Acute metabolic and cardiovascular effects of mirabegron in healthy individuals

Aims To quantify acute energy expenditure, supraclavicular skin temperature and cardiovascular responses to four doses of the β3‐adrenoceptor agonist, mirabegron. Materials and methods A total of 17 individuals (11 men, six women) participated in this ascending‐dose study, receiving single 50‐, 100‐, 150‐ and 200‐mg doses of mirabegron on four separate days with 3 to 14 days wash‐out between each dose. All variables were measured each visit from baseline to 180 minutes post mirabegron treatment. To determine brown adipose tissue (BAT) thermogenic efficacy at each dose, energy expenditure and supraclavicular skin temperature were compared from baseline to 180 minutes post mirabegron treatment. To examine safety, changes in cardiovascular variables at 100, 150 and 200 mg were compared with the standard clinical dose of 50 mg. Results Energy expenditure significantly increased after the 100‐ (35.6 ± 5.4 kJ/h) and 200‐mg (35.6 ± 13.1 kJ/h) doses (P ≤ 0.05), and trended towards an increase after 150 mg (24.1 ± 13.6 kJ/h). Supraclavicular skin temperature increased after 50‐ (0.22 ± 0.1°C), 100‐ (0.30 ± 0.1°C) and 150‐mg mirabegron doses (0.29 ± 0.1°C; P ≤ 0.05). The change in systolic blood pressure was greater after 150‐ (7.1 ± 1.3 mm Hg) and 200‐mg doses (9.3 ± 1.9 mm Hg) than after the 50‐mg dose (2.2 ± 1.3 mm Hg; P ≤ 0.05). The change in heart rate was greater after 200 mg (9.0 ± 2.2 bpm) compared with 50 mg (2.9 ± 1.4 bpm; P ≤ 0.05). Conclusions A 100‐mg dose of mirabegron increases energy expenditure and supraclavicular skin temperature in a β3‐adrenoceptor‐specific manner, without the off‐target elevations in blood pressure or heart rate observed at higher doses.