Zealand Pharma and its development partner Roche announced on September 22, 2026 that they have begun a registrational Phase 3 program, called ZUPREME, for petrelintide, an investigational amylin analog for chronic weight management. The move pushes petrelintide, one of the most closely watched candidates in the crowded obesity-drug pipeline, into the final stage of testing before a potential marketing application.
What Petrelintide Is
Petrelintide is a long-acting amylin analog designed for once-weekly subcutaneous injection. Amylin is a hormone the pancreas releases alongside insulin, and drugs that activate amylin receptors are thought to promote fullness and help restore sensitivity to leptin, a separate hormone involved in appetite regulation. That mechanism is distinct from GLP-1 receptor agonists like semaglutide and tirzepatide, though amylin analogs are frequently studied either alone or in combination with GLP-1 drugs. Petrelintide has not been approved by the FDA or any other regulator; it remains an investigational compound.
Inside the ZUPREME Program
The Phase 3 program consists of three separate randomized, double-blind, placebo-controlled trials enrolling a combined total of roughly 7,000 participants:
ZUPREME-3 will enroll about 3,900 participants with overweight or obesity and at least one weight-related health condition, excluding type 2 diabetes. ZUPREME-4 will enroll roughly 600 participants who have overweight or obesity along with type 2 diabetes. ZUPREME-5, the largest and longest of the three, will enroll about 2,500 participants with overweight or obesity and established cardiovascular disease, with a treatment period that can extend up to three years to capture cardiovascular outcome data.
All three trials compare once-weekly petrelintide against placebo. ZUPREME-3 and ZUPREME-4 include a 12-week dose-escalation period followed by a maintenance phase running through week 64, with an optional open-label extension after that. ZUPREME-5 is structured around a longer event-driven maintenance phase given its cardiovascular focus.
What Earlier Data Showed
The companies point to Phase 2 results as the basis for advancing to this scale of testing, describing "double-digit weight loss with a tolerability profile largely comparable to placebo." Those figures come from an earlier, smaller trial population; the Phase 3 program exists specifically to confirm whether that effect and safety profile hold up across a much larger and more diverse group of patients, including people with diabetes and existing heart disease who were not the focus of earlier testing.
The Roche Partnership
Zealand Pharma and Roche have collaborated on petrelintide's development since a 2025 licensing agreement under which Roche took on co-development and eventual co-commercialization rights. Roche's involvement gives the program access to larger-scale trial infrastructure, which is reflected in the size of the newly launched studies.
Regulatory Status and What Comes Next
Petrelintide has no FDA approval and is not available for prescription or compounding use in the United States. Phase 3 initiation is a meaningful milestone, but it is still an early step in a process that, based on the trial designs, will run for years: the maintenance phases alone extend to week 64 or beyond, and cardiovascular outcome data from ZUPREME-5 will take considerably longer to mature. Regulatory submission would only follow successful completion of these trials.
Anyone currently being treated for obesity, diabetes, or cardiovascular disease with an approved medication should not view an investigational drug's Phase 3 launch as a reason to change their current treatment plan, and should direct any questions about their own care to their physician.