Hormonal
Adding the long-acting PYY3-36 analogue PYY1875 (1.0 mg/week) to semaglutide (2.4 mg/week) yields only modest, non-clinically meaningful additional weight loss in people with obesity and is poorly tolerated due to gastrointestinal adverse events.
For individuals already on semaglutide, adding PYY1875 at 1.0 mg weekly provides only a small, likely unnoticeable additional weight loss benefit while significantly increasing the risk of gastrointestinal side effects like nausea. The 2.0 mg dose was not tolerated. Current evidence suggests this combination is not a viable strategy for improving weight loss outcomes due to poor tolerability and lack of clinical significance.
In the phase 2 study, a modest but not clinically meaningful treatment effect of PYY1875 1.0 mg versus placebo as an add-on to semaglutide 2.4 mg was observed. However, gastrointestinal-related adverse events were common with the 1.0-mg PYY1875 dose, and the 2.0-mg PYY1875 dose escalation regimen was not tolerated (both as add-ons to semaglutide).
Why this rating
Based on randomized, double-blind, placebo-controlled Phase 2 clinical trials (Part 2a and 2b) with robust safety monitoring.
Source
Long‐acting <scp>PYY<sub>3</sub></scp><sub>−36</sub> analogue with semaglutide for obesity: from preclinical assessment through randomized clinical studies
Birgitte S. Wulff et al. · Obesity · 2025
DOI 10.1002/oby.24329
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