Amycretin vs Petrelintide: GLP-1/Amylin Co-Agonist vs Amylin Analogue
Amycretin vs petrelintide: about 22% weight loss at 26 weeks vs up to 10.7% at 42 weeks in Phase 2. See how the two amylin-based agents compare in the data.
Research reference only. The information in this article is a summary of peer-reviewed scientific literature. It does not constitute medical advice and is not intended to guide human use. See our full disclaimer.
Amycretin vs petrelintide is the clearest contrast in the amylin field: one investigational molecule combines GLP-1 and amylin receptor agonism in a single peptide, while the other is a long-acting, amylin-only analogue designed to be tolerated without an incretin partner. This comparison summarizes the mechanism, published trial data, tolerability signals, and regulatory status of each compound as of October 2026.
Research reference only. All information on this page is a summary of peer-reviewed scientific literature and does not constitute medical advice. See individual library profiles for full compound data.
Quick Answer: Amycretin (zenagamtide) is a unimolecular GLP-1 and amylin receptor co-agonist from Novo Nordisk that produced roughly 22% mean weight reduction at 26 weeks in a Phase 1b/2 trial, whereas petrelintide is a once-weekly selective amylin analogue from Zealand Pharma and Roche that produced up to 10.7% at 42 weeks in the Phase 2 ZUPREME-1 trial with gastrointestinal events similar to placebo. The two have not been compared head to head, and trial designs differ.
TL;DR:
- Amycretin activates GLP-1 and amylin receptors from one molecule; petrelintide activates amylin receptors only.
- Amycretin Phase 1b/2 (Lancet, PMID 39626360): about 22% weight reduction vs about 10.6% with semaglutide 2.4 mg at 26 weeks.
- Petrelintide Phase 2 ZUPREME-1 (NCT06662539): up to 10.7% at week 42 vs 1.7% with placebo, with placebo-like GI adverse event rates.
- Petrelintide's half-life is about 10 days in Phase 1 (PMID 42017294); its Phase 3a ZUPREME program began September 22, 2026.
- Both compounds are investigational and not eligible for 503A compounding.
| Attribute | Amycretin | Petrelintide |
|---|---|---|
| Developer | Novo Nordisk | Zealand Pharma and Roche |
| Receptor action | GLP-1 and amylin (single molecule) | Amylin (calcitonin receptor/RAMP complexes) |
| Headline weight-loss figure | About 22% at 26 weeks (Phase 1b/2) | Up to 10.7% at 42 weeks (Phase 2, efficacy estimand) |
| Formulations studied | Subcutaneous weekly; oral daily | Subcutaneous weekly |
| Development stage | Phase 3 obesity program (AMAZE) | Phase 3a ZUPREME program |
| Regulatory status | Investigational | Investigational |
Amycretin: mechanism and evidence base
Amycretin (NNC0385-0434, also called zenagamtide in later development) is a first-in-class unimolecular agonist of the glucagon-like peptide-1 (GLP-1) receptor and the amylin receptor. Unlike cagrilintide combined with semaglutide in a fixed-dose pairing, amycretin delivers both activities from one molecule. GLP-1 receptor activation acts on hypothalamic and brainstem appetite circuits, slows gastric emptying and supports glucose-dependent insulin secretion, while amylin receptor activation acts through the area postrema to reduce meal size and suppress glucagon. Full profile data are on the amycretin library page.
The primary dataset is the Phase 1b/2 randomized, double-blind, double-dummy trial published in The Lancet (PMID 39626360). Over 26 weeks in adults with overweight or obesity, subcutaneous amycretin produced approximately 22% mean body weight reduction compared with approximately 10.6% for semaglutide 2.4 mg. In a Phase 2 dose-finding study in type 2 diabetes (NCT06542874), zenagamtide 40 mg subcutaneously once weekly produced up to 14.6% weight loss at 36 weeks, and two companion Lancet papers in August 2026 reported HbA1c reductions of 0.9% to 1.7% in the subcutaneous arm (PMID 42532080) and up to 1.4% in the once-daily oral arm (PMID 42532079). Adverse events were mainly mild to moderate gastrointestinal events, and an oral formulation is also under study.
Petrelintide: mechanism and evidence base
Petrelintide (ZP8396, RG6849) is a long-acting human amylin analogue engineered for stability at neutral pH without fibrillation, a property that distinguishes it from native amylin and the short-acting analogue pramlintide and that makes co-formulation with other peptides feasible. It activates amylin receptors, which promote satiation, slow gastric emptying and suppress postprandial glucagon. The hypothesis behind amylin-only agents is weight reduction with fewer gastrointestinal effects than incretin-based approaches. See the petrelintide library profile for the full record.
