Comparative Efficacy and Safety of Ecnoglutide in Type 2 Diabetes: A Systematic Review and Meta‐Analysis

BACKGROUND: Type 2 diabetes mellitus (T2DM) affects over 500 million people worldwide, with traditional therapies often failing to maintain long-term glycaemic control. Ecnoglutide, a novel long-acting GLP-1 receptor agonist, has emerged as a promising therapeutic option. This systematic review and meta-analysis evaluated the efficacy and safety of ecnoglutide in adults with T2DM. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Cochrane Library, ScienceDirect, ClinicalTrials.gov, and Google Scholar through September 2025. Randomized controlled trials comparing ecnoglutide with placebo or active comparators in adults with T2DM were included. Primary outcomes were changes in HbA1c and body weight. Secondary outcomes included fasting plasma glucose, insulin resistance markers, lipid profile, liver enzymes, and adverse events. Risk of bias was assessed using the Cochrane RoB-2 tool. Meta-analysis was performed using random-effects models, with mean differences and risk ratios calculated at 95% confidence intervals. RESULTS: Four RCTs comprising 1643 participants (1162 receiving ecnoglutide, 444 controls) were included. Ecnoglutide significantly reduced HbA1c (MD = -0.44, 95% CI -0.55 to -0.33, p < 0.00001), body weight (MD = -5.63, 95% CI -7.90 to -3.35, p < 0.01), and fasting plasma glucose (MD = -0.81, 95% CI -1.03 to -0.59, p < 0.00001). Improvements were observed in insulin sensitivity, lipid profile, and liver enzymes. Adverse events occurred more frequently with ecnoglutide (RR = 1.09, p < 0.01), although predominantly gastrointestinal and mild-to-moderate, with no significant differences in serious adverse events. CONCLUSIONS: Ecnoglutide demonstrates robust efficacy in glycaemic control, weight reduction, and cardiometabolic parameters with an acceptable safety profile in adults with T2DM, supporting its therapeutic potential as a next-generation GLP-1 receptor agonist.