Ecnoglutide serves up weight-loss benefit for nondiabetic adults with overweight, obesity

Treatment with the novel cyclic adenosine monophosphate (cAMP)-biased GLP-1 receptor agonist ecnoglutide for weight management is safe and results in substantial and sustained weight loss in adults with obesity or overweight but without diabetes, according to a phase III study.

Conducted at 36 medical centres across China, the study included 664 nondiabetic adults with BMI ≥28 kg/m² or ≥24 kg/m² plus at least one weight-related comorbidity (eg, prediabetes, hypertension, hyperlipidaemia, metabolic dysfunction-associated steatotic liver disease, obstructive sleep apnoea syndrome, or weight-bearing joint pain).

The participants were randomly assigned to receive ecnoglutide at 1.2 (n=166), 1.8 (n=166), or 2.4 mg (n=167) or volume-matched placebo (n=165). The coprimary endpoints of percentage change in bodyweight and proportion of participants with a reduction of at least 5 percent in bodyweight at week 40 were evaluated in the full analysis population, which included all randomly assigned participants who were exposed to at least one dose of study drug or placebo according to their assigned treatment group. Safety was also assessed in all participants who received at least one dose and had a safety assessment after medication.

At week 40, ecnoglutide yielded significant reductions in bodyweight compared with placebo, with the respective estimated treatment differences being –9.2 percent (97 percent confidence interval [CI], –11.0 to –7.5) with the 1.2-mg dose, –11.1 percent (97 percent CI, –13.1 to –9.1) with the 1.8-mg dose, and –13.3 percent (–15.3 to –11.3) with the 2.4-mg dose (p<0.0001 for all).

Likewise, the number of participants who achieved at least a 5-percent reduction in bodyweight at week 40 was significantly greater with ecnoglutide vs placebo (77 percent with 1.2 mg, 84 percent with 1.8 mg, and 87 percent with 2.4 mg vs 16 percent with placebo; p<0.0001 for all).

Treatment-emergent adverse events (AEs) occurred in 93 percent of participants in the ecnoglutide 1.2-mg group, 93 percent in the 1.8-mg group, 93 percent in the 2.4-mg group, and 84 percent in the placebo group. Mild-to-moderate gastrointestinal related events were the most common. AEs led to treatment discontinuation in 10 participants in the combined ecnoglutide groups.