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Could we soon have the final evidence of cardiovascular safety of DPP-4 inhibitors?


Authors: Žák P.
Authors‘ workplace: II. interní klinika LF MU a FN U sv. Anny v Brně
Published in: Kardiol Rev Int Med 2019, 21(1): 33-36

Overview

Heart failure is a common complication in patients with DM2, and is associated with poor long-term prognosis. Understanding the potential adverse effects of antidiabetic drugs is critical. The SAVOR-TIMI 53 trial with DPP-4 inhibitor saxagliptin in patients at high cardiovascular risk showed an increased risk of heart failure (HF) requiring hospitalization. Approximately 50% of patients with DM2 have proven diabetic kidney disease, which is associated with a significant increase of the risk of progression to end-stage kidney disease and an increased risk of premature death. The CARMELINA study with DPP-4 inhibitor linagliptin proved non-inferiority for the primary outcome (the time to the first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke). CARMELINA was also designed to evaluate renal outcomes of linagliptin treatment; there was no significant difference between linagliptin and placebo for composite renal outcome. In June this year we should receive the results of a further study with CV objectives, CAROLINA, where linagliptin treatment is compared with the active component sulphonylurea (glimepiride). We should soon receive a full image of cardiovascular safety of treatment with DPP-4 inhibitors.

Keywords:

heart failure – cardiovascular risk – kidney disease – DPP-4 inhibitors


Sources

1. 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): 2457–2471. doi: 10.1056/NEJMoa072761.

2. Center for Drug Evaluation and Research, Food and Drug Administration. Diabetes mellitus – evaluating cardiovascular risk in new antidiabetic ther­apies to treat type 2 diabetes. Guidance for industry. Silver Spring 2008. Available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071627.pdf.

3. Committee for Medicinal Products for Human Use (CHMP). Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus. London: European Medicines Agency 2012. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guide­line/2012/06/WC500129256.pdf.

4. Smith RJ, Goldfine AB, Hiatt WR. Evaluating the cardiovascular safety of new medications for type 2diabetes: time to reassess? Diabetes Care 2016; 39(5): 738–742. doi: 10.2337/dc15-2237.

5. Thomas MC, Cooper T, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol 2016; 12(2): 73–81. doi: 10.1038/nrneph.2015.173.

6. Gansevoort RT, Correa-Rotter R, Hemmelgarn BRet al. Chronic kidney disease and cardio-vascular risk: epidemiology, mechanisms, and prevention. Lancet 2013; 382(9889): 339–352. doi: 10.1016/S0140-6736(13)60595-4.

7. Cooper ME, Perkovic V, McGill JB et al. Kidney dis­ease end points in a pooled analysis of individual patient‑level data from a large clinical trials program of the dipeptidyl peptidase 4 inhibitor linagliptin in type 2 diabetes. Am J Kidney Dis 2015; 66(3): 441–449. doi: 10.1053/j.ajkd.2015.03.024.

8. Rosenstock J, Perkovic V, Alexander JH et al. CARMELINA® investigators. Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk. Cardiovasc Diabetol 2018; 17(1): 39. doi: 10.1186/s12933-018-0682-3.

9. Scirica BM, Braunwald E, Raz I et al. SAVOR-TIMI 53 Steering Committee and Investigators. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation 2014; 130(18): 1579–1588. doi: 10.1161/CIRCULATIONAHA.114.010389.

10. Zannad F, Cannon CP, Cushman WC et al. EXAMINE Investigators. 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): 2067–2076. doi: 10.1016/S0140-6736(14)62225-X.

11. Green JB, Bethel MA, Armstrong PW et al. TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 373(3): 232–242. doi: 10.1056/NEJMoa1501352.

12. Karásek D. EMPA-REG OUTCOME a snížení rizika srdečního selhání u nemocných s diabetem. Interní Med 2016; 18(4): 163–167.

13. Introduction: Standards of Medical Care in Diabetes – 2018. Diabetes Care 2018; 41 (Suppl 1): S1–S2. doi: 10.2337/dc18-Sint01.

14. Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and cardiovascular outcomes in type 2diabetes. N Engl J Med 2016; 375(4): 311–322. doi: 10.1056/NEJMoa1603827.

15. Marso SP, Bain SC, Consoli A et al. Semaglutide and cardio-vascular outcomes in patients with type 2diabetes. N Engl J Med 2016; 375(19): 1834–1844. doi: 10.1056/NEJMoa1607141.

16. 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): 644–657.

17. Ou HT, Chang KC, Li CY et al. Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: a nation-wide longitudinal study. Cardiovasc Diabetol 2016; 15

18. Kim YG, Yoon D, Park S et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in patients with type 2 diabetes mellitus: a population-based cohort study. Circ Heart Fail 2017; 10(9): e003957.

19. 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. doi: 10.1001/jama.2018.18269.

20. Cornel JH, Bakris GL, Stevens SR et al. TECOS Study Group. Effect of sitagliptin on kidney function and respective cardiovascular outcomes in type 2diabetes: outcomes from TECOS. Diabetes Care 2016; 39(12): 2304–2310. doi: 10.2337/dc16-1415.

21. Mosenzon O, Leibowitz G, Bhatt DL et al. Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial. Diabetes Care 2017; 40(1): 69–76. doi: 10.2337/dc16-0621.

22. Marx N, Rosenstock J, Kahn SE et al. Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin versus glimepiride in type 2diabetes (CAROLINA(R)). Diab Vasc Dis Res 2015; 12(3): 164–174. doi: 10.1177/1479164115570301.

Labels
Paediatric cardiology Internal medicine Cardiac surgery Cardiology
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