Cardiovascular outcomes during treatment with dipeptidyl peptidase-4 inhibitors depending on renal function and combination with metformin: a systematic review


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Background. Dipeptidyl peptidase-4 (DPP-4) inhibitors are generally an effective and safe class of antidiabetic drugs for the treatment of type 2 diabetes mellitus (DM2). To date, a series of large randomized controlled trials (RCTs) has been conducted on the cardiovascular safety of the use of DPP-4 inhibitors. Objective. Evaluation of the effect of DPP-4 inhibitors on the risk of cardiovascular events in subgroups of patients with different renal function, as well as among patients who received drugs of this class in addition to metformin. Methods. RCTs were searched in the National Institutes of Health PubMed database for key words as of 12/09/2021. Outcomes assessed included the MACE composite endpoint, death from cardiovascular causes, non-fatal acute myocardial infarction, and non-fatal stroke. Results. In DM2 patients with a high risk of MACE and preserved kidney function, therapy with DPP-4 inhibitor (alogliptin) was associated with a reduced risk ratio for the development of tripartite (RR=0.81; 95% CI: 0.65-0.99) and quadruple (RR=0, 82; 95% CI: 0.650.99) MACE and death from cardiovascular causes (RR=0.61; 95% CI: 0.41-0.92). The addition of alogliptin to metformin compared with metformin alone resulted in a reduced risk of MACE, as well as death from cardiovascular causes and death from all causes. In most studies, DPP-4 inhibitors did not affect the risks of cardiovascular outcomes. Conclusion. DPP-4 inhibitors did not increase the risk of developing cardiovascular events in DM2 patients, and some representatives may have a potential protective effect on the risks of developing certain cardiovascular events in patients with normal kidney function or early stages of chronic kidney disease (glomerular filtration rate> 60 ml/min/1.73 m2) and normoalbuminuria, as well as when used in combination with metformin.

Full Text

Restricted Access

About the authors

Nina A. Petunina

Sechenov University

Email: napetunina@mail.ru
Dr. Sci. (Med.), Professor, Corresponding Member of the RAS, Head of the Department of Endocrinology, Institute of Clinical Medicine Moscow, Russia

N. S Martirosyan

Sechenov University

Moscow, Russia

F. V Valeeva

Kazan State Medical University

Department of Hospital Therapy with a Course of Endocrinology Kazan, Russia

References

  1. Ma C.X., Ma X.N., Guan C.H., et al. Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management. Cardiovasc Diabetol 21, 74 (2022). doi: 10.1186/s12933-022-01516-6.
  2. Einarson T.R, Acs A., Ludwig C., Panton U.H. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17(1):83-3. doi: 10.1186/s12933-018-0728-6.
  3. Stratton I.M., Adler A.I., Neil H.A., et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ (Clinical research ed). 2000;321(7258):405-12 doi: 10.1136/bmj.321.72 58.405.
  4. Robins S.J., Rubins H.B., Faas F.H., et al. resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care. 2003;26(5):1513-17 doi: 10.2337/diacare.26.5.1513.
  5. Stephanie A., Amiel P.A., et al. Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol. 2019;7(5):385-96. doi: 10.1016/S2213-8587(18)30315-2.
  6. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein H.C., Miller M.E., Byington R.P, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-59. Doi: 10.1056/ NEJMoa0802743.
  7. Ferreira J., Mehta C., Sharma A., et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes: a renal function stratified analysis of the EXAMINE trial. BMC Med. 2020;18(1):165. doi: 10.1186/s12916-020-01616-8.
  8. Perkovic V., Toto R., Cooper M.E., et al. Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial. Diabetes Care. 2020;43(8):1803-12. Doi: 10.233 7/ dc20-0279.
  9. Udell J.A., Bhatt D.L., Braunwald E., et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment: observations from the SAVOR-TIMI 53 Trial. Diabetes Care. 2015;38(4):696-705. doi: 10.2337/dc14-1850.
  10. Green J.B., Bethel M.A., Armstrong P.W., et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015;373(3):232-42. doi: 10.1056/NEJMoa1501352.
  11. Cornel J.H., Bakris G.L., Stevens S.R., et al. Effect of Sitagliptin on Kidney Function and Respective Cardiovascular Outcomes in Type 2 Diabetes: Outcomes From TECOS. Diabetes Care. 2016;39(12):2304-10. Doi: 10.2337/ dc16-1415.
  12. Gallwitz B., Rosenstock J., Rauch T., et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380(9840):475-83. doi: 10.1016/S0140-6736(12)60691-6.
  13. White W.B., Heller S.R., Cannon C.P, et al. Alogliptin in Patients with Type 2 Diabetes Receiving Metformin and Sulfonylurea Therapies in the EXAMINE Trial. Am J Med. 2018;131(7):813-19e5. doi: 10.1016/j.amjmed.2018.02.023.
  14. Matthews D.R., Paldanius P.M., Proot P, et al. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial. Lancet. 2019;394(10208):1519-29. doi: 10.1016/S0140-6736(19)32131-2.
  15. Iqbal N., Parker A., Frederich R., Donovan M., Hirshberg B. Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials. Cardiovasc Diabetol. 2014;13:33. doi: 10.1186/1475-2840-13-33.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies