Petrelintide Shows Meaningful Weight Loss and High Tolerability in Phase 2 Obesity Trial

Petrelintide, a once-weekly injectable human amylin analog developed by Roche and Zealand Pharma, demonstrated up to 10.7% weight loss in adults with obesity or overweight without diabetes. According to results from the phase 2 ZUPREME-1 trial presented in New Orleans, the medication was well tolerated and improved several cardiovascular risk factors.

Why is Petrelintide different from GLP-1 therapies?

Petrelintide binds to different cell types than GLP-1 medications. W. Timothy Garvey, MD, an endocrinologist and professor at the University of Alabama (UAB) at Birmingham, noted that pulse rates tend to decrease with amylins. This contrasts with GLP-1s, which typically cause the pulse rate to increase.

Dr. Garvey suggested that the data indicates Petrelintide may be a better tolerated alternative to GLP-1 therapy. He believes the medication’s safety profile could make it particularly attractive for use in primary care settings.

Did You Know? Petrelintide’s ZUPREME-1 trial was conducted across 32 different sites located in the U.S., Poland, and Romania.

How did the ZUPREME-1 trial measure weight loss?

The phase 2, randomized, double-blind study enrolled 493 participants with a mean age of 47 and a mean BMI of 37 kg/m2. Participants received either a placebo or one of five different doses of Petrelintide, which were escalated every four weeks.

By week 42, those on the highest dose of Petrelintide saw weight reductions of up to 10.7%, compared to just 1.7% for the placebo group. The trial also recorded improvements in high-sensitivity C-reactive protein, triglycerides, and waist circumference.

Expert Insight: Samantha Carter notes that the significance of this trial lies in the trade-off between efficacy and tolerability. While the weight loss is described as modest compared to some other therapies, the “placebo-like” tolerability could expand access for patients who cannot handle the more intense side effects of higher-potency weight loss drugs.

What does the safety data reveal about tolerability?

Adverse events were reported by 70.8% of Petrelintide participants and 69.1% of the placebo group. Serious adverse events remained similar between the two, appearing in 3.5% of the treatment group and 3.7% of the placebo group.

ZUPREME-1: Petrelintide Reduces Obesity, Maintains Tolerability in Phase 2 Trial

Carel le Roux, MD, PhD, a professor at University College Dublin, described the tolerability as “almost looks placebo-like.” While nausea (19.6%) and constipation (6.9%) were more common in the Petrelintide group than the placebo group, most gastrointestinal events were mild.

What may happen next for amylin-based therapies?

Because many patients do not require a 25% to 30% reduction in weight, these results suggest Petrelintide could be positioned as a first-line medication for obesity. Its modest weight loss and safety profile may lead to wider adoption in primary care.

Future developments may depend on whether these outcomes are replicated in larger trials. A possible next step could involve further investigation into how this amylin analog performs over longer durations or in different patient populations.

Frequently Asked Questions

What is Petrelintide?
It is a long-acting human amylin analog being investigated as a once-weekly injectable therapy for adults with obesity or overweight who do not have diabetes.

How much weight loss was achieved in the trial?
At 42 weeks, the highest dose of Petrelintide resulted in weight loss of up to 10.7%, compared to 1.7% for the placebo group.

What were the most common side effects?
The most common reported side effects for those taking Petrelintide were nausea (19.6%) and constipation (6.9%).

Do you think a medication with modest weight loss is more appealing if it has fewer side effects?