Cardiovascular Benefit of Glucagon‐Like Peptide‐1 Receptor Agonists in Female Patients With Type 2 Diabetes Mellitus: A Meta‐Analysis of Recent Cardiovascular Outcome Trials


BACKGROUND: Several studies have confirmed a higher diabetes-associated relative risk of cardiovascular (CV) disease in women compared to men. Recent CV outcome trials have demonstrated CV benefit of glucagon-like peptide 1 (GLP-1) receptor agonists in patients with type 2 diabetes mellitus (T2DM). However, most trials were underpowered to make definitive conclusions for women.

METHODS: We performed a meta-analysis of randomized CV outcome trials published after the issuance of Food and Drug Administration Guidance on antihyperglycemic medications in 2008.

RESULTS: Five CV outcome trials assessing the CV benefit of GLP-1 receptor agonists in T2DM were identified (LEADER, SUSTAIN-6, EXSCEL, HARMONY, and ELIXA). The ELIXA trial was excluded given the different primary outcome and the lack of gender outcome data. The four trials included in this meta-analysis enrolled 36,852 individuals, and 13,129 were female (36%). The composite primary outcome of CV death, non-fatal MI, or non-fatal stroke occurred in 537 of the 6,513 females (8.2%) treated with a GLP-1 receptor agonists compared to 643 of 6,616 females (9.7%) treated with placebo (Hazard Ratio 0.83, 95% CI 0.74-0.94) (figure). The test for heterogeneity was not significant (p=0.39).

CONCLUSIONS: Women are underrepresented in clinical trials assessing the effect of GLP-1 receptor agonists on CV outcomes in T2DM. The results of this meta-analysis confirm a CV benefit of GLP-1 receptor agonists in women with diabetes and high CV risk.

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Aguilar D, Koutroumpakis E, Taegtmeyer H. J Am Coll Cardiol 2019;73(Suppl 1):239.