Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials.

Purpose: This study aimed to investigate the effects of randomized, placebo-controlled trials involving the GLP-1 and glucagon receptor dual agonists, mazdutide, and cotadutide, on glycaemic control and body weight changes in individuals with type 2 diabetes mellitus (T2DM), obesity, or both.

Methods: We conducted searches in Medline, PubMed, Scopus, the Cochrane database, and Web of Science up to March 5, 2024. The primary outcomes assessed were changes in HbA1c level and percentage changes in body weight from baseline (CFB).

Results: Eleven studies and four unpublished trials were included. The pooled meta-analysis revealed a significant reduction in HbA1c (MD = -0.63%; 95% CI = [-0.82, -0.44]; P < 0.00001), fasting plasma glucose (MD = -1.71 mmol/L; 95% CI = [-2.31, -1.10]; P < 0.00001), and percentage change in body weight (MD = -4.16%; 95% CI = [-5.41, -2.92]; P < 0.00001). Safety analysis revealed no significant change in serious adverse events (OR = 1.03; 95% CI = [0.61, 1.75]; P = 0.91), but there were significantly higher odds of treatment-emergent adverse events (OR = 2.52; 95% CI = [1.92, 3.30]; P < 0.00001) and vomiting (OR = 6.05; 95% CI = [3.52, 10.40]; P < 0.00001).

Conclusion: These results suggest that mazdutide and cotadutide are effective for glycaemic control and weight reduction in individuals with T2DM, obesity, or both.