Zealand Pharma's experimental obesity drug petrelintide cut body weight by up to 9.2% in a mid-stage trial of patients with type 2 diabetes, the Danish biotech announced on Wednesday — a result analysts called "intriguing" even as they balked at the drug's weaker-than-expected effect on blood sugar. The Phase 2 ZUPREME-2 trial met its primary endpoint in 220 patients, but it was the second Zealand readout in a week to disappoint investors.
What the ZUPREME-2 trial showed
The trial tested once-weekly subcutaneous injections of petrelintide, a long-acting amylin analog being developed with Roche, against placebo in 220 people with overweight or obesity and type 2 diabetes (mean baseline BMI of 36.3 and mean baseline HbA1c of 8.0%). Participants lost between 7.4% and 9.2% of body weight after 28 weeks, depending on the dose, versus 2% with placebo. The trial met its primary endpoint of statistically significant and clinically meaningful weight reduction.
William Blair analysts said the result was broadly in line with Eli Lilly's rival amylin drug eloralintide and the approved GLP-1 Zepbound, and ahead of Novo Nordisk's Wegovy, which managed 4–5% weight loss at the same time point. Still, the firm said it was "disappointed" the drug did not deliver greater weight loss.
Blood sugar: the weak spot
Petrelintide reduced HbA1c, a key marker of average blood sugar, by up to 0.65%, while placebo participants saw a 0.23% increase. Rival therapies achieved reductions of 1.3%–2.1%, and William Blair flagged the rise in the placebo arm as "unusual" for obesity and diabetes studies. On the combined ZUPREME-1 and ZUPREME-2 results, the analysts concluded petrelintide showed "highly encouraging tolerability, though the magnitude of weight loss (along with HbA1c reduction in ZUPREME-2) disappointed."
Tolerability is the selling point
The bright spot was safety: gastrointestinal side effects were mostly mild and clustered during dose escalation, and only 1.9% of patients on petrelintide discontinued because of them, versus 1.7% on placebo — suggesting an "improved treatment experience" over drugs like Wegovy and Zepbound. Analysts see petrelintide fitting best as a long-term maintenance therapy and in the overweight (rather than obese) segment, where gentle, well-tolerated weight loss could carry real value.
Zealand and Roche have already kicked off a Phase 3a program — ZUPREME-3, ZUPREME-4 and ZUPREME-5 — enrolling 7,000 patients with obesity or overweight without type 2 diabetes, with type 2 diabetes, and with cardiovascular disease respectively. Roche licensed petrelintide in March 2025 in a deal worth up to $5.3 billion, including $1.65 billion upfront.
A rough week for Zealand
The readout came days after disappointing Phase 3 results for survodutide, Zealand's GLP-1/glucagon drug developed with Boehringer Ingelheim, which hit up to 13.1% weight loss at 76 weeks but still underperformed expectations. Zealand shares fell more than 8% to $248.50 on the Danish market and drifted toward $240 after the petrelintide data. With no major catalysts expected within the next year, analysts now see a "balanced risk/reward profile" — supported by a strong cash position, a buyback program, and a deep pipeline.
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