Boehringer Ingelheim spent the weekend pointing to survodutide's “targeted” weight loss, but the latest data couldn’t shake off concerns about the obesity drug’s tolerability.
The deep dive into survodutide’s performance—presented Sunday at the American Diabetes Association 2026 Scientific Sessions in New Orleans—reaffirmed that survodutide was linked to an average weight decrease of 16.6% on the efficacy estimand, versus 3.2% among patients in the phase 3 Synchronize-1 trial’s placebo cohort.
By that metric, the average weight loss on servodutide is in the ballpark of the originally approved highest dose of Novo Nordisk’s Wegovy, although it falls short of Eli Lilly’s Zepbound.
New to the table were detailed glimpses into the dual agonist’s ability to cut specific types of weight thought to have the greatest impact on overall metabolic health, while also potentially better preserving lean mass than other comparable therapies.
Namely, a sub-study of Synchronize-1 that looked at patients who provided MRI measurements at baseline and the end of the trial showed a relative reduction of up to 34% visceral fat—a term for the fat surrounding the organs—compared to 12% among patients on placebo. Meanwhile, “no more than 10.8%” of change in total tissue mass at the highest survodutide dose suggested that weight loss was “primarily driven by reductions in fat mass,” Boehringer argued in a June 7 release.
With survodutide, the German drugmaker believes it has the potential to address the high unmet need of “targeted weight loss,” Vani Manja, head of Boehringer Ingelheim’s obesity and liver health therapeutic area, told Fierce in an interview ahead of the conference.
“We want to be playing a role in this shift towards long-term metabolic health, beyond just weight loss and obesity,” she explained. “What you’ve seen at the high level from the topline results, and what we’re presenting at ADA, truly build on that meaningful weight loss alongside data on liver fat, visceral fat, and data on lean mass … that help us better understand the quality of weight loss.”
On the lean mass ratio, which represents lean tissue lost versus the total tissue mass patients lost, Manja noted that the 10.8% figure in the trial suggests that “the majority of the weight loss observed was driven by fat loss.” Loss of muscle mass has remained an issue of concern around incretin medicines for chronic weight loss.
“These effects are particularly relevant when we talk about metabolic disease, solving metabolic disease and delivering long-term metabolic health,” Manja said. “The number on the scale is only part of the story, and we look now to understand the rest of the story and make an impact there.”
While the weight loss figures tracked with previous readouts, tolerability remained a sore spot for survodutide. After topline results from midphase trial several years back revealed that nearly a quarter of patients discontinued the treatment, the CEO of Zealand Pharma—which licensed survodutide to Boehringer—suggested earlier this year that flexible titration and antiemetic drugs could help control side effects in the phase 3 study presented at ADA.
But in detailed results from Synchronize-1 published in The New England Journal of Medicine on Sunday, nearly 24% of patients on the 3.6 mg dose of survodutide and nearly 25% of patients on the higher 6 mg dose discontinued treatment due to an adverse event (AE), versus around 5.4% of patients on placebo.
Framed another way in Boehringer’s press release, 19% of patients discontinued treatment with servodutide due to gastrointestinal side effects specifically in Synchronize-1, compared to 2.9% of patients in the placebo group.
Either way, the discontinuation rate does not appear to track favorably with those seen in pivotal trials of Lilly and Novo’s incretin meds for obesity. Wegovy and Zepbound's pivotal trials saw discontinuations due to AEs range from 2.6% to 7.1% depending on the dose.
“The GLPs have all shown some degree of gastrointestinal symptoms, and I can tell you that our AE profile is consistent with that,” Neerja Balachander, Ph.D., VP of U.S. clinical development medical affairs and therapeutic area head for cardiorenal metabolic at Boehringer, told Fierce in a separate interview ahead of the conference.
To a certain extent, difficulties with gastrointestinal side effects could be ameliorated as health systems figure out how to better support patients taking incretin meds for obesity, Balachander argued.
“I do think that it is important for patients to know how to use it, because again, there’s a lot of interest in utilization,” she said. “But I do not think that the healthcare systems yet know how to slowly help these patients with these AEs, and I think that’s something that we at Boehringer are really committed to doing.”
A deepening understanding at all levels that obesity is a chronic disease—and not just something for which a person pursues aesthetic weight loss—could also go a long way toward better improving adherence and managing side effects, Balachander added. Additionally, patients need to be proactive when dealing with side effects, “so that you can either up-titrate or down-titrate these drugs,” she said.
More remains to be done to educate “the healthcare community, as well as the patients, that these are serious interventions,” she explained. “They give you great effect, but there are some rules that you have to follow,” she said of managing side effect burden through improvements to diet and other factors.
Liver differentiation
One area where Boehringer still hopes to have an edge is survodutide's effect on the liver. A pre-specified analysis of Synchronize-1 found patients on survodutide charted liver fat reductions of up to 63.1%, compared to 25% in the study’s control cohort.
The pharma also used ADA to disclose data on its phase 3 Synchronize-MASLD trial, which assessed the dual agonist in adults with obesity or who were overweight who had metabolic dysfunction-associated steatotic liver disease (MASLD) with evidence of inflammation and or fibrosis. That study recruited patients both with and without type 2 diabetes.
Boehringer noted that the trial met the mark, with up to 84.2% of patients on survodutide achieving at least a 30% relative liver fat reduction on the efficacy estimand—representing patients who took their treatment regimen as instructed—versus 24.3% in the placebo arm. On a co-primary endpoint, survodutide was linked to a 12.2% relative reduction in body weight, once more on the efficacy estimand, versus 1% in the control cohort.
MASLD is a condition in which excess fat builds up in the liver. Upwards of 75% of people with obesity will develop MASLD, according to Boehringer, and for one in three the condition can advance to the more serious stage known as metabolic dysfunction-associated steatohepatitis (MASH).
Back in April, analysts at William Blair suggested that with little in the standard weight loss data to make Boehringer's drug stand out from approved options, survodutide’s “potential differentiation could derive from its liver-related benefit.”