Tirzepatide seemed to activate brown adipose tissue (BAT) in women with obesity, possibly yielding weight-loss benefits, a new study suggested. 

Research over the past two decades has shown that BAT activity is closely linked to cardiometabolic health, Rok Herman, MD, University Medical Centre Ljubljana in Ljubljana, Slovenia, told Medscape Medical News. “This is particularly relevant in obesity, where brown fat activity is markedly reduced, while growing evidence suggests that its activation may improve metabolic parameters.”

“In addition, the field has increasingly recognized that beige adipocytes, which can emerge within white adipose tissue under certain stimuli, may represent another important component of human thermogenic adipose tissue,” he said.

Taken together, the findings prompted Herman and colleagues to ask whether new obesity medications could activate thermogenic fat tissue.

“One of the more unexpected findings [from our study] was a signal consistent with activation or recruitment of BAT following tirzepatide treatment, despite substantial weight loss,” he said. “This is notable because weight loss is typically accompanied by adaptive reductions in energy expenditure. We were also encouraged by the consistency of the signal across the different imaging modalities employed in the study.”

Herman presented the study on June 15 at ENDO 2026: The Endocrine Society Annual Meeting in Chicago.

‘Preliminary Observations’

Researchers conducted a 24-week trial in 34 women with obesity (median age, 39.5 years; median BMI, 36.9), randomized in a 1:1 ratio to once weekly subcutaneous tirzepatide (mean dose, 8.8 mg) or placebo.

They assessed BAT before and after the intervention using cold-stimulated [18F]FDG PET/CT with personalized cooling protocols, where the temperature was adjusted to each participant’s predetermined shivering threshold.

BAT also was assessed by thermoneutral MRI, and resting energy expenditure was measured by indirect calorimetry.

The researchers also performed exploratory quantitative PCR (qPCR) analyses of thermogenic and mitochondrial genes in adipose tissue biopsies in a subset of tirzepatide-treated participants with BAT activation.

Overall, Herman said, “We found that tirzepatide significantly increased BAT activity and volume, and it also showed potential signs of converting white subcutaneous fat into more metabolically active ‘beige’ fat.”

Specifically, tirzepatide increased [18F]FDG PET/CT-detectable BAT activity in a significant proportion of participants (41.2% at baseline vs 64.7% after intervention), whereas no change was seen in the placebo group.

Cold-stimulated BAT metabolic activity and volume also increased significantly in the tirzepatide group, including mean standardized uptake value (SUVmean), SUVpeak, total metabolically active BAT volume (TMBATV), and total BAT activity. Absolute changes in SUVmean, TMBATV, and TMBAT activity were significantly greater than placebo.

Furthermore, MRI-based assessment of supraclavicular BAT fat fraction reduction demonstrated changes consistent with [18F]FDG PET/CT-measured BAT activation in the tirzepatide group.

“The concordant findings across cold-stimulated FDG PET/CT, thermoneutral MRI, and cold-stimulated infrared thermography are noteworthy,” Herman said. “In particular, infrared thermography during cold exposure showed promise as a noninvasive method to assess brown fat activity. This could be valuable for future research, as other methods are costly, involve radiation exposure, and are less practical for repeated or large-scale assessments.”

In addition, median weight loss with tirzepatide was 13.5%, and changes in body weight were not associated with changes in any PET/CT BAT parameters.

Resting energy expenditure did not differ significantly between groups; however, a numerically greater decline was observed in tirzepatide-treated participants without BAT activation. The exploratory qPCR analysis in the subset of tirzepatide-treated participants with BAT activation showed increased expression of selected thermogenic and mitochondrial genes.

“Our findings add to growing evidence that BAT is a functionally active and potentially modifiable contributor to metabolic health in adults,” Herman said. “Although these observations remain preliminary and are not yet ready for clinical translation, they highlight the importance of continued research into thermogenic adipose tissue and its regulation.”

‘Exciting Early Insight’

“The results are plausible and consistent with current biology,” said Yu-Hua Tseng, PhD, senior investigator in the Section on Integrative Physiology and Metabolism at the Joslin Diabetes Center, Boston, who was not involved in the study.

“The study is small and limited to middle-aged women with obesity, so it is unclear whether the findings generalize to men, other age groups, or people with different body weights,” she told Medscape Medical News. Participants’ diabetes status is also unknown, “making it difficult to link brown fat activation to changes in glucose control or insulin sensitivity.”

“Finally,” she continued, “the adipose depot used for gene-expression analyses is not specified; if the biopsies were from abdominal white fat rather than a classic brown fat region, the observed increase in thermogenic genes could indicate ‘browning’ of white fat, which would be particularly exciting and should be clarified.”

“Brown fat not only burns calories but also releases signaling molecules that influence other organs,” she noted. “Prior work from my lab suggests these factors contribute to its metabolic benefits.”

For now, she added, the study “should be viewed as an exciting, early mechanistic insight rather than a reason to change prescribing decisions, but it may help explain some of tirzepatide’s metabolic benefits and point to new therapeutic possibilities targeting brown fat.”

André C. Carpentier, MD, professor and Canada Research Chair in Molecular Imaging of Diabetes, University of Sherbrooke, Sherbrooke, Quebec, Canada, also commented on the study. The findings bring “significant new information,” he said, and “are concordant with improved BAT glucose uptake (or reduction) with modulation of insulin sensitivity/caloric balance previously demonstrated in humans.”

“The main caveat is that BAT glucose uptake is just that and does not necessarily mean that BAT thermogenesis is increased,” he noted. “Future studies need to assess BAT thermogenesis using specific methods to do so, such as oxygen-15 or 11C-acetate PET.”

Herman had no disclosures to report. Tseng reported serving as a consultant to Paratus Sciences and Sofinnova Partners. Carpentier reported serving on advisory panels for Eli Lilly, Novo Nordisk, and Merck; and being a principal investigator in Sherbrooke for the TREASURE-CKD multicenter international trial.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.