Peptide education
Petrelintide
ZP8396 · ZP-8396
Petrelintide is a long-acting analog of amylin, a hormone involved in fullness and food intake. Researchers are studying it as a once-weekly injection for weight management. It is a different molecule and pathway from a GLP-1 receptor agonist.
Petrelintide produced greater average weight reduction than placebo in a published phase 2 study. Nausea occurred more often with petrelintide, and longer-term safety and phase 3 outcomes remain to be established.
Overview
Quick answer
The published ZUPREME-1 trial enrolled adults without type 2 diabetes. ZUPREME-2 studied adults with type 2 diabetes, but its public results are a sponsor topline report. Both are phase 2 studies.
What is petrelintide being studied for?
Researchers are studying chronic weight management in adults with overweight or obesity. The trials distinguish people with type 2 diabetes from those without it.
How much weight changed in the published trial?
At 28 weeks, mean weight change across the five active groups ranged from minus 7.9% to minus 9.8%, compared with minus 1.7% for placebo. These are group averages from the trial's efficacy analysis.
Is petrelintide approved in the United States?
No FDA-approved product was found in the Drugs@FDA ingredient search. The phase 3 studies are investigations, not evidence of approval.
Are there phase 3 trials?
Yes. Registrations describe separate studies for participants without type 2 diabetes, participants with type 2 diabetes, and participants with established cardiovascular disease. Their registration does not mean results are available.
What side effects were reported?
In ZUPREME-1, nausea was reported by 20% of participants across the active groups and 6% of the placebo group. Vomiting, diarrhea, and constipation were also recorded. Rare and longer-term risks remain less certain.
Evidence
Evidence snapshot
ZUPREME-1 enrolled adults without type 2 diabetes and compared five maintenance doses with placebo. Its primary weight endpoint was at week 28.
The sponsor described 220 adults with type 2 diabetes; the trial registry lists 221 enrolled. The sponsor reported 7.4% to 9.2% mean weight reduction across active groups versus 2.0% with placebo at week 28. Full trial reporting remains important.
In ZUPREME-1, nausea was reported by 20% receiving petrelintide and 6% receiving placebo. The active groups were pooled for this comparison.
The Drugs@FDA ingredient search returned no match. The EMA medicines table also had no match for centralized authorization; national authorizations outside that table were not established.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Petrelintide has been shown to reduce weight in a controlled trial. | In ZUPREME-1, each active group had a larger average reduction than placebo at the primary 28-week assessment. The greatest reported reduction by week 42 was 10.7% in an active group. | The candidate is an amylin analog, a different approach from GLP-1 receptor agonism. A biological rationale is not a substitute for outcomes. | Supported for the trial's adults without type 2 diabetes, within the duration and conditions studied. Longer-term and phase 3 outcomes are pending. |
| The diabetes trial is the same evidence as ZUPREME-1. | ZUPREME-2 enrolled adults with type 2 diabetes taking metformin, with or without an SGLT2 inhibitor. Its sponsor has released topline findings; ZUPREME-1 is a published trial in adults without type 2 diabetes. | No. Population and evidence maturity differ, so the two results should be read separately. | |
| Petrelintide caused no more nausea than placebo. | ZUPREME-1 reported nausea in 79 of 404 participants receiving petrelintide and five of 81 receiving placebo. | The trial does not support that claim. Nausea was more frequent in the active groups, even though other gastrointestinal event rates differed. |
Bottom line
Main takeaway
Petrelintide is an experimental amylin analog. There is no FDA-approved petrelintide weight-management medicine in the ingredient search.
Compare the active groups with placebo at the same time point, and keep the published non-diabetes trial separate from the sponsor's diabetes-population announcement.
ZUPREME-1 used an efficacy estimand and studied treatment for 42 weeks. Full ZUPREME-2 reporting and longer phase 3 outcomes will add context on durability and safety.
Identity
What it is
Petrelintide, also known as ZP8396, was designed as a long-acting amylin analog. Amylin is released with insulin after eating and contributes to signals that help regulate food intake.
The clinical program studies petrelintide alone in several populations. A separate combination approach has been proposed, but results from a combination cannot be treated as results for petrelintide alone.
Use context
Routes, doses, and cycle patterns
ZUPREME-1 and ZUPREME-2 used once-weekly treatment assignments in different groups of participants.
Human studies and product labels
ZUPREME-1 maintenance groups
- Purpose
- Weight-management research without type 2 diabetes
- Context
- Randomized phase 2 trial compared with placebo
- Route
- Subcutaneous
- Amount
- 1, 2.5, 5, 7, or 9 mg maintenance doses after escalation
- Frequency
- Once weekly
- Duration
- 42 weeks including escalation; primary endpoint at week 28
The sponsor described escalation every four weeks for up to 16 weeks, followed by maintenance to week 42. These are study doses, not an approved regimen.
ZUPREME-2
- Purpose
- Weight-management research with type 2 diabetes
- Context
- Randomized phase 2 trial; sponsor topline report
- Route
- Subcutaneous
- Amount
- Three active dose groups; specific amounts are not stated in the cited topline report
- Frequency
- Once weekly
- Duration
- 28 weeks of treatment including escalation
Participants were taking metformin, with or without an SGLT2 inhibitor. The sponsor reported escalation every four weeks for up to 16 weeks, followed by maintenance to week 28.
What varies
- Population: the two phase 2 studies differ in type 2 diabetes status.
- Timing: week 28 was the primary ZUPREME-1 assessment; treatment continued to week 42.
- Dose: the listed amounts are ZUPREME-1 maintenance arms after escalation.
