Petrelintide
Also known as: NN-unknown (Zealand Pharma amylin analogue), long-acting human amylin analogue
Long-acting amylin analogue; Dual amylin receptor (AMYR) / calcitonin receptor (CTR) agonist
What it is
Petrelintide is a potent, stable, long-acting analogue of human amylin engineered for formulation at approximately neutral pH. It acts as a dual agonist at the amylin receptor (AMYR) and calcitonin receptor (CTR). Like native amylin, it promotes satiation through central nervous system mechanisms, slows gastric emptying, and suppresses glucagon secretion (PMID 42452898; PMID 42586227). Its pharmacological and neural mechanisms are described as distinct from incretin-based (GLP-1R) therapies (PMID 42586227; PMID 42810355). Advances in peptide engineering enabled a half-life of approximately 10 days in humans, supporting once-weekly subcutaneous dosing.
Class: Long-acting amylin analogue; Dual amylin receptor (AMYR) / calcitonin receptor (CTR) agonist
What it's studied for
- Weight management / obesity Human RCT
- Multicentre, randomised, double-blind, placebo-controlled phase 2 trial (n=485 receiving ≥1 dose). Once-weekly subcutaneous petrelintide (1.0–9.0 mg maintenance doses) over 42 weeks (including dose escalation). Mean bodyweight change from baseline at 28 weeks ranged from -7.9% (1.0 mg and 2.5 mg) to -9.8% (5.0 mg) vs - PMID 42810355 Garvey et al., The Lancet Diabetes & Endocrinology (2026) — ZUPREME 1 phase 2 RCT
- Two randomised, placebo-controlled, double-blind phase 1 trials. MAD part 2 (adults with overweight/obesity): 16 once-weekly SC doses escalated every 2 weeks to target doses of 2.4, 4.8, and 9.0 mg; body weight reduced by up to 8.6% after 16 weeks. No serious or severe TEAEs. PMID 42017294 Brændholt Olsen et al., Diabetes, Obesity & Metabolism (2026) — Phase 1 SAD/MAD trials
- Type 2 diabetes management (context: amylin analogue class) Animal studies only
- Narrative review notes petrelintide is among long-acting amylin analogues showing strong efficacy as monotherapy in clinical trials for obesity and type 2 diabetes management; specific petrelintide T2D trial data not reported in this abstract. PMID 41747885 Bailey et al., Peptides (2026) — Review
- Potential combination therapy for obesity (preclinical/early clinical context) Mixed
- Petrelintide was developed with the ability to be formulated at about neutral pH, enabling potential coformulation with currently marketed drugs as a combination therapy for weight management. PMID 41217931 Munch et al., Journal of Medicinal Chemistry (2025)
- Review notes petrelintide has demonstrated clinically meaningful weight loss with generally favorable tolerability profiles as both a standalone and combination approach. PMID 42452898 Alhazmi & le Roux, Diabetes, Obesity & Metabolism (2026) — Review
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Subcutaneous (primary); intravenous (single dose in SAD) | Single ascending doses: 0.04–2.4 mg SC; 0.35 mg IV (SAD trial). Multiple ascending doses: 0.6 mg and 1.2 mg once-weekly SC for 6 doses (MAD part 1); escalated every 2 weeks to target doses of 2.4, 4.8, and 9.0 mg once-weekly SC for 16 doses (MAD part 2) | SAD: single dose; MAD part 1: 6 weeks; MAD part 2: 16 weeks | human | Research PMID 42017294 |
| Subcutaneous (self-administered) | Maintenance doses of 1.0, 2.5, 5.0, 7.0, or 9.0 mg once-weekly SC (with dose escalation phase included in 42-week treatment period) | 42 weeks (including dose escalation); primary endpoint at 28 weeks | human | Research PMID 42810355 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Nausea (most common TEAE): occurred in 16.7%–33.3% of petrelintide participants vs 16.7% placebo in phase 1 MAD part 2; 20% of petrelintide participants vs 6% placebo in phase 2 ZUPREME 1. Described as predominantly mild and occurring during dose escalation. PMID 42017294
- Nausea reported in 79/404 (20%) petrelintide participants vs 5/81 (6%) placebo participants in phase 2 trial. PMID 42810355
- Vomiting: one phase 1 participant discontinued treatment due to GI TEAEs including vomiting; otherwise rare. PMID 42017294
- Vomiting infrequent in phase 2 (3% petrelintide vs 6% placebo); diarrhoea similarly low between active treatment and placebo (7% vs 7%); constipation 7% vs 4%. PMID 42810355
- Gastrointestinal side effects (nausea, GI disorders) described as commonplace during initiation and up-titration of amylin analogues as a class, but mostly resolve during continued use. PMID 41747885
- No serious or severe treatment-emergent adverse events reported across phase 1 SAD and MAD trials. PMID 42017294
- No deaths reported in the phase 2 ZUPREME 1 trial. PMID 42810355
Contraindications
- Phase 2 ZUPREME 1 trial excluded individuals with type 2 diabetes (enrolled adults without type 2 diabetes); applicability in this population is not established from reviewed literature. PMID 42810355
Frequently asked
What is petrelintide and how does it work?
