In the May 2017 issue of Obesity, Steven Smith, M.D. and coauthors performed a pilot study in 235 patients to assess the short-term tolerability of lorcaserin 10 mg twice daily monotherapy or when combined with phentermine 15 mg once daily or twice daily. Patients were assessed for weight loss over a 12 week period as well as potentially serotonergic adverse events (dry mouth, headache, dizziness, fatigue, insomnia, nausea, diarrhea, vomiting and anxiety). 37.2% of lorcaserin monotherapy group, 42.3% of the lorcaserin phentermine once daily group and 40.5% of the lorcaserin phentermine twice daily group reported potentially serotonergic adverse events. Headache and dry mouth were the most common adverse events. Adverse events leading to discontinuation were approximately double in the lorcaserin twice daily phentermine group compared to the lorcaserin monotherapy group. None of the potentially serotonergic adverse events were reported as serious and serotonin syndrome did not occur in any of the subjects. Mean weight loss was 3.3% in the lorcaserin monotherapy group, 6.7% in the lorcaserin phentermine once daily group and 7.2% in the lorcaserin phentermine twice daily group. A reduction of >5% of initial body weight was achieved in 28.2% of lorcaserin monotherapy subjects compared to 59.0% in lorcaserin phentermine once daily subjects and 70.9% in lorcaserin phentermine twice daily subjects.
This study evaluated combination pharmacotherapy with lorcaserin and phentermine which have distinct yet complimentary mechanisms of action. By targeting different signaling pathways, combination therapy has the potential to give better outcomes by overcoming adaptive mechanisms that can impede weight loss, thus improving efficacy. This study showed that the combination enhanced short-term weight loss but did not increase the incidence of potentially serotonergic adverse events. However, lorcaserin with twice daily phentermine did increase discontinuations compared to lorcaserin monotherapy and lorcaserin with once daily phentermine.