As the American Diabetes Association 2026 Scientific Sessions kicked off in New Orleans over the weekend, Zealand Pharma and its partner Roche helped get the show rolling with a deep dive into their amylin analog petrelintide.
In new data from the midphase ZUPREME-1 trial presented Friday, Zealand provided a closer look at the trial win it first unveiled in March, stressing the tolerability edge that the Danish company and its Big Pharma partner claim petrelintide—with its distinct mechanism of action from other anti-obesity therapies—could deliver.
Three months ago, the company revealed that the drug helped patients log a 10.7% mean drop in weight from baseline through 42 weeks. The study also hit its primary endpoint of 28-week weight loss—although that data has yet to be shared.
In the dose-finding trial, which pitted placebo against five doses of petrelintide, between 88% to 98% of patients on the study drug reached their target maintenance dose during an up to 16-week dose escalation period, Zealand said Friday.
Adding to the drug’s tolerability profile, meanwhile, more than 75% of gastrointestinal adverse events logged on petrelintide were “mild,” according to a Zealand abstract presented at ADA. Nausea was the most common of those side effects, cropping up in 19.6% of patients on petrelintide versus 6.2% of participants in the placebo cohort, and rates of vomiting actually occurred less in the study drug arm versus the control cohort, Zealand pointed out.
Rates of diarrhea and constipation were “similarly low” for both Zealand and Roche’s amylin analog, according to a June 5 release.
Overall, the weight loss data for petrelintide reported earlier this year were “meaningful,” and the “tolerability profile is really quite remarkable,” Manu Chakravarthy, M.D., Ph.D., global head of cardiovascular, renal and metabolism product development at Roche, told Fierce in an interview on the conference sidelines.
“You’re getting double-digit weight loss—very clinically meaningful—and you get this placebo-like tolerability, which is not to be underappreciated,” Chakravarthy explained. Tolerability “is and remains the number one unmet need” when looking at obesity medications, he added, because it impacts adherence and in turn the ability of those drugs to help patients to their full potential.
While Zealand revealed earlier this year that petrelintide was tied to a 4.8% discontinuation rate due to adverse events overall, the company clarified Friday that only 1.5% of participants stopped use of petrelintide due to gastrointestinal side effects, which are a hallmark of other hormone receptor agonist-based obesity meds and remain one of the top factors under consideration as companies develop the next generation of metabolic treatments.
Meanwhile, Zealand and Roche are also padding the case for petrelintide by highlighting the drug’s association with meaningful improvements in a number of cardiovascular risk factors, including waist circumference, blood pressure, lipids and high-sensitivity C-reactive protein (hsCRP).
Specifically, petrelintide helped patients chart reductions ranging from 7.9 to 10.8 centimeters for waist circumference, versus 4.3 centimeters on placebo, plus reductions of 17% to 41% for hsCRP, as compared to an average 6% reduction with placebo. Moreover, petrelintide helped patients achieve a 12% to 21% triglyercide reduction, compared to 9% in the trial’s control cohort, Zealand said.
In the topline data issued earlier this year, Zealand noted that petrelintide helped patients achieve statistically significant reductions in weight after 28 weeks but did not provide detailed data on the med’s performance at that time, noting instead that patients sustained up to 10.7% mean weight loss at week 42 of the study. By comparison, patients in the trial’s placebo cohort logged an average weight reduction of 1.7%.
Fierce was unable to get confirmation of when the specific 28-week data would see the light of day. In response, a Roche spokesperson explained that while “weight loss curves across 28 weeks and 42 weeks” had been presented at ADA, the company plans to share more data at the trial at a separate upcoming medical conference.
“The reason why we did the 28-week [trial] was to kind of get an early view into what we are looking at—is there a trajectory here, is there enough of a magnitude that can give us confidence to move into phase 3?” Chakravarthy said of the trial’s primary endpoint.
The results are promising enough that Roche and Zealand are planning to launch a phase 3 program for petrelintide in the second half of 2026, he added.
The detailed side effect figures reinforce Zealand’s assertion earlier this year that petrelintide’s tolerability could improve adherence to obesity meds, albeit at a magnitude of weight loss that more than a few analysts found underwhelming in March.
While the scope of the average weight loss logged on petrelintide appears to lag that offered up by incretin meds like Novo Nordisk's Wegovy and Eli Lilly's Zepbound, mean weight loss alone fails to capture the full story, Chakravarthy argued. Moreover, as a new generation of obesity medications advance through the clinic, tailoring different therapeutic options to meet patients where they are will be paramount, and for some, more “gentle weight loss,” coupled with an improved tolerability profile, could make petrelintide an attractive option, according to Chakravarthy.
The drug might also appeal to those starting on an anti-obesity medication for the first time, for the same reasons above, he explained.
Unlike the GLP-1-based incretin meds currently on offer for obesity, diabetes and related conditions, petrelintide acts on the amylin receptors in the brain, with Zealand noting that activation of the receptor has been shown to reduce body weight by restoring sensitivity to the satiety hormone leptin, and in turn helping patients feel full faster.
Still, Chakravarthy acknowledged the heterogeneity of obesity, noting that the company is trialing other candidates, such as the dual GIP/GLP-1 agonist enicepatide, for patients who need a higher degree of weight loss. Further, Roche and Zealand are additionally looking at a combination of the two assets, with plans to kick off a phase 2 study of the pairing in the back half of 2026.
“The biology of amylins and GLP-1s are complementary to each other,” Chakravarthy said.
As part of Roche's efforts to hone its wide-ranging obesity ambitions, the company last year floated $1.65 billion upfront to codevelop and commercialize petrelintide.
At the company’s Pharma Day in September 2025, Roche’s pharmaceuticals CEO Teresa Graham announced the Swiss company had set its sights on becoming a “top three” obesity drugmaker, noting that the aim is to become a “strong entrant” in the space before the end of the decade.
At the same event, Chakravarthy told Fierce that the company needed a range of assets, rather than a singular metabolic cash cow, to address the complexity and heterogeneity of the obesity market.