The obesity drug landscape
Amycretin entered the most active area of drug development in a generation, alongside approved incretin drugs and a…
Where amycretin sits in a crowded field
Amycretin entered the most active area of drug development in a generation, alongside approved incretin drugs and a wave of investigational amylin-based agents. The question everyone asks is how it compares.
The answer has to start with a fact that is easy to skip: no randomised trial has compared amycretin with any other agent. Everything in this unit is either an indirect estimate or a statement about the shape of the evidence, and this unit is mostly about reading indirect estimates without being fooled by them.
Key terms
The only cross-agent estimate there is
There is no randomised comparison of amycretin against any other agent. The one quantitative cross-agent estimate is indirect: a network meta-analysis of amylin-based therapies that pooled six trials, 4642 participants in total, with follow-up ranging from 12 to 68 weeks. In its ranking, high-dose subcutaneous amycretin produced the largest reduction in percent body weight, a mean difference of -23.95% against placebo, ahead of high-dose eloralintide at -18.01% and high-dose CagriSema at -17.18%, all exceeding semaglutide 2.4 mg at -11.45%.
Three things are wrong with the obvious reading of that chart, and they compound. A mean difference is not a weight loss: it is the modelled gap against placebo, and where placebo gained weight the gap is larger than anything anyone lost. "High-dose subcutaneous amycretin" is a pooled stratum of two dose arms, not a dose, so no participant received a treatment with that result. And the whole thing is an indirect estimate, not a comparison. The near-match between -23.95% and the published -24.3% is a coincidence between two different quantities.
AdvancedWhy the comparison is tilted before it starts
The network used the longest available follow-up for each agent, a range of 12 to 68 weeks, so amycretin's arms are ranked against a semaglutide arm run for nearly twice as long. The estimands are mismatched too, and in the direction that flatters amycretin: the semaglutide trial reports a treatment-policy estimand, consistent with the intention-to-treat principle, which counts people who stopped treatment, while the amycretin inputs are hypothetical-estimand figures from a trial with a large unquantified number of withdrawals.