GLPwatch
Risk of major adverse cardiovascular events and all-cause mortality under treatment with GLP-1 RAs or the dual GIP/GLP-1 receptor agonist tirzepatide in overweight or obese adults without diabetes: a systematic review and meta-analysis.
Ther Adv Neurol Disord · 2024
Last updated 2026-05-28A review of 16 clinical trials involving 28,168 overweight or obese adults without diabetes found that GLP-1 drugs (like liraglutide and semaglutide) and tirzepatide reduced the risk of major heart problems by 21% and all-cause death by 20% compared to a placebo. These drugs also lowered the risk of heart attacks by 28%, but their effects on stroke risk were unclear due to limited data.
AI summary of the abstract below.
| Journal | Ther Adv Neurol Disord, 2024 |
|---|---|
| Citations | 22 |
| Relative citation ratio | 4.09 |
| NIH percentile | 90 |
| Molecules | tirzepatide |
| Conditions studied | Obesity, Cardiovascular Risk Reduction |
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.
Verbatim abstract via PubMed 39345822 ↗
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