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

🎖️ Top 10% JournalSep 30, 2024Therapeutic advances in neurological disorders

Risk of major heart problems and death in overweight or obese adults without diabetes treated with GLP-1 or dual GIP/GLP-1 receptor drugs

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Abstract

Analysis of 28,168 participants showed that GLP-1 and GIP/GLP-1 receptor agonists reduced major adverse cardiovascular events by 21% compared to placebo.

GLP-1 and GIP/GLP-1 receptor agonists are associated with a reduction in all-cause mortality by 20% compared to placebo.
There is a trend indicating a decrease in cardiovascular mortality, although it did not reach statistical significance.
These agents lower the odds of myocardial infarction by 28% and nonfatal myocardial infarction by 28%.
No significant associations were found between the treatments and fatal myocardial infarction, stroke, or nonfatal stroke.
Future research is needed to better understand the effects of these treatments on stroke risk.

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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. p I p I p I p I p I2 2 2 2 2

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.

Key numbers

0.79

Decrease in Risk

from 7 RCTs comparing GLP-1 or / vs. placebo.

0.80

Decrease in All-Cause Mortality

from 15 RCTs comparing GLP-1 or / vs. placebo.

0.72

Decrease in Myocardial Infarction Risk

from 15 RCTs comparing GLP-1 or / vs. placebo.

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Abstract

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