Amylin Drug Petrelintide Cut Weight Up to 9.2% in Diabetes Trial

This article is based on that report. The paper itself was not reviewed, and the figures come from a company announcement.

According to Longevity.Technology, Zealand Pharma announced topline results on 7 October from ZUPREME-2, a Phase 2 trial. It enrolled 220 people in the United States who had overweight or obesity and type 2 diabetes. All were taking metformin, with or without a type of diabetes drug called an SGLT2 inhibitor. On average, they started with a BMI of 36.3 and an HbA1c of 8.0%. HbA1c is a blood test that reflects average blood sugar over recent months.

Participants got a once-weekly injection at one of three doses, or a placebo, for 28 weeks, the report says. Everyone also followed a reduced-calorie diet and was encouraged to be more active.

By week 28, weight loss reached up to 9.2% of starting body weight, with the three dose groups between 7.4% and 9.2%. Placebo came in at 2.0%, according to the report. The 9.2% figure counts results as if everyone took the drug as planned. The company says results were largely consistent under a stricter method that includes people regardless of their dosing.

HbA1c fell by up to 0.65% on petrelintide and rose by 0.23% on placebo, per the report. After subtracting the placebo effect, the company reports reductions of 0.61% to 0.88% across the dose groups.

The tolerability figure is the one that stood out. Longevity.Technology reports that 1.9% of people on petrelintide stopped because of stomach-related side effects, versus 1.7% on placebo. The most common side effects were stomach-related. The report says the vast majority were mild and appeared while doses were being raised. No unexpected safety signals appeared, according to the company.

Petrelintide works differently from the widely known GLP-1 drugs. It is a long-acting version of amylin, a hormone the pancreas releases alongside insulin when people eat. According to the company, activating amylin receptors can restore sensitivity to leptin, a hormone involved in fullness, so people feel full sooner.

This adds to an earlier Arising report on Eli Lilly's daily pill Foundayo (orforglipron), which a European drug committee recommended for approval. That story covered a GLP-1 tablet. This one covers a different hormone target, and the two are separate products and trials.

The caution is real. These are topline numbers from a company press release, and 28 weeks says little about how long people can stay on treatment or how well benefits last. The small gap in dropouts is encouraging, but it does not show that petrelintide is better tolerated than other drugs, because it was not compared with them.

According to the report, Zealand and Roche have started a Phase 3a program of three trials, ZUPREME-3, -4 and -5, with roughly 7,000 participants expected. They cover people without type 2 diabetes, people with it, and people with established cardiovascular disease. Full ZUPREME-2 results are due at an upcoming scientific conference, and those details, along with the Phase 3 data, will show whether the early signal holds.

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