SharpyPetrelintide: Roche and Zealand's Weekly Amylin Shot
Petrelintide is an experimental once-weekly amylin shot from Zealand Pharma and Roche, not a GLP-1. In the ZUPREME-1 phase 2 trial, adults without diabetes lost up to 10.7% of their weight at 42 weeks versus 1.7% on placebo, and on October 7, 2026, ZUPREME-2 showed up to 9.2% at 28 weeks in people with type 2 diabetes. Phase 3 trials with about 7,000 people have started, so it is not approved or available anywhere yet. While you wait for new drugs, Sharpy helps you keep muscle on today's GLP-1 with one protein target and one 20-minute workout a day.
What is petrelintide, and why is it back in the news? Petrelintide is an experimental once-weekly weight loss shot from Zealand Pharma and Roche. It copies amylin, a fullness hormone, instead of GLP-1. On October 7, 2026, Zealand reported that people with type 2 diabetes lost up to 9.2% of their weight in 28 weeks on it. That result went around again this week in coverage of amylin drugs. Petrelintide is not approved and cannot be prescribed. Phase 3 trials have just started.
Here is what it is, what the trials showed, and how it compares to drugs you can get today.
Petrelintide at a glance
| Petrelintide | |
|---|---|
| Code name | ZP8396 |
| Made by | Zealand Pharma (Denmark), partnered with Roche |
| Drug type | Long-acting amylin analog (not a GLP-1) |
| How it is taken | Injection under the skin, once a week |
| Best phase 2 result, no diabetes | Up to 10.7% weight loss at 42 weeks (placebo 1.7%) |
| Best phase 2 result, type 2 diabetes | Up to 9.2% at 28 weeks (placebo 2.0%) |
| Most common side effect | Nausea, 19.6% vs 6.2% on placebo (ZUPREME-1) |
| Stage | Phase 3 (ZUPREME-3, -4, -5), about 7,000 people |
| Approved anywhere? | No |
Petrelintide mechanism of action: how an amylin shot works
Your pancreas makes two hormones after a meal: insulin and amylin. Amylin tells your brain you have eaten enough. It also slows how fast food leaves your stomach.
Natural amylin lasts only minutes. Petrelintide is built to last about a week. Zealand says turning on amylin receptors helps restore the body's response to leptin, another fullness signal, so people feel full earlier in a meal.
GLP-1 drugs like semaglutide (Wegovy) and tirzepatide (Zepbound) also lower appetite, but through a different receptor. That is why drug makers are testing amylin drugs alone and paired with GLP-1s. Novo Nordisk's CagriSema pairs an amylin drug with semaglutide in one pen. Novo's amycretin puts both actions in one molecule.
Petrelintide phase 2 results: ZUPREME-1
ZUPREME-1 was the first big test. It enrolled about 490 adults with obesity or overweight and no diabetes at 32 sites in the US, Poland and Romania. Their average BMI was 36.7, and about half were women. People got one of five weekly doses or placebo, plus diet and exercise advice. The dose went up every four weeks for up to 16 weeks, then held steady.
| ZUPREME-1 result | Petrelintide | Placebo |
|---|---|---|
| Weight loss at 42 weeks | Up to 10.7% | 1.7% |
| Waist size | 7.9 to 10.8 cm smaller | 4.3 cm smaller |
| hsCRP (inflammation marker) | 17% to 41% lower | 6% lower |
| Triglycerides | 12% to 21% lower | 9% lower |
| Reached their target dose | 88% to 98% | n/a |
Two cautions. First, Healio reported that the 42-week results were exploratory; the main goal was measured at week 28. Second, the higher doses gave similar results, which suggests weight loss levels off around that range.
Petrelintide in type 2 diabetes: ZUPREME-2
ZUPREME-2 was the news on October 7, 2026. It enrolled 220 adults with obesity or overweight and type 2 diabetes in the US. They were already on metformin, some with an SGLT2 pill too. Average starting A1c was 8.0%.
| ZUPREME-2 result at 28 weeks | Petrelintide (3 doses) | Placebo |
|---|---|---|
| Weight loss | 7.4% to 9.2% | 2.0% |
| A1c change | Down up to 0.65 points | Up 0.23 points |
| Stopped for stomach side effects | 1.9% | 1.7% |
People with diabetes usually lose less weight on any drug, so 9.2% at 28 weeks is close to what ZUPREME-1 showed at the same point. The blood sugar drop was smaller than what GLP-1 drugs usually show, and Fierce Biotech noted that it fell short of rivals. Full results will be presented at a medical meeting later.
