Dose-response and time-course effects of ecnoglutide in type 2 diabetes: a systematic review and meta-analysis of efficacy.

BACKGROUND

Ecnoglutide, a novel long-acting GLP-1 receptor agonist, is considered a promising therapeutic option for the treatment of diabetes. This study aims to evaluate the efficacy and safety of ecnoglutide in adults with type 2 diabetes and to further investigate its dose-time relationship.

METHODS

This study followed the PRISMA guidelines and systematically searched PubMed, Web of Science, Embase, and Cochrane Library, with the search updated through February 2026. Randomized controlled trials comparing ecnoglutide with placebo or the active control, dulaglutide, were included. The primary outcome was the change in HbA1c (%). Secondary outcomes included FPG, PPG, 7-point SMBG, body weight, adverse events, and serious adverse events. Risk of bias was assessed using the Cochrane RoB-2 tool. Meta-analyses employed a random-effects model, and mean differences and risk ratios were calculated with 95% confidence intervals.

RESULTS

Three randomized controlled trials involving 977 participants were included. Compared with placebo, ecnoglutide significantly reduced HbA1c (MD = -1.40, 95% CI -1.65, -1.14, p < 0.00001), FPG (MD = -1.98, 95% CI -2.34, -1.63, p < 0.00001), PPG (MD = -4.88, 95% CI -6.32, -3.44, p < 0.00001), and body weight (MD = -2.16, 95% CI -2.62, -1.71, p < 0.00001). Additionally, compared with the placebo group, the incidence of adverse events was higher in the ecnoglutide group (OR = 2.03, 95% CI 1.24-3.32, p = 0.005), while there was no significant difference in the incidence of serious adverse events. Dose-response analysis showed that ecnoglutide exhibited a clear dose-dependent relationship for HbA1c, FPG, and body weight at doses ranging from 0.4 to 1.2 mg, while PPG was less affected by dose. Time-response analysis indicated that the hypoglycemic efficacy of ecnoglutide peaked around week 35 and subsequently plateaued, whereas body weight exhibited a sustained linear downward trend.

CONCLUSION

Ecnoglutide significantly improved glycemic control and reduced body weight, although it was associated with a higher incidence of adverse events without increasing serious adverse events. Despite these promising findings, the evidence remains limited and requires confirmation in larger, multicenter randomized controlled trials.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261327235, identifier CRD420261327235.