, Bain SC, Leiter LA, Lingvay I, Matthews D, Simo R, et al. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab. 2018;20(4):889–97.CrossRefGoogle Scholar
  31. 31.
    Frías JP, Guja C, Hardy E, Ahmed A, Dong F, Öhman P, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4(12):1004–16.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Devinder S. Dhindsa
    • 1
  • Anurag Mehta
    • 1
  • Pratik B. Sandesara
    • 1
  • Aneesha Thobani
    • 2
  • Stephen Brandt
    • 3
  • Laurence S. Sperling
    • 1
    Email author
  1. 1.Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Department of MedicineEmory University School of MedicineAtlantaUSA
  2. 2.Department of Internal MedicineEmory University School of MedicineAtlantaUSA
  3. 3.Division of Endocrinology, Department of MedicineEmory University School of MedicineAtlantaUSA

Personalised recommendations