What Is Petrelintide?

1. How does petrelintide work?

Amylin is a hormone the pancreas secretes with insulin after eating. It slows gastric emptying, suppresses glucagon, and produces satiety through its own receptors in the brainstem, a pathway separate from the GLP-1 and GIP receptors that semaglutide and tirzepatide act on. Native amylin lasts minutes; pramlintide, the approved analogue, lasts hours and needs an injection at every meal. Petrelintide is engineered for once-weekly dosing.

The pharmacological argument for amylin is tolerability. Amylin agonists produce satiety with less of the nausea and vomiting that limit GLP-1 dose escalation, so the expected trade is smaller weight loss alone but a better partner for an incretin drug. That is the design of Novo Nordisk’s CagriSema, and it is Roche’s plan for petrelintide.

2. How much weight do people lose on petrelintide?

ZUPREME-1, NCT06662539, randomised 493 adults with obesity or overweight and no diabetes to placebo or one of five dose levels of petrelintide, escalated every fourth week, across a 2-to-3-week screening period, 42 weeks of treatment, and a nine-week safety follow-up (participants were tracked for anti-drug antibodies through week 51). The primary endpoint, percent change in body weight from baseline to week 28, was met in all five dose arms against placebo, and Roche describes the result as statistically significant and clinically meaningful; the company has not published the week-28 percentage itself, only that the week-42 result was sustained from it. Secondary endpoints tracked the share of participants losing at least 5% and at least 10% of body weight at weeks 28 and 42, absolute weight change, waist circumference, and metabolic markers including HbA1c, fasting glucose, hsCRP, and lipids at week 42; none of those figures have been released either.

Neither Roche nor the ClinicalTrials.gov record discloses the milligram dose at each of the five arms; the registry lists them only as Dose 1 through Dose 5 against matching placebo. For comparison, in separate and longer trials semaglutide 2.4 mg produced 14.9% at 68 weeks and tirzepatide 15 mg 20.9% at 72 weeks; Lilly’s amylin agonist eloralintide produced 20.1% at 48 weeks on its top dose. Petrelintide’s number is the lowest of the three. ZUPREME-2, NCT06926842, tested three doses (again undisclosed in mg) against matching placebo in six arms, in 221 adults with type 2 diabetes and obesity or overweight; it started dosing in April 2025, used the same week-28 percent-weight-change primary endpoint, added hypoglycemic episodes to its safety tracking given the diabetic population, and completed in August 2026. Results have not been published.

Before ZUPREME-1, two Phase 1 trials set up the dose-escalation design: a single-ascending-dose study from 0.04 mg to 2.4 mg subcutaneous (plus a 0.35 mg intravenous arm), and a multiple-ascending-dose study from 0.6 mg to 9.0 mg once weekly, published in Diabetes, Obesity and Metabolism in 2026. In the 16-week arm of that Phase 1b trial, weight loss reached up to 8.6%, and nausea occurred in 16.7% to 33.3% of petrelintide recipients versus 16.7% on placebo; only one participant vomited and discontinued for it. Zealand designed the ZUPREME-1 escalation schedule specifically to bring nausea down from those Phase 1b rates, and Roche’s release says it worked: nausea in ZUPREME-1 was less common than in the Phase 1b trial, and almost no nausea was reported once participants reached their maintenance dose.

3. What are the side effects of petrelintide?

Gastrointestinal, mild, and at rates close to placebo. Roche’s release reports that the most common adverse events were gastrointestinal, the vast majority mild; vomiting in the most effective arm was zero, and across all petrelintide arms combined it was lower than on placebo; diarrhea and constipation rates were consistent with placebo and stayed in single digits; and no unexpected safety signals were observed. The adverse-event discontinuation figure, 4.8% against 4.9% on placebo, is the number Roche leads with, and it is the reason the drug is being built into a combination rather than positioned against tirzepatide. That tolerability is a step up from the Phase 1b trial that preceded ZUPREME-1, where nausea affected 16.7% to 33.3% of recipients (see below); Zealand redesigned the dose-escalation schedule for ZUPREME-1 specifically to fix that.

4. What is the Roche deal and the combination plan?

On March 12, 2025 Roche licensed petrelintide from Zealand Pharma for $1.65 billion upfront, up to $1.2 billion in development milestones tied mainly to Phase 3 starts, and up to $2.4 billion in sales milestones, a total of up to $5.3 billion. Profits and losses are shared 50/50 in the U.S. and Europe; elsewhere Roche holds exclusive rights and pays Zealand royalties.

