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Leanne M. Redman, Lilian de Jonge, Xiaobing Fang, Betsy Gamlin, David Recker, Frank L. Greenway, Steven R. Smith, Eric Ravussin, Lack of an Effect of a Novel β3-Adrenoceptor Agonist, TAK-677, on Energy Metabolism in Obese Individuals: A Double-Blind, Placebo-Controlled Randomized Study, The Journal of Clinical Endocrinology & Metabolism, Volume 92, Issue 2, 1 February 2007, Pages 527–531, https://doi.org/10.1210/jc.2006-1740
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Abstract
Objective: Our objective was to test the safety and metabolic effects of a novel β3-adrenoreceptor agonist (TAK-677) in humans.
Design, Setting, and Participants: Sixty-five obese (body mass index = 33.9 ± 2.1 kg/m2, mean ± se) men and women (31.4 ± 0.9 yr) participated in a double-blind placebo-controlled study at an institutional research center.
Intervention: Participants were randomized to 0.1 mg TAK-677 twice daily (BID) (n = 21), 0.5 mg TAK-677 BID (n = 22), or placebo BID (n = 22) for 29 d.
Outcomes: Drug safety, 24-h respiratory quotient (RQ), 24-h energy expenditure (EE), body composition, fat distribution, and fasting plasma concentration of substrates and hormones were assessed. An acute-response study was also conducted.
Results: The drug was well tolerated by all participants; however, heart rate was elevated (9 ± 2 beats per minute) with the 0.5-mg BID dose. After 28 d of treatment and when compared with placebo, there was no change in 24-h RQ with either 0.1-mg BID (P = 0.1) or 0.5-mg BID (P = 1.0) doses of TAK-677. However, TAK, 0.5 mg BID, resulted in a small increase in 24-h EE that was significantly different from placebo [change from baseline, 13 ± 17 (0.5 mg BID) vs.−39 ± 18 (placebo) kcal/d, P < 0.05]. Changes in weight, fat-free mass, and abdominal fat depots (visceral or sc) were not different between the three groups, nor were changes in fasting insulin, free fatty acid, or glucose concentrations.
Conclusion: TAK-677 has no effect on 24-h RQ or fat oxidation but does slightly increase 24-h EE at the highest dose (0.5 mg BID). The acute studies showed large interindividual variability in plasma concentrations of TAK-677 indicating some possible problems with bioavailability and therefore efficacy.
