Why it matters: Zealand and Roche are betting that petrelintide’s tolerability can distinguish it in the crowded obesity market. The latest results strengthen that argument, but raise questions about its competitiveness as a standalone treatment for people who also have type 2 diabetes.
Zoom in: The 220-participant ZUPREME-2 trial met its primary endpoint, with all three petrelintide doses producing statistically significant weight loss versus placebo after 28 weeks.
- Average weight loss reached up to 9.2%, versus 2% with placebo.
- Gastrointestinal side effects caused 1.9% of petrelintide recipients to discontinue treatment, versus 1.7% on placebo.
Yes, but: Patients with obesity and type 2 diabetes need treatments that address both weight and blood sugar. Petrelintide lowered HbA1c, a measure of average blood sugar levels over roughly three months, by up to 0.65 percentage points at 28 weeks. It’s still progress compared to the 0.23-point rise observed with the placebo group, but far from being competitive.
- Novo Nordisk’s semaglutide 2.4 mg, for example, delivered a 1.6-point reduction at 68 weeks in STEP 2, while its experimental CagriSema combination achieved a 1.91-point reduction at 68 weeks in REIMAGINE 2.
The upside: Tolerability remains the strongest argument for Petrelintide. The drug mimics amylin, a hormone involved in feeling full, and Zealand reported that its tolerability was largely comparable to placebo.
- Gastrointestinal side effects caused 1.9% of petrelintide recipients to discontinue treatment, versus 1.7% on placebo. This advantage could matter as some people with overweight could benefit from a drug offering moderate weight reduction with fewer tolerability problems.
The big picture: Zealand has been here before. In March, petrelintide’s first Phase 2 readout delivered up to 10.7% weight loss at 42 weeks, but shares dropped more than 30% as investors sought stronger efficacy.
- Last week, Boehringer Ingelheim’s Zealand-originated survodutide delivered Phase 3 success in people with obesity and diabetes. However, gastrointestinal side effects caused 18% of treated participants to stop, and Zealand shares fell about 10% in early trading.
What’s next: Roche and Zealand have started three Phase 3 petrelintide trials expected to enroll about 7,000 participants. A Phase 2 combination study with Roche’s GLP-1/GIP drug enicepatide, formerly CT-388, is planned for the second half of 2026. That combination will test whether petrelintide can contribute to a stronger overall treatment profile.
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