Overactive bladder medication may stimulate brown fat metabolic benefits
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Women treated with the overactive bladder medication mirabegron experienced rises in brown adipose tissue metabolic activity as well as insulin sensitivity, resting energy expenditure and other metabolic factors after 4 weeks of treatment, according to findings published in the Journal of Clinical Investigation.
“Mirabegron increased brown fat activity, improved the lipoprotein profile, increased insulin sensitivity, and raised the levels of bile acids and adiponectin, both of which are associated with regulating aspects of metabolism,” Aaron M. Cypess, MD, PhD, MMSc, acting chief of the translational physiology section of the diabetes, endocrinology and obesity branch of the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH in Bethesda, Maryland, told Healio. “Any one of these changes would be important for our field. Seeing all of them is very encouraging.”
Cypess and colleagues used PET/CT to assess changes in brown adipose tissue metabolic activity, volume and maximum metabolic activity among 14 women (mean age, 27.5 years). Measurements were taken at baseline and after 4 weeks of a regimen of 100 mg of the beta-3 adrenergic receptor agonist mirabegron (Myrbetriq, Astellas Pharma). The researchers also assessed resting energy expenditure and levels of insulin, HDL cholesterol, adiponectin, apolipoprotein A-I, apolipoprotein E, bile acid and GIP, among other cardiometabolic factors.
The researchers observed greater median levels of brown adipose tissue metabolic activity (473 mL*g/mL vs. 195 mL*g/mL; P = .039), brown adipose tissue volume (149 mL vs. 72 mL; P = .036) and maximum metabolic activity (29 g/mL vs. 10 g/mL) at 4 weeks compared with baseline.
“Preclinical models show that chronic activation of brown fat leads to many metabolic benefits, including increased energy expenditure, improved cholesterol profile, higher insulin sensitivity and the release of brown adipokines that help other tissues consume fatty acids and glucose,” Cypess said. “Some of these effects are now beginning to be seen in humans.”
There was also a 10.7% rise in resting energy expenditure on the first day of treatment vs. baseline (P < .001) and a 5.8% rise at the beginning of the day in resting energy expenditure at 4 weeks vs. what was observed at the same time period at baseline (P = .01). In addition, the researchers observed a 37% rise in acute insulin response to glucose, a 36% rise in insulin sensitivity, a 34% rise in glucose effectiveness, a 35% rise in adiponectin, a 31% rise in GIP, a 12% rise in ApoA-1, an 8% rise in HDL cholesterol and a 7% rise in apolipoprotein E at 4 weeks vs. baseline.
“The research identifies several previously unknown clinical applications for a class of drugs that only recently became available to patients,” Cypess said. “Treatment with this class of medications could increase insulin sensitivity, providing an entirely new avenue through which to treat insulin resistance and type 2 diabetes. On a related point, this would be one of the only medications to raise HDL cholesterol, which could help treat dyslipidemia.”
There is still work to be done to determine the safety and effectiveness of this treatment.
“It is important to remember that the dose of mirabegron we studied was higher than what is considered safe by the FDA for long-term use,” Cypess said. “As such, we are still steps away from actual clinical applications, and future studies will need to look at larger groups of participants and different populations, such as older adults and people with obesity-related metabolic disease.” – by Phil Neuffer
For more information:
Aaron M. Cypess, MD, PhD, MMSc, can be reached at aaron.cypess@nih.gov.
Disclosure: Cypess reports no relevant financial disclosures.
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