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Coadministration of phentermine, lorcaserin increases weight loss, not adverse events in adults with obesity
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Adults with obesity assigned combination phentermine and lorcaserin therapy for 12 weeks saw greater weight loss compared with either agent alone, without an increase in potentially serotonergic adverse events, according to findings from a pilot safety study published in Obesity.
“In clinical studies, coadministration of serotonergic and noradrenergic drugs has led to additive weight loss,” Steven R. Smith, MD, chief scientific officer of Florida Hospital Research Services and scientific director at the Translational Research Institute for Metabolism and Diabetes at the Sanford Burnham Prebys Medical Discovery Institute, and colleagues wrote. “However, phentermine may be associated with increased serotonergic activity. Lorcaserin is a serotonergic agent; therefore, coadministration with phentermine could theoretically result in serotonergic events, adversely impacting safety.”
In a double blind, randomized controlled trial, Smith and colleagues analyzed data from 235 patients with BMI at least 30 kg/m² or BMI between 27 kg/m² and 29.9 kg/m² and at least one weight-related comorbidity, from 12 sites in the United States, between October 2013 and September 2014. Researchers randomly assigned patients to 10 mg lorcaserin hydrochloride (Belviq, Eisai) twice daily plus placebo; lorcaserin twice daily plus 15 mg immediate-release phentermine hydrochloride once daily plus placebo once daily; or lorcaserin twice daily plus phentermine twice daily. Randomization was stratified by BMI. Researchers instructed patients to take medications concurrently, once in the morning and again midafternoon, to reduce potential phentermine-associated insomnia. Follow-up occurred at 1, 2, 4, 8 and 12 weeks; a telephone safety assessment took place 3 to 4 weeks after patients received their last dose; all patients received ongoing one-on-one counseling. Primary endpoint included nine common, potentially serotonergic adverse events: dry mouth, headache, dizziness, fatigue, insomnia, nausea, diarrhea, vomiting and anxiety.
Within the cohort, 44 patients (18.7%) discontinued the study drug before week 12; most discontinuations occurred in the combination lorcaserin/phentermine twice-daily group, in which 20 patients (25.3%) did not complete the trial, according to the researchers.
During the study, 94 of 235 patients reported at least one of the prespecified adverse events; 37.2% in the lorcaserin twice-daily group; 42.3% in the lorcaserin, phentermine and placebo group; and 40.5% in the combination lorcaserin/phentermine twice-daily group. Discontinuation of study medication due to adverse events was more than twice as high in the combination lorcaserin/phentermine twice-daily group as in the lorcaserin twice-daily/placebo group (11.4% vs. 5.1%).
At 12 weeks, patients who completed therapy in the combination lorcaserin/phentermine twice-daily group were more likely to experience at least 5% weight loss vs. patients in the lorcaserin/ placebo group and the lorcaserin, phentermine and placebo group (84.2% vs. 33.3% and 68.2%, respectively).
“This pilot study suggests that coadministration of phentermine 15 mg once daily or twice daily with lorcaserin 10 mg twice daily did not appear to increase the incidence of nine prespecified potentially serotonergic [adverse events], but did significantly increase weight loss compared to lorcaserin 10 mg twice daily alone,” the researchers wrote. “Further study of lorcaserin/phentermine combination therapy for weight management should be considered.” – by Regina Schaffer
Disclosure: Eisai Inc. funded this study. Editorial support was provided by Imprint Science, New York, and was funded by Eisai. Smith reports receiving research grants or consulting fees from Amylin Pharmaceuticals, Arena, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai Inc., Elcelyx, Eli Lilly, Five Prime Therapeutics, GlaxoSmithKline, Ionis Pharmaceuticals, NGM Biopharmaceuticals, Novo Nordisk, NuSi, Orexigen, Pfizer, Piramal Life Sciences, Takeda and Zafgen. He is also an equity stakeholder in Jenrin Discovery and Zafgen. Please see the full study for the other authors’ relevant financial disclosures.
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