Petrelintide

ZP8396

Metabolic & weight
Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

1What it is

Petrelintide is Zealand Pharma's long-acting amylin analogue, designed as a weekly injection for obesity. Zealand (Denmark) also discovered lixisenatide and co-develops survodutide. In 2025 Roche entered a large collaboration with Zealand to co-develop and commercialise petrelintide, both alone and in combination with Roche's own incretin candidates †. That deal reflects the broader industry bet that amylin analogues could offer GLP-1-like weight loss with better tolerability and better preservation of lean mass.

The amylin class is small: pramlintide (profile 65) is the only approved member; cagrilintide (Novo Nordisk, in the CagriSema combination) is the most advanced investigational one; eloralintide (profile 67) is Lilly's. Petrelintide's claimed differences are a formulation stable at physiological pH, which matters for combining it in one pen with a GLP-1 drug, and a receptor profile closer to native amylin.


2How it's thought to work

Amylin is released with insulin after meals and signals to the brain that eating is under way. Petrelintide mimics this:

Satiety. acts on area postrema and hypothalamic amylin receptors to reduce meal size and food intake, a mechanism reported to involve less nausea than GLP-1 agonism at equivalent weight loss.
Gastric emptying and glucagon. slows emptying and suppresses post-meal glucagon.
Leptin sensitivity. amylin agonism appears to restore leptin responsiveness in obesity, which may help weight loss persist.
Lean mass hypothesis. early industry data suggest amylin analogues may lose proportionally less lean mass than GLP-1 ; this is a hypothesis under test, not established.
A long-acting amylin analogue being developed alongside and in combination with GLP-1 agonists, on the view that the two appetite signals are additive.Schematic — not to scale

3What the research shows

Graded B (phase 1)

Weight loss in overweight/obesity

A randomised, placebo-controlled multiple-ascending-dose phase 1 study in adults with overweight or obesity reported mean weight loss of approximately 8.3% after 16 weeks at the highest dose cohort, versus about 1.7% with placebo, with GI adverse events described as mostly mild and transient and no apparent plateau at 16 weeks (Zealand Pharma announcement 2024; presented at scientific congresses; peer-reviewed publication †). Phase 1 data from a company are graded B here regardless of randomisation, per this site's standard. [1]
Not gradedgrade pending

Phase 2b — ZUPREME-1 and ZUPREME-2

ZUPREME-1 (adults with overweight or obesity without diabetes, ~480 participants, 28-week maintenance phase) and ZUPREME-2 (type 2 diabetes) began in 2024–2025. Zealand/Roche have guided to ZUPREME-1 results in 2026 †. Until published, no grade above B is justified.
Graded D/planned

Combination with incretins

Roche's stated plan is to combine petrelintide with its GLP-1/GIP CT-388 and others. No human combination data have been published †.

Lean mass, nausea comparison with GLP-1 agonists

Frequently claimed advantages for the class; not yet shown in a controlled comparison for petrelintide.

4Reported side effects and interactions

Literature-reported

nausea, vomiting, decreased appetite and other GI effects, reported as mostly mild to moderate in phase 1; injection-site reactions. No serious safety signal reported publicly, but exposure is small and short.

Community-reported

very limited; petrelintide is not yet widely available in the grey market. Any product sold under this name should be treated as of uncertain identity.

Theoretical (class). amylin analogues slow gastric emptying and could delay oral drug absorption; pramlintide's experience suggests any added hypoglycaemia risk comes only in combination with insulin. Long-term effects on the calcitonin receptor (bone, calcium handling) are a theoretical question for all compounds in this class and have not been characterised for petrelintide. Anti-drug antibodies †.

Interactions. none established. Likely additive with GLP-1 (the intended combination).

Markers researchers commonly monitor

No compound-specific markers are established; the trial protocols and class physiology suggest:

MarkerWhy it's watched
Weight, waist circumference and body composition (DEXA/bioimpedance)the lean-mass question is the key one for this class.
HbA1c and fasting glucoseamylin analogues improve post-meal glucose; relevant in ZUPREME-2.
Serum calcium and bone markersa theoretical calcitonin-receptor consideration; not routinely needed but a baseline is reasonable in long-term use.
Lipid panel and blood pressureexpected to improve with weight loss.
eGFR and creatininedehydration from GI effects.
CBC and CMPgeneral baseline for an investigational injected compound.

Free for everyone. Safety information is never behind a paywall.


5Reconstitution and handling

Investigational product; trial material is a liquid formulation stable at neutral pH. If grey-market material is encountered, standard practice applies: with , swirl gently, refrigerate, protect from light. Dose units in trials are milligrams; the calculator helps avoid unit confusion.

Open in calculator, pre-loaded →

6Commonly studied alongside

Planned with CT-388 (GLP-1/GIP). Class comparators: cagrilintide (and CagriSema with semaglutide), eloralintide, pramlintide. Community discussion sometimes pairs amylin analogues with semaglutide or tirzepatide, mirroring CagriSema; there is no petrelintide trial of this.

Informational cross-links. Not stack recommendations.


7Regulatory status by region

RegionStatus (checked —)
United StatesNot FDA-approved; investigational (IND). Not permitted for compounding
European UnionNot authorised; investigational
United KingdomNot licensed
AustraliaNot approved
South AfricaNot registered
SportNot specifically listed by WADA; as a non-approved substance it falls under S0 †

8Open questions

  • Does the phase 1 trajectory hold at 28 and 52 weeks, and what is the plateau?
  • Is lean-mass preservation real when measured by DEXA against a GLP-1 comparator?
  • Tolerability versus semaglutide at matched weight loss.
  • Whether a fixed-dose combination with a GLP-1/GIP adds materially beyond either alone.

9References

  1. 1Zealand Pharma (2024). Petrelintide (ZP8396) phase 1 multiple-ascending-dose results in adults with overweight or obesity — company announcement and congress presentation [verify peer-reviewed publication]. PubMed
  2. 2Zealand Pharma / Roche (2025). Collaboration and co-development agreement for petrelintide — press release [verify]. PubMed
  3. 3ClinicalTrials.gov. ZUPREME-1 and ZUPREME-2: phase 2 trials of petrelintide in overweight/obesity and type 2 diabetes [verify identifiers]. PubMed
  4. 4Hay DL et al. (2015). Amylin: pharmacology, physiology, and clinical potential. Pharmacol Rev. PubMed · DOI
  5. 5Boyle CN, Lutz TA, Le Foll C (2018). Amylin — its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity. Mol Metab. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.


10Community

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

26 Oct 2026Profile published — awaiting medical review

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