Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a multi-centre, randomised, double-blind, placebo-controlled, phase 3 trial

Abstract Ecnoglutide is a cAMP-biased GLP-1 analogue developed for the treatment of type 2 diabetes mellitus (T2DM) and obesity. We conducted a randomised, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy and safety of ecnoglutide in adults with T2DM inadequately controlled with diet and exercise alone or with a single oral hypoglycaemic agent. The primary endpoint was change in glycated haemoglobin (HbA 1c ) from baseline at week 24. Between 29 December 2022 and 12 June 2024, 211 participants from 32 medical centres in China were randomised (2:2:1:1) to receive double-blind, once-weekly ecnoglutide (0.6 mg [n = 69] or 1.2 mg [n = 71]) or volume-matched placebo (0.6 mg [n = 36] or 1.2 mg [n = 35]) for 24 weeks. The randomisation, stratified by baseline HbA 1c (≤8.5% or >8.5%), was conducted via an interactive web response system. Ecnoglutide and placebo were identical in appearance to achieve masking. The trial was completed. All randomised participants received ≥1 dose of the assigned treatment and thus were included for analyses. At week 24, the least squares mean changes from baseline in HbA 1c were −1.96% (95% CI −2.18 to −1.73) with ecnoglutide 0.6 mg and −2.43% (95% CI −2.65 to −2.20) with ecnoglutide 1.2 mg versus −0.87% (−1.09 to −0.65) with placebo. The estimated treatment differences versus placebo were −1.09% (95% CI −1.40 to −0.77; p = 0.0003) with ecnoglutide 0.6 mg and −1.56% (95% CI −1.87 to −1.24; p < 0.0001) with ecnoglutide 1.2 mg. Ecnoglutide represents a potential monotherapy option for T2DM. This trial was registered at clinicaltrials.gov with the registration number NCT05680155.