Petrelintide — What a New Weekly Amylin Drug Showed in Its Phase 2 Weight-Loss Trial

Bottom Line

In a 42-week, placebo-controlled Phase 2 trial of 485 adults, a once-weekly injection called petrelintide produced average weight loss of up to about 10% (up to 10.2% when everyone assigned to the drug is counted, up to 10.7% in people while they stayed on it), versus about 1.4% to 1.7% with placebo. It works through amylin, a different hormone pathway from GLP-1. Nausea was reported by about 20% of people on the drug versus 6% on placebo, and very few stopped for stomach reasons. It is not approved, it has not been tested head-to-head against Wegovy or Zepbound, so its roughly 10% result cannot be ranked against existing drugs. The interest is in what a different mechanism might add, especially for tolerability and in combination with GLP-1 drugs.

Background: What Is Amylin?

Amylin is a hormone made by the same pancreatic cells that make insulin. It slows the stomach’s emptying and acts on appetite centers in the brain to promote fullness, and it does so through receptors different from the GLP-1 receptor. Petrelintide is a long-acting amylin analog developed by Zealand Pharma in partnership with Roche. A related compound, cagrilintide, is already half of Novo Nordisk’s CagriSema, which we covered in our review of the REDEFINE trials. The question this trial begins to answer is whether an amylin drug can work as its own treatment, not just as a partner to a GLP-1.

That matters because stomach side effects are a common reason people have trouble staying on GLP-1 therapy, and the way people stop (and what happens afterward) is something we address directly in our guide to what happens after stopping Wegovy or Zepbound. A drug with a different mechanism and a gentler stomach profile is of obvious interest, which is why this paper drew attention at the 2026 European Association for the Study of Diabetes (EASD) meeting in Milan.

What the Trial Found

The ZUPREME-1 trial results were published online on September 29, 2026 in The Lancet Diabetes & Endocrinology (Garvey et al.). The trial was a Phase 2, randomized, double-blind, placebo-controlled study run at 32 sites in Poland, Romania and the United States. Of 493 adults randomized (485 received at least one dose), people were assigned 5:1 to one of five weekly petrelintide maintenance doses or to placebo. Everyone started at a low dose, escalated in fixed four-week steps, and received lifestyle counseling aimed at a deficit of about 500 calories per day. Participants had obesity (BMI of 30 or more) or overweight (BMI 27 or more) with high blood pressure or abnormal blood lipids, and none had type 2 diabetes (summary: Pharmacy Times).

Weight loss, shown both ways

Because trials of weight-loss drugs can be read two ways, the figures below are labeled by what they actually measure.

• Primary endpoint (week 28): average weight loss of 7.9% to 9.8% across the five doses versus 1.7% with placebo, with P<0.0001 for every dose.
• Dose response plateaued: the three higher doses produced similar results (by the on-treatment measure, 10.7%, 10.5% and 10.2%), so more drug did not mean more weight loss.
• Responder rates (exploratory): 34% to 56% of people on petrelintide had lost at least 10% of body weight by week 42, versus 9% on placebo.
• Cardiometabolic markers (some post hoc): systolic blood pressure fell by about 2.8 to 4.0 mm Hg, and the inflammation marker hs-CRP fell by up to 41% versus 6% on placebo. These are secondary and should not be treated as proof of cardiovascular benefit.

The efficacy figures come from the developer’s poster of the data, and the treatment-policy figure from the developer’s announcement as reported by Pharmacally.

Tolerability and safety

• Nausea: 6% on petrelintide versus 6.2% on placebo (12.3% to 28.0% depending on dose); about three-quarters of stomach events were mild and most happened during dose escalation.
• Other stomach effects: vomiting 3.0% versus 6.2% on placebo; diarrhea 7.4% in both groups; constipation 6.9% versus 3.7%.
• Stopping because of stomach effects: 5% on petrelintide and none on placebo. Overall, 15.5% left the trial early for any reason by week 42 (9.6% to 18.3% across drug doses; 24.7% on placebo).
• Serious events: serious adverse events occurred in 3.5% on drug versus 3.7% on placebo. Three were judged related to the drug: two cases of gallstone disease and one case of pancreatitis from a blocked bile duct. There were no deaths. Gallbladder and pancreas problems are also known concerns with GLP-1 medications, so they are worth watching in larger trials.
• Hair loss: about 5% on petrelintide versus about 1% on placebo (4.7% versus 1.2% in the poster). Our post on hair and skin changes with GLP-1 weight loss explains the common causes of shedding during rapid weight loss.
• Antibodies: 38% of treated participants developed antibodies against the drug, with no apparent effect on weight loss in this trial; the long-term meaning is unknown.

