Survodutide preferentially reduces metabolically harmful fat in obesity

Survodutide preferentially reduces metabolically harmful fat while largely preserving lean mass and muscle mass, according to new data from a body composition substudy of the phase III SYNCHRONIZE-1 trial involving adults with obesity without diabetes.

“Survodutide preferentially reduces visceral adipose tissue [VAT], liver fat and central fat, leading to a more metabolically favourable fat distribution,” said Professor Kirsi Pietiläinen of the University of Helskini, Finland, at EASD 2026. “Changes in body weight explain only part of the reductions in VAT and liver fat, suggesting that metabolic benefits extend beyond weight reduction.”

The body composition substudy included 75 patients (mean age, 47.7 years; female, 50.7 percent; mean BMI, 38.2 kg/m²; n=25 each in the survodutide 3.6 mg, survodutide 6 mg and placebo groups). Subcutaneous adipose tissue (SAT; including abdominal SAT [aSAT] and gluteofemoral SAT [gfSAT]), VAT (ie, abdominal VAT [aVAT]) and lean tissue compartments were measured by MRI from T9 to the knees at baseline and 76 weeks. [Pietiläinen K, EASD 2026; N Engl J Med 2026;395:776-787]

Favourable body composition changes
In the 75 patients, mean weight loss at 76 weeks was 16.7 and 18.4 percent with survodutide 3.6 and 6 mg, respectively, vs 6.9 percent with placebo. Survodutide was associated with relatively greater reductions in visceral and liver fat than in subcutaneous (SC) fat or lean mass.

Survodutide recipients lost up to 34 percent of VAT and up to 28 percent of SAT after treatment. “Liver fat reductions were astonishing, at 46 and 63.1 percent with survodutide 3.6 and 6 mg, respectively, vs 24.5 percent with placebo,” reported Pietiläinen. “In contrast, lean body volume did not change much with survodutide [-7.2 and -9.8 vs -2.9 percent].”

Preferential loss of abdominal & visceral fat
At baseline, survodutide recipients had 5.8 L of aVAT and 15.6 L of aSAT. “After survodutide treatment, the patients lost up to one-third of aVAT and about one-quarter of aSAT. That means about 2 L of aVAT and about 4 L of aSAT were lost,” said Pietiläinen.

SC fat showed larger reductions in the abdominal than gluteofemoral region after survodutide treatment.

“Adipose tissue loss with survodutide did not occur at the cost of lean body volume loss,” Pietiläinen pointed out. “In spite of greater weight loss, MRI-based lean loss ratio was not greater with survodutide vs placebo [11.1–11.3 vs 12.8 percent]. Muscle mass loss contributed to 8.9–10.2 vs 11.5 percent of total tissue mass loss.”

“Among survodutide recipients, weight loss explained 86 percent of variation of SAT loss, 50 percent of variation of VAT loss, and only 40 percent of variation of liver fat content reduction,” she continued. “This suggests weight loss–independent effects.”

High-quality weight loss
“These body composition outcomes at 76 weeks indicate high-quality weight loss with survodutide, with very meaningful weight loss and reductions in VAT and liver fat while preserving muscle mass,” said discussant Professor Andreas L Birkenfeld of University Hospital Tübigen, Germany.