Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis

Feb 24, 2024European stroke journal

Risk of serious heart problems and stroke linked to diabetes treatment with GLP-1 or dual GIP/GLP-1 receptor drugs

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Abstract

In a meta-analysis of 13 randomized controlled trials involving 65,878 patients with type 2 diabetes (T2DM), GLP-1 receptor agonists significantly reduced major adverse cardiovascular events (MACE).

GLP-1 receptor agonists or GIP/GLP-1 receptor agonists reduced MACE by 13% compared to placebo.
All-cause mortality decreased by 12% with GLP-1 receptor agonists.
Cardiovascular mortality was also reduced by 12% in patients treated with GLP-1 receptor agonists.
The odds of stroke were lowered by 16%, while nonfatal stroke risk decreased by 15%.
GLP-1 receptor agonists significantly prevented ischemic stroke, but did not show an association with fatal stroke.

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INTRODUCTION: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM.

PATIENTS AND METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo).

RESULTS: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; < 0.01; = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; < 0.01; = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; < 0.01; = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; < 0.01; = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; < 0.01; = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; = 0.105; = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; < 0.01; = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; = 0.792; = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction. p I p I p I p I p I p I p I p I2 2 2 2 2 2 2 2

DISCUSSION AND CONCLUSION: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.

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Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis

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