Effect of glucagon‐like peptide‐1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: A meta‐analysis of placebo‐controlled randomized trials

Abstract

Our aim was to study the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on the risk of any cardiovascular event in adults with overweight or obesity and without diabetes. We conducted a random-effects meta-analysis of placebocontrolled randomized controlled trials. Nine trials were eligible and, in total, 11 430 patients were included, of which 7702 (67%) were submitted to treatment with GLP-1 RA. During follow-up, 673 participants receiving GLP-1 RA treatment (8.7%) and 416 participants receiving placebo (11.2%) had a cardiovascular event. Treatment with GLP-1 RA versus placebo resulted in a reduction in the risk of any cardiovascular event (RR = 0.81, CI 0.70-0.92; p = .001). In overweight or obese adults without diabetes, treatment with GLP-1 RA reduced the risk of cardiovascular events. Our findings support the use of GLP-1 RA for reducing the cardiovascular risk of these patients.

Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial

“…Given the potential adverse effects of GLP‐1RAs in HFrEF, in patients with T2D or obesity with symptoms suggestive of or clinical suspicion of HF, an echocardiogram and natriuretic peptides may be considered before starting the treatment. On the other hand, in those without HFrEF, our results should not discourage clinicians from using GLP‐1RAs, given their well‐established atherosclerotic cardiovascular benefit in T2D 2 and their potential cardiovascular benefits in obesity 39 …”

“…On the other hand, in those without HFrEF, our results should not discourage clinicians from using GLP-1RAs, given their well-established atherosclerotic cardiovascular benefit in T2D 2 and their potential cardiovascular benefits in obesity. 39 Our study has some limitations. This was a post hoc analysis of an RCT and some studied endpoints did not reach the statistical significance threshold of 0.05; however, the consistent trend for increased risk of adverse events across different outcomes, the biological plausibility, and the finding of similar results in the LIVE trial provide robustness to our analyses.…”

“…On the other hand, in those without HFrEF, our results should not discourage clinicians from using GLP‐1RAs, given their well‐established atherosclerotic cardiovascular benefit in T2D 2 and their potential cardiovascular benefits in obesity. 39 …”

Methodological issues with meta‐analysis

“…Fortunately, we have the ongoing SELECT study 5 to answer the question of cardiovascular risk reduction with semaglutide in individuals with obesity and prior cardiovascular disease, but without diabetes. This study 5 is adequately powered (>17 500 participants), and the assessment of cardiovascular outcomes is much more stringent than in the Leite et al 1 meta-analysis. The study's duration is event-driven: there is adequate time allotted for determination of the primary outcome.…”

Letter of reply to the letter by Ryan

“…

We read with interest the comments of Professor Donna Ryan on our paper. 1,2 Professor Ryan raised some points in the letter, which we are most happy to clarify.

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