Quantitative Comparison of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Adults: A Systematic Review and Model-Based Meta-Analysis

🥈 Top 2% JournalFeb 6, 2025Diabetes technology & therapeutics

Comparing how diabetes drugs that activate GLP-1 receptors affect weight loss in adults

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

A total of 56,683 patients were analyzed to compare weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs).

Retatrutide (12 mg once weekly) resulted in a mean weight loss of -26.56%.
Tirzepatide (15 mg once weekly) showed weight loss of -22.76% in nondiabetic patients, -11.09% in Caucasian T2D patients, and -4.97% in Asian T2D patients.
Patients with higher baseline body weight may experience better weight loss outcomes.
Higher baseline glycated hemoglobin (HbA1c) is associated with improved blood sugar control.
Tirzepatide (10 mg once weekly) and oral orforglipron (10 mg daily) were the most effective drugs for glycemic control in T2D patients.

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The objective of this study is to quantitatively compare the weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adult patients with no diabetes and type 2 diabetes (T2D). PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase have been used as data sources from database inception to January 6, 2024. A total of 137 trials, encompassing 310 treatment arms, 17 GLP-1RAs, and 56,683 patients, were included in the analysis. The included trials were divided into three groups based on the characteristics of the populations: nondiabetic overweight or obesity group (NDOOG), type 2 diabetes Caucasian group (T2DCG), and type 2 diabetes Asian group (T2DAG). The effects of covariates were further evaluated, patients with a higher baseline body weight tend to have better weight loss outcomes, and patients with a higher baseline glycated hemoglobin (HbA1c) tend to achieve better blood sugar control. Five mathematical models were subjected to longitudinal analysis. In terms of Δ body weight, retatrutide (12 mg qw) was the most effective treatment (mean difference = -26.56% [95% confidence interval: -43.89% to -3.01%]). Tirzepatide (15 mg qw) demonstrated good weight loss ability in all three ΔBW models, ΔBW-NDOOG (-22.76% [-26.45% to -18.50%]), ΔBW-T2DCG (-11.09% [-12.39% to -9.44%])), and ΔBW-T2DAG (-4.97% [-5.84% to -4.12%]). In the aspect of ΔHbA1c, tirzepatide (10 mg qw) and oral orforglipron (10 mg qd) were the most effective drug, respectively. GLP-1RAs demonstrated effective weight management in both nondiabetic and T2D populations. Retatrutide achieved the most pronounced weight reduction, followed by tirzepatide. GLP-1RAs also significantly improved glycemic control for patients with T2D, with tirzepatide performing the best for glycemic control.

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