Evidence Grade E — Very limited evidence. 4 published studies. 5 registered clinical trials.
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Petrelintide is a long-acting amylin analogue from Zealand Pharma, competing with cagrilintide in the amylin space. It has a longer half-life (about 10 days versus 7) and is chemically stable without the tendency to form clumps — a manufacturing and safety advantage. Its primary strategic value is as a combination partner with GLP-1 drugs.
Petrelintide is also known by these brand and alternate names:
4 published studies: 3 human, 0 animal, 2 in-vitro, 1 reviews
Petrelintide is in Phase II development (not yet approved). Phase Ib results (48 patients, 16 weeks) showed up to 8.6% weight loss. No serious adverse events or anti-drug antibodies were detected. A Phase IIb trial is ongoing.
Petrelintide's primary strategic interest is as a potential partner for combination with GLP-1 agonists, similar to how cagrilintide is combined with semaglutide in CagriSema (#162). Zealand Pharma is also developing it in combination with survodutide.
Petrelintide activates amylin receptors and the calcitonin receptor, promoting satiety through brain pathways that complement GLP-1 signalling. Its chemical stability (no fibrillation tendency) differentiates it from native amylin and some analogues, which are prone to forming insoluble aggregates that complicate manufacturing and storage.
Phase Ib results (48 patients, 16 weeks) showed up to 8.6% weight loss with no serious adverse events. A collaboration with Roche pairs it with CT-388 (a GIP/GLP-1 agonist), while Zealand also plans to combine it with other compounds. Evidence is currently limited to early-phase data with small sample sizes. Phase IIb results (ZUPREME-1) are expected in the first half of 2026 and will be critical for determining the compound's viability. The chemical stability enabling easy formulation with partner drugs is a genuine technical advantage over cagrilintide. Whether the amylin-alone mechanism can compete with multi-target approaches remains uncertain.
PeptideTrace tracks 5 registered clinical trials for Petrelintide sourced from ClinicalTrials.gov.
A Dose-Finding Study of Petrelintide With Enicepatide (RO7795068) in Adults With Obesity or Overweight
Investigating the Pharmacokinetics of Petrelintide Using Different Drug Product Concentrations
Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2)
Pharmacokinetics of Petrelintide Following Administration to Participants With Impaired Renal Function
Once-weekly Petrelintide Versus Placebo for Obesity or Overweight With Co-morbidities
Petrelintide (ZP8396) is a 36-amino-acid acylated amylin analog peptide developed by Zealand Pharma. The compound has a half-life of approximately 10 days, which is longer than cagrilintide's approximately 7 days. CAS number has not been publicly assigned. A critical differentiating feature is chemical stability at neutral pH, unlike cagrilintide which requires acidic pH, enabling co-formulation with other peptides. In March 2025, Roche entered an exclusive collaboration and licensing agreement with Zealand Pharma valued at $1.65 billion to co-develop and co-commercialize petrelintide.
Petrelintide acts as a potent balanced agonist of both amylin receptors (AMY1-3R) and the calcitonin receptor (CTR). The compound increases satiety signaling through area postrema and hypothalamic pathways and restores leptin sensitivity in preclinical models. Dose-proportional pharmacokinetics from 0.6 to 9.0 mg support predictable dose-response relationships in clinical development.
Phase 1b MAD Part 2 (NCT05613387; N=48; topline June 2024): maintenance doses achieved -4.8% (2.4 mg), -8.6% (4.8 mg), and -8.3% (9.0 mg) weight loss at 16 weeks versus -1.7% placebo. No serious adverse events were reported and no anti-drug antibodies were detected across any dose group. Phase 2b ZUPREME-1 (NCT06662539; 42-week treatment duration; enrollment completed March 2025) topline results are expected H1 2026. ZUPREME-2 for T2D was initiated in April 2025. The Roche collaboration ($1.65 billion) encompasses both petrelintide standalone development and a fixed-dose combination with CT-388.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version. Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway. The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
Timelines
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
