# 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

## TL;DR

A new drug called ecnoglutide significantly improved blood sugar control in people with type 2 diabetes compared to a placebo.

## Contribution

Ecnoglutide, a cAMP-biased GLP-1 analogue, is shown to be effective as a monotherapy for type 2 diabetes.

## Key findings

- Ecnoglutide reduced HbA1c levels by 1.96% (0.6 mg) and 2.43% (1.2 mg) compared to a 0.87% reduction with placebo.
- The drug was well-tolerated and represents a potential monotherapy option for T2DM.
- The trial was completed with 211 participants randomized across 32 medical centers in China.

## 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 (HbA1c) 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 HbA1c (≤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 HbA1c 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.

Here the authors report a phase 3 clinical trial showing that Ecnoglutide, designed as a cAMP-biased GLP-1R agonist, improved glycaemic control versus placebo in adults with type 2 diabetes inadequately controlled with diet and exercise alone or with a single oral hypoglycaemic agent.