Research
Research evidence
ZUPREME-1 reported a placebo-controlled weight reduction in adults without type 2 diabetes. The sponsor reported a separate positive weight result in adults with type 2 diabetes in ZUPREME-2. The second report is topline evidence, and the phase 3 registrations do not yet provide finished outcomes.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| ZUPREME-1 | 493 randomized adults without type 2 diabetes and with obesity or qualifying overweight | Randomized, placebo-controlled phase 2 study | Five once-weekly subcutaneous maintenance arms after escalation | At week 28, average weight change ranged from minus 7.9% to minus 9.8% across active arms versus minus 1.7% with placebo. At week 42 the largest reported active-group reduction was 10.7%. | The efficacy analysis is a group estimate. Treatment assignment was masked, but maintenance dose was not masked; the trial does not establish long-term safety. | Controlled human phase 2 trial |
| ZUPREME-2 | Sponsor described 220 adults with overweight or obesity and type 2 diabetes; registry lists 221 enrolled | Randomized, placebo-controlled phase 2 study | Once-weekly petrelintide or placebo with background diabetes treatment | The sponsor reported mean weight reduction of 7.4% to 9.2% across active groups versus 2.0% with placebo at week 28 using the efficacy estimand. | These are sponsor topline results, not a full peer-reviewed report. | Controlled study with sponsor-reported results |
| Phase 3 program | Separate groups without type 2 diabetes, with type 2 diabetes, and with established cardiovascular disease | Registered placebo-controlled phase 3 studies | Investigational petrelintide | Studies have been registered and are in progress. | Registration is not proof of completed efficacy or safety outcomes. | Trial registrations, outcomes pending |
Use context
Reported use context
ZUPREME-1 and ZUPREME-2 studied once-weekly treatment in separate groups of adults with overweight or obesity.
Study and label context
Once-weekly maintenance groups of 1, 2.5, 5, 7, or 9 mg after escalation every four weeks for up to 16 weeks, with placebo comparison.
Study-reported in adults without type 2 diabetes.Once-weekly treatment in three active groups versus placebo for 28 weeks, including escalation every four weeks for up to 16 weeks.
Sponsor-reported trial in adults with type 2 diabetes.Cautions
Safety and unknowns
- Nausea was reported in 20% of pooled petrelintide participants versus 6% on placebo in ZUPREME-1. Vomiting was reported in 3% versus 6%, diarrhea in 7% versus 7%, and constipation in 7% versus 4%. These are trial reports, not guarantees for a future patient.
- ZUPREME-1 treated participants for 42 weeks. It cannot settle rare adverse events, effects after longer treatment, or safety in populations underrepresented or excluded from the trial.
- In ZUPREME-2, the sponsor reported discontinuation due to gastrointestinal adverse events in 1.9% receiving petrelintide and 1.7% receiving placebo. Full reporting is needed to assess the diabetes-population safety data.
Product quality
Product identity and quality
A controlled clinical-trial product is not interchangeable with an independently sourced vial just because both use the same compound name. The trial results do not verify another product's contents.
Identity and concentration
A product name alone does not establish that the substance or amount matches material studied in a clinical trial.
Sterility and storage
Injectable products require appropriate manufacturing, handling, and storage; a trial result does not verify those controls elsewhere.
Mechanism
How it is proposed to work
Amylin is a hormone involved in fullness. Petrelintide was designed as a longer-acting amylin analog, so researchers are testing whether its effects on appetite translate into meaningful weight outcomes.
Amylin signaling and GLP-1 signaling are distinct. Interest in combining the pathways does not establish that any particular combination is effective or safe.
FAQ
Common questions
Is petrelintide FDA-approved?
No FDA-approved product was found in the active-ingredient search. Petrelintide remains in clinical development.
Was nausea the same as placebo in the main trial?
No. Nausea was reported in 20% of the pooled petrelintide groups and 6% of the placebo group in ZUPREME-1.
Details
Technical details
Sources
References
- 1.
PubMed. Petrelintide in the ZUPREME 1 randomized phase 2 trial
doi:10.1016/S2213-8587(26)00213-5 PMID:42810355 NCT06662539
Peer-reviewed trial in adults with overweight or obesity without type 2 diabetes.
- 2.
Roche. Roche ZUPREME-1 phase 2 trial results announcement
NCT06662539
Sponsor report describes escalation every four weeks for up to 16 weeks before maintenance to week 42.
- 3.
ClinicalTrials.gov. ZUPREME-2 trial registry
NCT06926842
Completed phase 2 trial in adults with overweight or obesity and type 2 diabetes.
- 4.
Zealand Pharma. ZUPREME-2 sponsor topline results
Sponsor-reported results, distinct from a full peer-reviewed publication.
- 5.
ClinicalTrials.gov. Phase 3 petrelintide trial in overweight or obesity without type 2 diabetes
NCT07843498
ZUPREME-3 phase 3 registration; study status may change.
- 6.
ClinicalTrials.gov. Phase 3 petrelintide trial in overweight or obesity with type 2 diabetes
NCT07843485
ZUPREME-4 phase 3 registration; study status may change.
- 7.
ClinicalTrials.gov. Phase 3 petrelintide trial in overweight or obesity with cardiovascular disease
NCT07843472
ZUPREME-5 phase 3 registration; study status may change.
- 8.
FDA. Drugs@FDA active ingredient search for petrelintide
The openFDA Drugs@FDA ingredient search returned no match. The linked FDA search can be used to recheck; database coverage has limits.
- 9.
European Medicines Agency. EMA medicines data table
No petrelintide match in the downloaded EMA table; it does not establish every national authorization.