Petrelintide is a long-acting analogue of human amylin, a hormone co-secreted with insulin from pancreatic β-cells. It acts as a dual agonist at the amylin receptor (AMYR) and calcitonin receptor (CTR), promoting satiation through central nervous system mechanisms, slowing gastric emptying, and suppressing glucagon secretion. It has a half-life of approximately 10 days, supporting once-weekly subcutaneous dosing. Its mechanism is described as distinct from GLP-1-based therapies (PMID 41217931; PMID 42017294; PMID 42586227; PMID 42810355).
What weight loss has been seen with petrelintide in clinical trials?
In the phase 2 ZUPREME 1 trial (n=485 receiving ≥1 dose, 42 weeks), once-weekly subcutaneous petrelintide at maintenance doses of 1.0–9.0 mg produced mean bodyweight reductions of -7.9% to -9.8% from baseline at 28 weeks, versus -1.7% with placebo. Weight continued to decline to week 42, with reductions of up to -10.7%. In phase 1 MAD trials, up to 8.6% body weight reduction was observed after 16 weeks.
What dose of petrelintide should I take?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: Phase 2 trials used once-weekly subcutaneous maintenance doses of 1.0, 2.5, 5.0, 7.0, or 9.0 mg with a dose escalation period over 42 weeks in adults with obesity. Phase 1 MAD trials escalated to target doses of 2.4, 4.8, and 9.0 mg once weekly.
Is petrelintide FDA approved?
The reviewed scientific literature does not state the current FDA approval status of petrelintide. As of the published abstracts available, petrelintide was described as in clinical development (phase 2 trials reported in 2026) (PMID 42810355; PMID 42017294). Regulatory status requires manual verification from official FDA sources.
What are the side effects of petrelintide?
In clinical trials, the most common side effect was nausea, which occurred in 20%–33% of petrelintide-treated participants (vs 6%–17% placebo) and was predominantly mild and associated with dose escalation. Vomiting was infrequent, and diarrhoea rates were similar between petrelintide and placebo. One participant in phase 1 discontinued due to GI adverse events. No serious or severe adverse events and no deaths were reported in the reviewed trials (PMID 42017294; PMID 42810355).
Can I combine petrelintide with semaglutide or other peptides?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: Petrelintide has been studied as a monotherapy in phase 1 and phase 2 trials (PMID 42017294; PMID 42810355). Its neutral-pH formulation was noted as enabling potential coformulation with other drugs, but no specific combination trial data for petrelintide are reported in the reviewed abstracts. Separate combination approaches (e.g., cagrilintide + semaglutide) exist in the amylin class but are distinct agents.
How is petrelintide administered?
In clinical trials, petrelintide was administered as a once-weekly subcutaneous (SC) self-injection. An intravenous route was used in one cohort of the phase 1 SAD trial only. The phase 2 trial used self-administered subcutaneous injections (PMID 42017294; PMID 42810355). Specific reconstitution instructions are not described in the reviewed abstracts.
Is petrelintide better than semaglutide or other GLP-1 drugs?
No head-to-head comparative trial between petrelintide and semaglutide is reported in the reviewed abstracts. Petrelintide works through a distinct mechanism (amylin/calcitonin receptor agonism) compared with GLP-1 receptor agonists, and reviews suggest its tolerability profile — particularly lower rates of nausea and vomiting in some comparisons — may differ (PMID 42586227; PMID 42452898). Direct efficacy comparisons require head-to-head trial data not available in reviewed literature.
Can petrelintide be used for type 2 diabetes?
I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider. What is noted in the reviewed literature: the phase 2 ZUPREME 1 trial explicitly excluded people with type 2 diabetes, enrolling only adults without T2D. A review mentions petrelintide among agents being evaluated for obesity and type 2 diabetes, but no petrelintide-specific T2D trial data are reported in the reviewed abstracts.
Where can I buy petrelintide?
I don't recommend vendors or sources. Please consult a licensed provider. As of the reviewed literature, petrelintide was in clinical development (phase 2 trials) and not described as commercially available.
References
- [1] PMID 42810355 — Multicentre, randomised, double-blind, placebo-controlled phase 2 trial (n=485 receiving ≥1 dose). Once-weekly subcutaneous petrelintide (1.0–9.0 mg maintenance
- [2] PMID 42017294 — Two randomised, placebo-controlled, double-blind phase 1 trials. MAD part 2 (adults with overweight/obesity): 16 once-weekly SC doses escalated every 2 weeks to
- [3] PMID 41747885 — Narrative review notes petrelintide is among long-acting amylin analogues showing strong efficacy as monotherapy in clinical trials for obesity and type 2 diabe
- [4] PMID 41217931 — Petrelintide was developed with the ability to be formulated at about neutral pH, enabling potential coformulation with currently marketed drugs as a combinatio
- [5] PMID 42452898 — Review notes petrelintide has demonstrated clinically meaningful weight loss with generally favorable tolerability profiles as both a standalone and combination
- [6] PMID 40608546 — in-prose reference
- [7] PMID 42586227 — in-prose reference