Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial.

Abstract

To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes (N = 335, aged 18-65 years, BMI ≥30 to <50 kg/m2 or BMI ≥27 to <50 kg/m2 with hypertension and/or dyslipidemia). Participants were randomized (1:1:1:1) to receive PBO, CANA 300 mg, PHEN 15 mg, or coadministration of CANA 300 mg and PHEN 15 mg (CANA/PHEN) orally once daily. The primary end point was percent change in body weight from baseline to week 26; key secondary end points were the proportion of participants achieving weight loss ≥5% and change from baseline in systolic blood pressure. CANA/PHEN provided statistically superior weight loss from baseline versus PBO at week 26 (least squares mean difference -6.9% [95% CI -8.6 to -5.2]; P < 0.001). CANA/PHEN also provided statistically superior achievement of weight loss ≥5% and reduction in systolic blood pressure compared with PBO. CANA/PHEN was generally well tolerated, with a safety and tolerability profile consistent with that of the individual components. CANA/PHEN produced meaningful reductions in body weight and was generally well tolerated in individuals who were overweight or obese without type 2 diabetes. Further studies are warranted to evaluate potential use of this combination for long-term weight management.