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Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis

M. Bethel, R. Patel, P. Merrill, Y. Lokhnygina, J. Buse, R. Mentz, N. Pagidipati, J. Chan et al.

The Lancet Diabetes and Endocrinology, 2017

513 citations

Abstract

BACKGROUND

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide.

METHODS

In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) for cardiovascular efficacy outcomes and odds ratios for key safety outcomes.

FINDINGS

Of 12 articles identified in our search and screened for eligibility, four trials of cardiovascular outcomes of GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide). Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary…

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