A huge new peptide called retatrutide (12 mg once a week) cut body weight by about 27% in clinical trials, beating all other GLP‑1 drugs. Tirzepatide also worked well, but not as dramatically. The study shows that people who start heavier lose more weight, and those with higher blood sugar see bigger glucose improvements.

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.