The short answer
Adding experimental PYY1875 to semaglutide produced extra weight reduction, but digestive side effects made treatment harder to tolerate.
What was tested?
After 32 weeks taking semaglutide, 83 adults with obesity entered a 16-week add-on study. Everyone continued weekly semaglutide 2.4 mg. They received PYY1875 at one of two doses or placebo; the 1 mg dose was evaluated for weight-loss efficacy.
Percentage points versus placebo; all continued semaglutide 2.4 mg weekly
PYY1875 1 mg add-on
2.2 percentage points more loss
Original visual based on the study.
| Group or measure | Result |
|---|---|
| PYY1875 1 mg add-on | 2.2 percentage points more loss |
The benefit was modest
The adjusted additional weight reduction with 1 mg PYY1875 was 2.2 percentage points compared with placebo. That difference refers to the add-on period—not total loss since starting semaglutide. The authors did not consider the benefit clinically meaningful.
Tolerability mattered
Digestive adverse events occurred in about 68% versus 29% of participants receiving the 1 mg add-on versus placebo. Only 20 of the 47 participants assigned that add-on were taking the target dose at the end.
The lesson
More ingredients or hormone targets do not automatically make a better treatment. A useful new option needs a meaningful benefit that people can tolerate. This small, short study cannot settle what other combinations might achieve.
Novo Nordisk sponsored the study.