In two Phase 1 trials (Diabetes, Obesity and Metabolism, 2026; PMID 42017294), petrelintide produced no serious or severe treatment-emergent adverse events, had a half-life of roughly 10 days, showed dose-proportional steady-state exposure, and reduced body weight by up to 8.6% after 16 weeks of once-weekly dosing. In the Phase 2 ZUPREME-1 trial (NCT06662539; 493 participants), mean weight loss reached up to 10.7% at week 42 versus 1.7% with placebo by the efficacy estimand, with waist circumference falling up to 10.8 cm versus 4.3 cm. The ZUPREME-2 trial (NCT06926842) in participants with type 2 diabetes reported topline weight loss of 7.4% to 9.2% at week 28 versus 2.0% with placebo, with GI-related discontinuations of 1.9% versus 1.7%.
Side-by-side comparison
The most important caution in comparing these compounds is that the trials differ in duration, population, estimand and dose escalation. Amycretin's 26-week figure comes from a smaller early-phase study with a semaglutide active comparator, while petrelintide's 42-week figure comes from a larger placebo-controlled Phase 2 study. Neither dataset supports a direct ranking. Amycretin's design adds GLP-1 pharmacology to amylin signaling, which is consistent with its larger early weight effect; petrelintide's design isolates the amylin pathway, which is consistent with its low GI discontinuation rates. Related amylin pairings are discussed in amycretin vs cagrilintide and petrelintide vs eloralintide.
Differential research applications
Researchers studying whether amylin receptor agonism alone is sufficient for durable weight reduction have used petrelintide-class analogues as a selective pharmacological tool, whereas those studying the additive value of GLP-1 and amylin signaling have focused on unimolecular or combined approaches such as amycretin. Petrelintide is also being evaluated in combination with Roche's dual GLP-1/GIP agonist enicepatide (NCT07589686), which tests the modular alternative to a single co-agonist molecule. Half-life differences between the two peptides can be reviewed in the half-life chart, and trial statuses can be followed on the clinical trial tracker.
Regulatory and compounding status
Neither compound holds regulatory approval in any jurisdiction as of October 2026. Amycretin is in the Phase 3 AMAZE obesity program, with a type 2 diabetes program planned. Petrelintide entered registrational Phase 3a development (ZUPREME-3, -4 and -5; roughly 7,000 participants combined) on September 22, 2026, with a primary endpoint of percentage change in body weight at week 64. As investigational peptides, neither is eligible for 503A compounding.
Cited studies
- PMID 39626360: "Subcutaneous amycretin versus semaglutide 2.4 mg in adults with overweight or obesity: a randomised, double-blind, double-dummy, phase 1b/2 trial" (The Lancet, 2025). https://doi.org/10.1016/S0140-6736(24)02496-8
- PMID 42017294: "Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Petrelintide for Weight Management: Two Randomized, Controlled Phase 1 Trials" (Diabetes, Obesity and Metabolism, 2026). https://doi.org/10.1111/dom.70753
- PMID 42532080 · Amycretin subcutaneous Phase 2 in type 2 diabetes (The Lancet, 2026).
- PMID 42532079 · Amycretin oral Phase 2 in type 2 diabetes (The Lancet, 2026).
Frequently asked questions
Q: What is the difference between amycretin and petrelintide?
A: Amycretin is a single molecule that activates both GLP-1 and amylin receptors, while petrelintide activates amylin receptors only. Amycretin is developed by Novo Nordisk and petrelintide by Zealand Pharma with Roche.
Q: Which produced more weight loss in trials, amycretin or petrelintide?
A: Amycretin showed about 22% at 26 weeks in a Phase 1b/2 trial, and petrelintide showed up to 10.7% at 42 weeks in Phase 2. The studies differ in design and population, so the figures are not directly comparable.
Q: Is petrelintide an amylin analogue like pramlintide?
A: Yes, both are amylin receptor agonists, but petrelintide is long-acting with a half-life of about 10 days and was engineered to avoid fibrillation at neutral pH. Pramlintide has a much shorter duration of action.
Q: Is amycretin the same as CagriSema?
A: No. CagriSema combines two separate molecules, cagrilintide and semaglutide, while amycretin delivers GLP-1 and amylin receptor agonism from one molecule.
Q: Are amycretin or petrelintide approved by the FDA?
A: Neither is approved as of October 2026. Both are investigational and in Phase 3 development, and neither is eligible for 503A compounding.
See also:
- Amycretin vs Cagrilintide: compares the unimolecular co-agonist with a selective amylin analogue.
- Petrelintide vs Eloralintide: two amylin-only agents side by side.
- Eloralintide vs Amycretin: another amylin versus dual-agonist contrast.
For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.