Petrelintide
An amylin analog as an alternative to GLP-1 receptor agonists for weight management
Petrelintidea (formerly ZP8396) is an investigational long-acting amylin analog for once-weekly subcutaneous administration.
Amylin is produced in the pancreatic beta cells and co-secreted with insulin in response to ingested nutrients. Amylin analogs have been shown to increase satiety (feeling of fullness) by a direct effect on the amylin receptor and by restoring sensitivity to the hormone leptin. This is in contrast to GLP-1 receptor agonists that primarily lower body weight by reducing appetite.
Current clinical and preclinical data suggest a potential for long-acting amylin analogs to deliver a reduction in body weight that is comparable to GLP-1 receptor agonists but with improved tolerability for a better patient experience and a potential for the preservation of lean muscle.
Petrelintide has been designed with chemical and physical stability and no fibrillation around neutral pH, allowing for co-formulation and co-administration with other peptides.
aZealand Pharma has a collaboration and license agreement with Roche for petrelintide, including co-development and co-commercialization in the U.S. and Europe.
- PROGRAM Petrelintide
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PARTNERS
- Phase 3
Development status
Petrelintide will advance into Phase 3 clinical trials for chronic weight management, with a planned initiation in the second half of 2026.
The Phase 2 clinical program comprised two trials in people living with overweight or obesity. ZUPREME-1 enrolled people with obesity or overweight without type 2 diabetes, with 42 weeks of treatment, and completed enrollment in March 2025. ZUPREME-2 is for people with obesity or overweight with type 2 diabetes over 28 weeks of treatment and was initiated in April 2025. 42-week topline results from the ZUPREME-1 trial were reported in the first half of 2026, and topline results for the ZUPREME-2 trial are expected in the second half of 2026.
We have previously evaluated petrelintide in a Phase 1b multiple ascending dose (MAD) clinical trial.
In Part 1 of this Phase 1b MAD trial, low doses of 0.6 mg and 1.2 mg petrelintide administered weekly over six weeks showed an average weight loss of 5.3% and 5.1%, respectively. Petrelintide was well-tolerated with no serious or severe treatment-emergent adverse events and no withdrawals from the trial. All gastrointestinal adverse events reported were mild. These results were reported in 2023.
Part 2 of the Phase 1b MAD trial explored significantly higher doses of petrelintide over a longer duration of 16 weeks. In the trial, petrelintide demonstrated mean body weight reductions of 4.8%, 8.6% and 8.3% after 16 once-weekly doses of up to 2.4 mg, 4.8 mg and 9.0 mg, respectively, versus 1.7% for the pooled placebo group. Dose escalation within cohorts occurred every second week. Participants randomized to petrelintide received the three different maintenance doses of 2.4 mg, 4.8 mg and 9.0 mg for twelve, eight and six weeks, respectively. 79% of the 48 trial participants were male and mean BMI was 29.9. Petrelintide was assessed to be well tolerated in the trial, with no serious or severe adverse events. All gastrointestinal adverse events were mild, except for two moderate events (nausea and vomiting) reported in one participant who discontinued treatment. No other participants discontinued treatment due to adverse events. No other events of vomiting occurred, and two events of diarrhea were reported, both of which were mild. These results were presented at the Obesity Society Annual Meeting (ObesityWeek) in 2024.
Petrelintide is an investigational compound whose safety and efficacy have not been evaluated or approved for marketing by any regulatory authority.
A global collaboration & license agreement
In March 2025, Zealand Pharma and Roche entered a global collaboration and license agreement to co-develop and co-commercialize petrelintide and combination products with petrelintide, including a fixed-dose combination product of petrelintide and CT-388, Roche’s lead incretin asset and potential best-in-class GLP-1/GIP receptor dual agonist. This collaboration reflects our shared vision to develop petrelintide as a future foundational therapy for weight management and related comorbidities, redefining the standard of care for people with overweight and obesity by establishing the leading amylin-based franchise.
Related scientific publications
All scientific publications-
Effects of the novel long-acting amylin analog petrelintide on body weight and waist circumference by sex in a Phase 1 trial
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Safety, Tolerability, and Clinical Effects of Petrelintide (ZP8396), A Long-acting Amylin Analog
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Petrelintide (ZP8396) selectively reduces intake of high fat diet in DIO rats
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Petrelintide (ZP8396) significantly reduces fat mass while preserving lean mass in DIO rats
Learn about clinical trials involving petrelintide
Obesity
More about the disease area
Overweight and obesity are associated with more than 220 complications and comorbidities, including cardiovascular disease, liver disease, type 2 diabetes, kidney disease, and neuroinflammation.
