Evaluating the therapeutic benefits and safety of ecnoglutide for type 2 diabetes: evidence from a systematic review and meta-analysis

Type 2 diabetes mellitus (T2DM) is a growing global health challenge, necessitating effective therapies that improve glycemic control and promote weight loss. Ecnoglutide, a novel cAMP-biased GLP-1 (glucagon-like peptide-1) receptor agonist, has emerged as a promising therapeutic option. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted following PRISMA and AMSTAR-2 guidelines. Electronic databases were searched up to February 2026. Eligible studies included adult patients with T2DM comparing ecnoglutide with placebo or active comparators. Outcomes included glycemic parameters, anthropometric measures, metabolic indices, and safety. Data were pooled using a random-effects model, and certainty of evidence was assessed using GRADE. Three RCTs comprising 979 participants were included. Ecnoglutide significantly reduced HbA1c (MD -0.57%, 95% CI -0.86 to -0.29) and fasting plasma glucose (MD -1.11 mmol/L, 95% CI -1.58 to -0.65), with a higher proportion achieving target HbA1c (RR 1.57, 95% CI 1.37–1.80). Significant reductions in body weight (MD -1.83 kg) and waist circumference (MD -1.53 cm) were also observed. Improvements in insulin resistance and lipid parameters were noted. Exploratory subgroup analyses did not establish a clear dose response relationship, while short-term trials showed larger glycemic reductions compared with longer follow up. Adverse events were more frequent but not statistically significant, with no increase in serious adverse events. Ecnoglutide demonstrates significant efficacy in improving glycemic control and weight-related outcomes in T2DM, with a safety profile comparable to existing GLP-1 receptor agonists. However, larger and longer-term studies are needed to confirm its cardiovascular benefits and long-term safety.