Ecnoglutide is a once-weekly GLP-1 receptor agonist engineered to favor one signaling pathway, and it is not approved or sold outside China. In its phase 3 trial, weight fell 13.2% at week 40 on the 2.4 mg dose against 0.1% on placebo [1]. It appeared first as one of the thinly evidenced agents in a network meta-analysis of drugs for overweight and obesity[2]. This site reads that analysis in the network meta-analysis of nineteen drugs. It now has a completed trial behind it.
It is described as a cAMP-biased GLP-1 receptor agonist. The engineering favors one downstream signaling pathway over another, with the intention of separating the metabolic effects from the gastrointestinal ones. Whether that worked is the interesting question, and the trial provides a partial answer.
On weight it performed well. Across 664 randomized adults at 36 Chinese centers, week-40 weight loss was 9.1%, 10.9% and 13.2% at the three doses against 0.1% on placebo. The top dose gave a treatment difference of -13.3% (97% CI -15.3 to -11.3). Eighty-seven percent of that group lost at least 5% of their body weight, against 16% on placebo.
On tolerability the picture is less distinctive than the design promised. Treatment-emergent adverse events occurred in 93% of each ecnoglutide group against 84% on placebo, most commonly mild to moderate gastrointestinal events, and ten participants stopped because of them. That is broadly the profile of the existing drugs rather than an escape from it. Tolerability is what drives most discontinuation in this class, as titration and nausea describes.
The trial was funded by Hangzhou Sciwind Biosciences, which makes the drug. That is ordinary for a phase 3 trial and worth stating rather than implying. Almost every pivotal obesity trial is sponsor-funded, including the ones behind the drugs people take today. The thing to weigh is the follow-up rather than the funding. Forty weeks says nothing about year three, which is where the questions in what these drugs do to muscle and the measured lunch actually live.