Petrelintide from Zealand and Roche shows up to 9.2% weight loss in Phase 2 trial

Zealand Pharma and Roche reported on Oct. 7, 2026 that their experimental once-weekly drug petrelintide helped people who are overweight or obese and have type 2 diabetes lose 7.4% to 9.2% of their body weight after 28 weeks, depending on dose, compared with about 2% for placebo in a 220-patient Phase 2 trial ^[1][3].

The trial, called ZUPREME-2, met its main goal of statistically significant and clinically meaningful weight reduction compared with placebo ^[3]. Petrelintide is an amylin analog, meaning it copies amylin, a hormone the body releases along with insulin ^[1][3]. It is not a GLP-1 medicine like Ozempic and Wegovy (semaglutide) or Mounjaro and Zepbound (tirzepatide), and it is given as a weekly injection ^[1].

Blood sugar results drew a cooler response. Petrelintide lowered HbA1c, a measure of average blood sugar over roughly three months, by as much as 0.65 percentage points, while HbA1c rose 0.23% in the placebo group ^[1][3]. William Blair analysts said rival therapies have produced HbA1c reductions of 1.3% to 2.1%, and called a rise in the placebo arm "unusual" in obesity or type 2 diabetes studies ^[2][3]. The gap narrows once placebo is accounted for, because the control group got worse rather than holding steady ^[2].

Tolerability, which Zealand and Roche have made central to their pitch, looked close to placebo. About 1.9% of patients on petrelintide stopped treatment because of gastrointestinal side effects, compared with 1.7% of those on placebo ^[1][2][3]. Most GI side effects were mild and occurred while doses were being increased, Zealand said ^[1][3]. William Blair called the profile "largely comparable" to placebo and said the drug appeared to offer "an improved treatment experience" over approved weight loss drugs ^[2][3].

Weight loss got a mixed review. Analysts called it "intriguing" and said the 7.2% placebo-adjusted result matched what Eli Lilly reported in a Phase 2 trial of its amylin drug eloralintide, but said they were "disappointed" it was not larger ^[2][3]. Novo Nordisk's CagriSema showed deeper weight loss in Phase 3 testing, though it targets both amylin and GLP-1 ^[2].

William Blair said its current view is that petrelintide "will likely be used primarily in the maintenance setting, which demands a therapeutic intervention that exhibits placebo-like tolerability for chronic use" ^[2][3]. Roche licensed petrelintide from Zealand in March 2025 for $1.65 billion upfront, with the total deal value reaching up to $5.3 billion including milestones ^[1][3].

The readout followed a separate setback for Zealand. A week earlier, Zealand and partner Boehringer Ingelheim reported Phase 3 weight loss results for survodutide that fell short of expectations, and Zealand shares dropped more than 8% to 248.50 Danish kroner before drifting to about 240 after the petrelintide data ^[3].

Why it matters for patients

Petrelintide is not approved by the FDA and is not available outside clinical trials; the results reported so far come from a mid-stage study, not the large late-stage trials regulators generally require.

If it reaches the market, it would work differently from semaglutide and tirzepatide. Drugmakers are aiming amylin drugs at people who cannot tolerate GLP-1 medications or who stop them because of nausea and other gastrointestinal effects, though it has not been reported whether any ZUPREME-2 participant had taken a GLP-1 before.

The blood sugar finding matters for people with type 2 diabetes, because HbA1c control is a main reason they take medicine. Whether the 0.65 percentage point drop reflects a real weakness of the drug or the design of this one trial has not been established. All comparisons reported so far are across separate trials, not head-to-head studies. Weight loss in people with type 2 diabetes is typically lower than in people without it, which analysts noted ^[2][3].

What happens next

Zealand and Roche have begun a Phase 3 program that Reuters said will enroll about 7,000 people, including people with and without type 2 diabetes and people with established cardiovascular disease ^[1]. BioSpace reported it as three trials: ZUPREME-3 in people with obesity or overweight without type 2 diabetes, ZUPREME-4 in people with type 2 diabetes, and ZUPREME-5 in people with cardiovascular disease ^[3]. ZUPREME-4 is listed as recruiting 600 people with overweight or obesity and type 2 diabetes ^[2]. William Blair said no meaningful catalysts are expected within the next year that could change how investors view petrelintide ^[3]. No completion dates or regulatory filing timelines have been disclosed.