The drugs on sale now are not the only ones coming, and the pipeline surveyed in the network meta-analysis of nineteen drugs included several agents with weak evidence behind them. One of those, ecnoglutide, now has a completed phase 3 trial [1].
It is described as a cAMP-biased GLP-1 receptor agonist, meaning it is engineered to favor 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, with the top dose giving 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, which matters given that the class's tolerability is what drives most discontinuation, 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 that established the drugs people take today. The thing to weigh is not the funding but the follow-up: 40 weeks says nothing about what happens in year three, which is where the questions in what these drugs do to muscle and the measured lunch actually live.