The reason Roche paid that much is enicepatide, formerly CT-388 and now carrying the Roche compound code RO7795068, its own GLP-1/GIP dual agonist. The stated plan is a fixed-dose combination of petrelintide and enicepatide, the same architecture as CagriSema: an incretin drug for the bulk of the weight loss, an amylin drug to add to it without adding nausea. That combination is registered as NCT07589686, a Roche-sponsored Phase 2, randomized, double-blind, placebo-controlled, dose-finding trial of petrelintide co-administered with RO7795068 in 486 adults with obesity or overweight, across six arms comparing the combination with each monotherapy and placebo; it was not yet recruiting as of the registry’s most recent update, with an estimated start of September 2026. Phase 3 trials of petrelintide alone for chronic weight management were planned for the second half of 2026; Zealand and Roche have not disclosed a program name or planned enrollment size.

In their April 2026 joint statement, the companies described ZUPREME-1 as showing “double-digit weight loss with placebo-like tolerability” and called petrelintide “a highly tolerable alternative that promotes long-term adherence.” Those are the sponsors’ characterizations, not an independent finding, and Roche’s own release attributes the tolerability framing to CMO Levi Garraway, who said petrelintide “achieved meaningful weight loss with a well-tolerated dosing approach.”

5. How does petrelintide compare with the other amylin drugs?

The eloralintide and cagrilintide pages cover the other two. Petrelintide’s combination with enicepatide is registered as a Phase 2 trial, NCT07589686; eloralintide’s combination with tirzepatide is also in Phase 2, and cagrilintide’s combination as CagriSema is in Phase 3.

For a log, an investigational drug is entered like any other: product, date, milligrams, and site. How GLP-1 tracking works covers what to record.

6. Petrelintide FAQ

• How much weight do people lose on petrelintide?

  In ZUPREME-1, up to 10.7% mean weight loss at 42 weeks at the most effective dose, against 1.7% on placebo, in 493 adults with obesity or overweight and no diabetes. That is below the 15% to 21% seen with semaglutide and tirzepatide at their top doses, in separate and longer trials.

• What are the side effects of petrelintide?

  Mainly mild gastrointestinal effects. In ZUPREME-1, 4.8% of the most-effective-dose arm stopped for adverse events versus 4.9% on placebo; that arm had no cases of vomiting, and diarrhea and constipation stayed in single digits. Overall discontinuation for any reason was 8.4% on petrelintide versus 13.6% on placebo.

• How is petrelintide different from a GLP-1 drug?

  Different hormone. Amylin is released with insulin and signals fullness through its own receptors. GLP-1 drugs act on the incretin receptors. Amylin drugs tend to produce less weight loss alone, which is why every company developing one plans to combine it with an incretin drug.

• What is the Roche deal?

  In March 2025 Roche licensed petrelintide from Zealand Pharma for $1.65 billion upfront, with up to $1.2 billion in development milestones and $2.4 billion in sales milestones, a total of up to $5.3 billion. The companies share profits and losses 50/50 in the U.S. and Europe. Roche's own GLP-1/GIP agonist, enicepatide (CT-388), is the planned combination partner.

• Is petrelintide approved?

  No. Phase 2 is complete in people without diabetes (ZUPREME-1) and with type 2 diabetes (ZUPREME-2, results not yet public). Zealand and Roche said Phase 3 trials for weight management would start in the second half of 2026. No filing exists.

• What did the earlier Phase 1 trials show?

  Two placebo-controlled Phase 1 trials preceded ZUPREME-1: a single-ascending-dose study (0.04 mg to 2.4 mg subcutaneous, plus a 0.35 mg intravenous arm) and a multiple-ascending-dose study (0.6 mg to 9.0 mg once weekly), published in Diabetes, Obesity and Metabolism in 2026. Over 16 weeks, weight loss reached up to 8.6%, and nausea occurred in 16.7% to 33.3% of petrelintide recipients versus 16.7% on placebo. Zealand redesigned the dose-escalation schedule for ZUPREME-1 to reduce that nausea rate.

• Is petrelintide being tested with enicepatide?

  Yes. NCT07589686 is a Roche-sponsored Phase 2 trial combining petrelintide with enicepatide (Roche code RO7795068, formerly CT-388) in 486 adults with obesity or overweight, comparing the combination against each monotherapy and placebo. It was not yet recruiting as of the registry's latest update, with an estimated September 2026 start.

7. Sources