Efficacy of GLP-1 Receptor Agonist-Based Therapies on Cardiovascular Events and Cardiometabolic Parameters in Obese Individuals Without Diabetes: A Meta-Analysis of Randomized Controlled Trials.
Yin. Yue Y; Zhang. Minghan M; Cao. Qiuyu Q; Lin. Lin L; Lu. Jieli J; Bi. Yufang Y; Chen. Yuhong Y
Key Findings
- GLP‑1RA therapies lowered total cardiovascular events by about 19% and major adverse events by 20% versus placebo.
- Tirzepatide produced the biggest drop in BMI (‑6.5 kg/m²) and modest HbA1c reduction, while orfroglipron cut systolic blood pressure by ~7 mmHg.
- Retatrutide (and semaglutide) gave the strongest improvements in lipid profiles and reduced C‑reactive protein, a marker of inflammation.
Practical Outcomes
- For biohackers, adding a GLP‑1RA like tirzepatide or retatrutide can be a powerful tool to lower heart‑risk and shed weight without needing diabetes. Monitor blood pressure, lipids and CRP to gauge benefits, and consider dose titration protocols used in the trials (starting low, gradual increase) to minimize side effects. These findings support using GLP‑1RAs as part of a longevity‑focused regimen.
Summary
A big review of 29 trials found that drugs that act like GLP‑1 (including the newer peptide retatrutide) cut heart‑related events and improve blood pressure, weight, cholesterol and inflammation in overweight people who don’t have diabetes. This means you can get heart‑health and weight‑loss benefits from these drugs even if you’re not diabetic.
Abstract
The cardioprotective effects of glucagon-like peptide-1 receptor agonist (GLP-1RA)-based therapies in nondiabetic individuals with overweight or obesity remain underexplored. This meta-analysis evaluates their impact on cardiovascular events and metabolic parameters in this population. A meta-analysis was conducted using PubMed, Embase, Cochrane, and Web of Science databases from inception to June 18, 2024. Eligible studies were randomized controlled trials (RCTs) enrolling nondiabetic adults with overweight or obesity. These studies compared GLP-1RA-based therapies with placebo and reported cardiovascular events and metabolic parameters. A total of 29 RCTs involving 9 GLP-1RA-based drugs and 37 348 eligible participants were included. Compared to placebo, GLP-1RA-based therapies significantly reduced the risk of total cardiovascular events (relative risk: 0.81, 95% confidence interval [CI]: [0.76, 0.87]), major adverse cardiovascular events (0.80, [0.72, 0.89]), myocardial infarction (0.72, [0.61, 0.85]), and all-cause mortality (0.81, [0.71, 0.93]). No significant differences were observed in cardiovascular death or stroke. Additionally, GLP-1RA-based therapies were associated with significant reductions in some cardiometabolic parameters. Among GLP-1RA-based therapies, orfroglipron demonstrated strong benefits in reducing systolic blood pressure (mean difference: -7.10 mmHg, 95% CI: [-11.00, -2.70]). Tirzepatide induced the greatest reduction in body mass index (-6.50 kg/m<sup>2</sup>, [-7.90, -5.10]) and hemoglobin A1c concentrations (-0.39%, [-0.52, -0.26]). Retatrutide and semaglutide were most effective in improving lipid profiles and reducing C-reactive protein levels (-1.20 mg/dL, [-1.80, -0.63]), respectively. In nondiabetic individuals with overweight or obesity, GLP-1RA-based therapies significantly reduce cardiovascular events and improve cardiometabolic parameters. These findings underscore the potential for individualized GLP-1RA-based therapies targeting cardiovascular risk factors.
Study Information
pubmed
2025
2025-04-01T00:00:00.000Z
10.1111/1753-0407.70082
6
63