Petrelintide side effects
The pitch for amylin drugs is that they may be easier on the stomach than GLP-1s. Here is what ZUPREME-1 showed:
- Nausea: 19.6% on petrelintide vs 6.2% on placebo. The most common side effect.
- Vomiting: 3.0% vs 6.2%. Lower on the drug than on placebo.
- Diarrhea and constipation: under 7.5% in both groups.
- Severity: more than 75% of stomach side effects were mild.
- Stopping the drug for stomach issues: 1.5%.
For context, nausea hit about 44% of people on semaglutide 2.4 mg in STEP 1. Trials differ, so treat that as a rough guide, not a head-to-head result. If you are on a GLP-1 now and nausea is your problem, our guide to managing nausea has steps that work today.
Does petrelintide protect muscle?
People search "petrelintide lean mass" a lot, and the honest answer is that we do not know. Neither ZUPREME announcement reported body scans or lean mass. Any drug that makes you eat much less can cost you some muscle, unless you eat enough protein and lift.
That part you can control now, on any medication. Sharpy gives you one daily protein target based on your weight, one 20-minute strength workout, and a Shape Score that tracks your body, not just the scale. Our protein target guide explains the math.
Petrelintide vs cagrilintide, eloralintide and tirzepatide
Petrelintide is one of three weekly amylin shots in late-stage testing. Here is how the published numbers line up. These come from separate trials with different people and lengths, so they are not a direct comparison.
| Drug (maker) | Type | Best reported weight loss | Stage |
|---|---|---|---|
| Petrelintide (Zealand, Roche) | Amylin analog | Up to 10.7% at 42 weeks | Phase 3 |
| Cagrilintide alone (Novo Nordisk) | Amylin analog | 11.8% at 68 weeks (REDEFINE 1, alone arm) | Part of CagriSema, filed with FDA |
| Eloralintide (Eli Lilly) | Amylin receptor agonist | Up to 20.1% at 48 weeks | Phase 3 |
| Semaglutide 2.4 mg (Wegovy) | GLP-1 | 14.9% at 68 weeks (STEP 1) | Approved |
| Tirzepatide 15 mg (Zepbound) | GLP-1/GIP | 20.9% at 72 weeks (SURMOUNT-1) | Approved |
The petrelintide, cagrilintide and eloralintide numbers count people who stayed on the drug. The Wegovy and Zepbound numbers count everyone who started, which makes them look a little lower than they would on the same basis. Lilly is also testing eloralintide together with tirzepatide; see our EloraTZP guide for those results.
On paper, petrelintide loses less weight than eloralintide or tirzepatide. Zealand and Roche are betting on two other things: fewer stomach side effects, and pairing it with Roche's GLP-1/GIP drug CT-388 (enicepatide). A phase 2 trial of that combination is planned for the second half of 2026. For the full field of approved drugs, see our GLP-1 medication comparison.
Petrelintide phase 3: ZUPREME-3, -4 and -5
Zealand and Roche started phase 3 in 2026. The three trials together aim to enroll about 7,000 people:
- ZUPREME-3: obesity or overweight, no type 2 diabetes.
- ZUPREME-4: obesity or overweight with type 2 diabetes.
- ZUPREME-5: obesity or overweight with heart disease.
Zealand says the first participants have started treatment. The companies have not given a filing date. Big weight loss trials usually run more than a year, so do not expect petrelintide in pharmacies soon.
Who owns petrelintide? The Roche deal
Roche signed on in March 2025. Zealand got $1.65 billion up front, with up to $5.3 billion in total if milestones are hit. The two companies split profits 50/50 in the US and Europe, and Roche pays royalties elsewhere. Roche will lead the combination work with CT-388.
The bottom line
Petrelintide is a weekly amylin shot that led to about 9% to 11% weight loss in phase 2, with less vomiting than most GLP-1 trials report. It is in phase 3 and years from approval, and we have no data on whether it protects muscle. Today, the drugs you can get are GLP-1s, and the muscle work is up to you. Sharpy keeps that simple: one protein number, one short workout, one Shape Score a day.
