Effects of GLP-1 agonists on proportion of weight loss in obesity with or without diabetes: Systematic review and meta-analysis

To determine effects of glucagon-like peptide-1 (GLP-1) receptor agonists on ≥5% or ≥10% weight loss in overweight or obese patients with or without type 2 diabetes mellitus (T2DM). A systematic review and meta-analysis of placebo-controlled, randomized clinical trials (RCTs) ≥12 weeks’ duration. Registries were searched from inception to October 10, 2021. Sixty RCTs with 24,969 patients were included; 22 trials (median duration 39 weeks) with 17,183 patients (median age, 54.9 y; 64% female; median baseline weight, 96.2 kg) included data on ≥5% or ≥10% weight loss. Among GLP-1 receptor agonist-treated participants, 50.2% had ≥5% weight loss versus 17.1% placebo [odds ratio (OR), 5.03; 95% CI, 3.996.32]; 17.5% had ≥10% weight loss on agonists versus 3.1% placebo (OR, 5.31; 95% CI, 3.907.22). Highest proportion of ≥5% weight loss was achieved by semaglutide subcutaneous (SQ) 2.4 mg (OR 8.32, 95% CI 4.59–15.09), semaglutide SQ < 2.4 mg (OR 7.1, 95% CI 4.6–10.95), and liraglutide SQ > 1.8 mg (OR 4.28, 95% CI 3.37–5.43). Non-T2DM achieved significantly greater mean absolute weight loss than T2DM participants (coefficient: 2.47 kg, 95% CI: 4.12 to −0.82). Nausea was associated with greater mean absolute weight loss (coefficient: 0.12, 95% CI: 0.06–0.17). GLP-1 receptor agonists are efficacious in inducing ≥5% or ≥10% weight loss in T2DM and non-T2DM with overweight or obesity.