Petrelintide helped people with overweight or obesity and type 2 diabetes lose up to 9.2% of their body weight over 28 weeks, while treatment withdrawals linked to gastrointestinal side effects remained close to placebo levels.
Zealand Pharma said its experimental amylin drug petrelintide helped people with overweight or obesity and type 2 diabetes lose as much as 9.2% of their body weight over 28 weeks, while keeping treatment withdrawals for stomach-related side effects unusually low. The company’s topline read-out from the Phase 2 ZUPREME-2 trial, announced on 7 October, suggests the once-weekly injection may offer a potentially better-tolerated route to weight management in a patient group where obesity and diabetes often reinforce each other.
The study enrolled 220 adults in the United States, all of whom were taking metformin, with or without an SGLT2 inhibitor, another class of diabetes medicine. Participants began with an average body mass index of 36.3 and a mean HbA1c of 8.0%, a measure of longer-term blood sugar control. Over the 28-week trial, volunteers received one of three doses of petrelintide or placebo, alongside advice to follow a reduced-calorie diet and increase physical activity.
According to the company’s figures, weight loss ranged from 7.4% to 9.2% in the petrelintide groups, compared with 2.0% in the placebo arm. Blood sugar also improved: HbA1c fell by up to 0.65% with petrelintide, while placebo was associated with a rise of 0.23%. Zealand said the results were broadly similar whether measured using an efficacy estimand, which assumes treatment is taken as intended, or a stricter regimen-based analysis.
The safety profile was the result that stood out most. Only 1.9% of people on petrelintide stopped treatment because of gastrointestinal side effects, compared with 1.7% in the placebo group. The company said most adverse events were mild and occurred while doses were being increased. David Kendall, chief medical officer at Zealand Pharma, said the findings “further support the potential of petrelintide in chronic weight management and, for the first time, demonstrate its promise as a standalone treatment for those living with overweight or obesity and type 2 diabetes.”
Petrelintide is designed to mimic amylin, a hormone released with insulin after eating. Zealand says the drug acts on amylin receptors and may help restore sensitivity to leptin, a hormone involved in satiety, so that people feel full sooner. Unlike GLP-1 drugs, which have dominated the obesity market, petrelintide works through a different biological pathway. The company has also engineered it for neutral pH stability, which could make it easier to combine with other peptide medicines.
The new data build on earlier work. Roche and Zealand previously reported positive results from the ZUPREME-1 trial in people without type 2 diabetes, and later published the full study in The Lancet Diabetes & Endocrinology. Roche said that trial showed weight loss of up to 10.7% at 42 weeks, with no vomiting and no treatment discontinuations from gastrointestinal side effects at the most effective dose. Taken together, the two studies suggest petrelintide may have the sort of tolerability profile that drug developers want if they hope patients will stay on treatment for years rather than weeks.
Even so, caution is warranted. The ZUPREME-2 figures are topline results from a company announcement, not a full peer-reviewed dataset. Zealand and Roche have already moved petrelintide into a Phase 3a programme spanning three studies, including trials in people with obesity, in those with type 2 diabetes and in patients with established cardiovascular disease. Roughly 7,000 participants are expected across the programme, which should do far more than 28 weeks of data to show whether the drug can deliver durable weight loss, sustained glycaemic benefit and long-term safety.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