Sources
- Zealand Pharma, company announcement No. 54/2026, ZUPREME-2 topline results (Oct 7, 2026): https://www.inderes.fi/releases/zealand-pharma-announces-positive-phase-2-zupreme-2-topline-results-for-amylin-analog-petrelintide-in-people-with-overweight-or-obesity-and-type-2-diabetes
- Zealand Pharma, new ZUPREME-1 data at ADA 2026 (Jun 5, 2026): https://www.biospace.com/press-releases/new-data-from-phase-2-zupreme-1-trial-at-the-american-diabetes-association-2026-scientific-sessions-further-support-potential-of-petrelintide-to-redefine-the-weight-management-experience-for-people-living-with-overweight-and-obesity
- Healio, "Petrelintide, a novel amylin analog, induces 10% weight loss" (Jul 14, 2026): https://www.healio.com/news/endocrinology/20260714/petrelintide-a-novel-amylin-analog-induces-10-weight-loss-very-well-tolerated
- HCPLive, ZUPREME-2 results (Oct 7, 2026): https://www.hcplive.com/view/zupreme-2-petrelintide-outperforms-placebo-for-weight-loss-in-t2d-and-obesity
- Fierce Biotech, ZUPREME-2 analysis (Oct 2026): https://fiercebiotech.com/biotech/zealand-roches-intriguing-weight-loss-soured-blood-sugar-data
- Roche, Zealand Pharma petrelintide agreement (Mar 12, 2025): https://www.roche.com/media/releases/med-cor-2025-03-12
- Eloralintide phase 2, The Lancet 2025 (PubMed): https://pubmed.ncbi.nlm.nih.gov/41207310/
- Garvey et al., REDEFINE 1, NEJM 2025: https://www.nejm.org/doi/full/10.1056/NEJMoa2502081
- Wilding et al., STEP 1, NEJM 2021: https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
- Jastreboff et al., SURMOUNT-1, NEJM 2022: https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
Questions people ask
What is petrelintide?
Petrelintide (code name ZP8396) is a long-acting version of amylin, a hormone your pancreas releases with insulin after you eat. Amylin helps you feel full sooner. Zealand Pharma made petrelintide to be given as a once-weekly injection under the skin. Zealand and Roche are developing it together for weight loss.
How much weight do you lose on petrelintide?
In ZUPREME-1, adults with obesity or overweight and no diabetes lost up to 10.7% of their body weight at 42 weeks, versus 1.7% on placebo. In ZUPREME-2, people with type 2 diabetes lost 7.4% to 9.2% at 28 weeks, versus 2.0% on placebo. Both numbers come from company announcements and use the efficacy estimand, which counts people who stayed on the drug.
What are the side effects of petrelintide?
In ZUPREME-1, nausea was the most common side effect: 19.6% on petrelintide versus 6.2% on placebo. Vomiting was 3.0% versus 6.2%, and diarrhea and constipation were under 7.5% in both groups. More than 3 in 4 stomach side effects were mild, and 1.5% of people stopped the drug because of them.
Is petrelintide FDA approved?
No. As of October 24, 2026, petrelintide is not approved anywhere. Zealand and Roche started a phase 3 program (ZUPREME-3, -4 and -5) with about 7,000 people in total. Approval would come only after those trials finish and the companies file with regulators.
Is petrelintide a GLP-1?
No. Petrelintide works on amylin receptors, not GLP-1 receptors. Both hormones lower appetite, but through different signals. Roche also plans to test petrelintide together with its own GLP-1/GIP drug, CT-388 (enicepatide), in a phase 2 trial.
Is petrelintide oral?
No. Petrelintide is a once-weekly injection under the skin. Zealand built it to stay stable near neutral pH, which makes it easier to mix with other peptides in one shot. No pill version has been announced.
Does petrelintide preserve muscle?
There is no public human data on that yet. Zealand's ZUPREME-1 and ZUPREME-2 announcements did not report body composition or lean mass results. Until there is, assume any weight loss drug can cost you some muscle, and protect it with protein and strength training.