Could amylin meet the need of better tolerability for weight management medication?

While GLP1 weight management medications work well for many people, some struggle with gastrointestinal (GI) side effects. As we move forward in the obesity field, we are hard at work to develop medications that have less GI side effects.

As blogged previously, amylin is a hormone made by our pancreas, which is secreted when we eat. Amylin talks to our brain to tell us that we feel full, and is also believed to act on parts of the brain involved in the wanting and liking of food (the ‘hedonic’ area, see more on this here), thus having a potential impact on emotional eating and food preferences. It slows down the stomach in response to food intake, and also suppresses glucagon after meals. Petrelintide is one of several amylin analogs being explored as possible weight management medication.

A press release of topline results of a phase 2 study suggests that petrelintide can facilitate meaningful weight loss, with tolerability similar to placebo. This ZUPREME-1 study was a 42 week randomized controlled trial with 493 participants in USA, Poland and Romania, baseline BMI 37 kg/m2, evaluating five different doses of petrelintide compared to placebo. The found that weight loss was up to 10.7% vs 1.7% with placebo when treatment was taken as intended (scientists: the more conservative treatment regimen estimand was not released but stated to be ‘largely consistent’ with the above efficacy estimand). Females lost considerably more weight (how much has not yet been revealed) than men (as has been seen in trials of other obesity medications).

Similar proportions of people in petrelintide groups (4.8%) and placebo (4.9%) stopped treatment due to adverse events. The proportion of people experiencing vomiting was lower in all petrelintide groups compared to placebo; diarrhea and constipation were similar to placebo.

BOTTOM LINE: The amylin analog petrelintide facilitated meaningful weight loss (up to 10.7%), with placebo-like tolerability. I look forward to the full results publication to really dig into this – but these topline results indicate an exciting step forward in the pursuit of weight management medication that has better tolerability.

Disclaimer: I receive honoraria as a consultant from the makers of petrelintide (Roche).

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