AI Article Synopsis
- GLP-1 receptor agonists (liraglutide, semaglutide, tirzepatide) may lower cardiovascular risk in overweight/obese individuals without diabetes.
- A systematic review of 16 trials involving over 28,000 participants showed these medications reduced major adverse cardiovascular events and all-cause mortality compared to placebo.
- While they significantly lowered the risk of myocardial infarction, the relationship with stroke is less clear due to limited data.
Article Abstract
Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes.
Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population.
Data Sources And Methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke.
Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71-0.89; < 0.01; = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70-0.92; < 0.01; = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71-1.01; = 0.06; = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61-0.86; < 0.01; = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61-0.85; < 0.01; = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered.
Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents.
Trial Registration: PROSPERO CRD42024515966.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437580 | PMC |
| http://dx.doi.org/10.1177/17562864241281903 | DOI Listing |
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