A National Institutes of Health study found that chronic treatment with mirabegron, a drug approved to treat overactive bladder, activated brown fat in a small group of healthy women and had several other beneficial metabolic effects. Brown fat, or brown adipose tissue, is a form of fat that burns calories to generate heat. The research, led by Aaron Cypess, MD, PhD, at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was published on January 21 in the Journal of Clinical Investigation.

Fourteen women aged 18-40 of diverse ethnicities participated in the study at the NIH Clinical Center’s Metabolic Clinical Research Unit. For 4 weeks, each participant received daily doses of 100 mg of mirabegron, an amount exceeding the 50 mg maximum dosage approved by the US Food and Drug Administration.

At 4 weeks, the participants’ brown fat activity had more than doubled since the first day, though their body weight and body mass stayed the same. Other changes included:

• Increased resting energy expenditure
• Higher levels of HDL (high-density lipoprotein) cholesterol—often referred to as “good” cholesterol—and bile acids, which help digest fats and regulate cholesterol
• Improved processing and regulation of blood glucose (blood sugar) 

Dr. Cypess and his colleagues previously found that a single dose of mirabegron increased brown fat activity and energy expenditure in healthy men, but the changes to HDL cholesterol, bile acids, and glucose processing were not seen. Of note, all these studies used dosages higher than currently approved by the FDA, as these doses were better able to show the drug’s potential metabolic benefits. However, the higher doses of mirabegron are linked to cardiovascular risk. Both male and female study participants did experience increased heart rates and blood pressure, which returned to normal after mirabegron treatment ended. 

More research is needed to determine if mirabegron has metabolic benefits in a wider range of people, including older adults and people with obesity, and if similar drugs might produce these benefits without increasing cardiovascular risk. The present study, however, brings scientists closer to identifying a safe, effective way to activate brown fat and potentially treat metabolic disease.