In adults with overweight or obesity but without diabetes, coadministration of canagliflozin and phentermine conferred greater weight loss at 26 weeks vs. monotherapy with either agent or a placebo, according to findings from a randomized controlled trial.
“It has become apparent with the current obesity drugs on the market that one approach does not fit all by any means,” Priscilla Hollander, MD, PhD, of the Baylor Endocrine Center at Baylor University Medical Center, told Endocrine Today. “This combination therapy may have a better effect because it hits at least two targets in the multifactor causes of obesity.”
Hollander and colleagues analyzed data from 335 adults without diabetes and BMI between 30 kg/m² and 50 kg/m² or between 27 kg/m² and 50 kg/m² with hypertension or dyslipidemia (mean age, 46 years; mean BMI, 37.3 kg/m²). Between September 2014 and June 2015, researchers randomly assigned patients to four groups for 26 weeks: 300-mg canagliflozin (Invokana, Janssen) monotherapy daily (n = 84); 15-mg phentermine daily (n = 85); combination therapy (n = 83) or placebo (n = 82). Primary endpoint was percent change in body weight from baseline to week 26; secondary endpoints were the proportion of patients achieving at least 5% weight loss and change in systolic blood pressure.
Patients assigned combination therapy saw the greatest percent change in body weight during the study (least-squares mean difference, –7.5%), followed by patients assigned phentermine (least squares mean difference, –4.1%), canagliflozin (least-squares mean difference, –1.9%) and placebo (least-squares mean difference, –0.6%). Patients assigned combination therapy experienced greater percent weight loss vs. placebo (difference of –6.9%; P < .001) and a greater absolute reduction in body weight vs. placebo (difference of –6.7 kg; P < .001). The separation in treatment effect on body weight was observed as early as week 6, according to the researchers, and weight loss with combination therapy continued through study end with no apparent plateau.
A greater proportion of patients also achieved weight loss of at least 5% with combination therapy vs. placebo at week 26 (66.7% vs. 17.5%; P < .001); 34.9% of patients assigned combination therapy saw weight loss of at least 10%.
Least-squares mean reductions in systolic BP were –6.9 mm Hg for combination therapy, –1.4 mm Hg for phentermine, –3.1 mm Hg for canagliflozin and –2.7 mm Hg for placebo. Consistent with known effects of phentermine therapy, patients in both the phentermine monotherapy and combination therapy groups experienced increased pulse rate vs. placebo (4.1 bpm and 3.5 bpm vs. –0.7 bpm, respectively). Combination therapy was generally well tolerated, with a safety profile consistent with the individual therapies, according to the researchers.
“We know obesity is an epidemic, and if patients can lose even a modest amount of weight, it can very favorably affect and minimize the comorbid states of obesity, certainly diabetes,” Hollander said. “We need further trials in different and more extensive populations to show the true effectiveness and safety of this combination therapy.” – by Regina Schaffer
Disclosure: Janssen Research & Development supported this study. Hollander reports serving on advisory panels for Eli Lilly, Merck and Novo Nordisk. Please see the full study for the other authors’ relevant financial disclosures.