Limitations

• No head-to-head data. Petrelintide was compared only with placebo. Putting its ~10% next to results from Wegovy, Zepbound or CagriSema trials mixes different populations, durations and designs; the authors themselves caution against it. For context on what direct comparison looks like, see our explainer on the tirzepatide versus semaglutide trial.
• Phase 2, 42 weeks. Longer trials in more varied populations are needed. About 86% of participants were White, and only 4% had a BMI between 27 and 30.
• Dose groups were not masked from one another, and the dropout rate was higher on placebo (24.7%) than at any drug dose, which complicates reading the completer results.
• Body composition is unreported in the sources checked. Whether the weight lost is mostly fat is an open question for any weight-loss drug; see our piece on preserving muscle on GLP-1 therapy.
• Sponsor-run trial. Several data points come from the developer’s own materials; the paper itself should be consulted for the complete tables.

BeLite Clinical Perspective

Petrelintide is encouraging but early. It shows that an amylin-only drug can produce meaningful weight loss with a low rate of stopping for stomach reasons, which supports the idea that amylin could become a building block for combinations with GLP-1 drugs. It does not show that it works better, or is better tolerated, than the medications our patients use today, and it is years from the clinic: Phase 3 trials have only begun, and the newer drugs already in late-stage trials will reach patients first. Anyone offering petrelintide now, including as a compounded or “research” product, is selling something that has not been approved and has not been shown to be safe in the long term.

For patients today, the practical lesson is that the effective approved options are on the BeLite medications page. If side effects are the barrier, there are established strategies: slower titration, dose adjustment, meal pattern changes, and switching agents under physician supervision.

FAQs

Q: What is petrelintide?

A: Petrelintide is an investigational once-weekly injection that mimics amylin, a hormone that slows stomach emptying and promotes fullness. It is being developed by Zealand Pharma with Roche and is not approved by the FDA.

Q: How much weight did people lose?

A: At 42 weeks, up to 10.2% of body weight when everyone assigned to the drug is counted, and up to 10.7% in people while they stayed on it, compared with about 1.4% to 1.7% on placebo. Individual results varied, and 34% to 56% lost at least 10%.

Q: Does petrelintide cause less nausea than GLP-1 drugs?

A: Not shown. Nausea occurred in about 20% on petrelintide versus 6% on placebo, and no trial has compared it with a GLP-1 drug. The low rate of stopping for stomach reasons (1.5%) is promising, but it is not a head-to-head result.

Q: Is petrelintide related to CagriSema?

A: They share a mechanism. Both involve an amylin-type medicine, but petrelintide is a different molecule from the cagrilintide in CagriSema, and CagriSema pairs its amylin analog with semaglutide.

Q: When could petrelintide be available?

A: Not soon. The developer has announced a Phase 3 program of three trials, and approval would require those results and an FDA review. No approval date exists.

References

1. Garvey WT, Ard J, Connery L, et al. Petrelintide in adults with obesity or overweight: the ZUPREME-1 phase 2 trial. Lancet Diabetes Endocrinol. Published online September 29, 2026. DOI 10.1016/S2213-8587(26)00213-5.
2. Pharmacy Times. Petrelintide yields up to 10.7% weight loss with mild GI effects. October 6, 2026.
3. Garvey WT, et al. ZUPREME-1 poster and slides, ADA 2026 Scientific Sessions. Zealand Pharma.
4. Pharmacally. Petrelintide achieves double-digit weight loss with placebo-like GI profile in Phase 2 ZUPREME-1 trial.
5. BeLite Medical Center. CagriSema REDEFINE trials: weight loss results.
6. BeLite Medical Center. Our Medications.