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Meta-Analysis
. 2021 Sep 22;31(10):2745-2755.
doi: 10.1016/j.numecd.2021.06.002. Epub 2021 Jul 5.

Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials

Edoardo Mannucci  1 , Besmir Nreu  1 , Chiara Montereggi  1 , Benedetta Ragghianti  1 , Marco Gallo  2 , Andrea Giaccari  3 , Matteo Monami  4 ; SID-AMD joint panel for Italian Guidelines on Treatment of Type 2 Diabetes
Collaborators, Affiliations
Free article
Meta-Analysis

Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials

Edoardo Mannucci et al. Nutr Metab Cardiovasc Dis. .
Free article

Abstract

Aims: Meta-analyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on major cardiovascular events (MACE), mortality, and heart failure. Aim of this meta-analysis of randomized trials is the assessment of the cardiovascular safety of DPP4i.

Data synthesis: A Medline, Embase, Cochrane database search for sitagliptin, vildagliptin, omarigliptin, saxagliptin, alogliptin, trelagliptin, anagliptin, linagliptin, gemigliptin, evogliptin, and teneligliptin was performed up to up January 1st, 2020. All trials with a duration ≥24 weeks and comparing the effects of DPP4i with placebo or active drugs were collected. Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. A total of 182 eligible trials were identified. DPP-4i were not associated with an increased risk of MACE (MH-OR 0.99 [0.93, 1.04]), all-cause mortality (MH-OR 0.99 [0.93, 1.06]), and heart failure (MH-OR 1.05 [0.96, 1.15]) with no significant differences across individual molecules, except for saxagliptin, which was associated with an increased risk of heart failure.

Conclusions: As a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure.

Keywords: DPP-4 inhibitors; Major cardiovascular adverse events; Meta-analysis.

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Conflict of interest statement

Declaration of competing interest BN is presently an employee of Novo Nordisk; CM, MG, and AG have no conflicts of interest to declare; MM has received speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Bristol Myers Squibb; EM has received consultancy fees from Merck and Novartis, speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis, and research grants from Merck, Novartis, and Takeda. All the authors approved the final version of this manuscript. Dr. Matteo Monami is the person who takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

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