Boehringer Ingelheim reports survodutide cut visceral and liver fat in two Phase 3 trials
Survodutide is not approved, but its Phase 3 results focus on fat stored around organs rather than total pounds, a distinction researchers say may matter for metabolic health.
On June 7, 2026, Boehringer Ingelheim reported that survodutide, an investigational glucagon/GLP-1 dual agonist, reduced visceral fat by up to 34% and liver fat by up to 63.1% over 76 weeks in adults with obesity or overweight, results the company said reflect a targeted reduction in metabolically harmful fat [1][2]. The findings from two Phase 3 trials were presented at the American Diabetes Association 2026 Scientific Sessions and published simultaneously in the New England Journal of Medicine and Nature Medicine [1][2].
What SYNCHRONIZE-1 found
The trial enrolled 725 adults with a BMI of 30 or higher, or 27 or higher with at least one obesity-related complication, and without type 2 diabetes, across 116 sites in 14 countries [2]. Participants received weekly injections of survodutide at 3.6 mg or 6.0 mg, or placebo, for 76 weeks alongside diet and activity counseling [1][2].
Under the efficacy estimand, which models full protocol adherence, average weight loss was 15.3% at 3.6 mg and 16.6% at 6.0 mg, compared with 3.2% for placebo (p<0.0001) [1][2]. Under the treatment-regimen estimand, which accounts for people who stopped treatment early, those figures were 12.2% and 13.0% versus 5.4% for placebo [2]. Overall, 28.5% of participants on the 6.0 mg dose lost at least 20% of body weight, compared with 6.6% on placebo [2].
In an MRI substudy of roughly 25 people per arm, visceral fat fell 34.0% at the 6.0 mg dose versus 11.8% with placebo, and liver fat fell 63.1% versus 24.5% [1][2]. Lean body volume declined 9.8%; the company said lean mass accounted for no more than 11.3% of the change in total tissue mass at the highest dose [1][2].
Lee Kaplan, director of the Obesity and Metabolism Institute and chair of the SYNCHRONIZE program executive committee, said the liver effect appeared earlier and more strongly than weight loss alone would explain. "What we're seeing is something that is specific to the treatment and is specific to the liver more than it is just an association with the amount of weight loss," he said [2].
The liver disease trial
SYNCHRONIZE-MASLD followed 218 adults with overweight or obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) with evidence of inflammation and/or fibrosis, with and without type 2 diabetes, for 48 weeks on survodutide 6.0 mg or placebo [1][2]. Under the efficacy estimand, 84.2% of treated participants had at least a 30% relative reduction in liver fat, compared with 24.3% on placebo (p<0.0001), and body weight fell by up to 12.2% versus 1.0% [1]. A secondary endpoint showed 61.0% reached liver fat normalization, defined as liver fat content below 5%, versus 5.7% on placebo [1][2]. Kaplan said a 30% liver fat reduction has been linked in the literature to improvement in MASH activity, and a 50% reduction to fibrosis improvement [2].
Safety and tolerability
The most common side effects were gastrointestinal — nausea, vomiting, diarrhea and constipation — mostly mild to moderate and usually during dose escalation [1]. The company reported that 19% of survodutide-treated participants in SYNCHRONIZE-1 stopped treatment because of GI side effects, versus 2.9% on placebo [1]. A separate report of the same trial gave 17.8% at 3.6 mg and 20.2% at 6.0 mg versus 2.9% on placebo [2]; the two accounts differ on the exact figure. No deaths were reported, and one ischemic stroke was confirmed in the placebo group; there were no confirmed cases of pancreatic cancer, thyroid cancer or acute pancreatitis, and a modest heart rate increase of 3.2 to 3.5 beats per minute was noted [2]. Investigators also reported that more than 16% of the placebo group used a prohibited GLP-1 medication during the trial, which likely inflated placebo weight loss [2].
Why it matters for patients
Survodutide has not been approved for any use, and the company states its efficacy and safety have not been established [1]. If it is eventually approved, it would join semaglutide and tirzepatide as another injectable option, but no head-to-head trial against either drug has been reported, so how these results compare is not known. The trial results describe average changes across groups rather than what any individual experienced. The focus on visceral and liver fat matters because excess fat around the abdomen and in the liver is linked to metabolic problems, and the company said up to three in four people living with obesity have MASLD, with about one in three of those progressing to the more serious MASH [1]. The GI side effects and the discontinuation rates are also relevant to anyone weighing tolerability, since roughly one in five treated participants stopped because of them [1][2]. Cost, insurance coverage and availability have not been disclosed.
What happens next
Boehringer said three Phase 3b studies will start later this year: SYNCHRONIZE-HERA in women's health, ELEVATE-LIVER on cardiac function and structure in people with MASLD or early MASH, and SYNCHRONIZE-START on real-world dose titration, including switching from GLP-1 receptor agonists [1]. The LIVERAGE and LIVERAGE-Cirrhosis trials in MASH with fibrosis are ongoing [1][2]. The FDA granted survodutide Fast Track designation in May 2021 and Breakthrough Therapy designation in September 2024 [1]. Survodutide is licensed to Boehringer Ingelheim from Zealand Pharma [1].
Sources
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