It’s an exciting time to be in weight loss. The FDA recently approved 2 new drugs for weight loss. The first to be approved was Belviq (lorcaserin) (Arena Pharmaceuticals) and the second approved was Qsymia (Phentermine/Topiramate ER) (Vivus, Inc.).
Belviq/Lorcaserin
Lorcaserin is a selective serotonin 2C agonist that decreases the intake of food. The last serotonin agonist used for weight loss, fenfluramine, was nonspecific and, unfortunately, also stimulated the serotonin 2B receptors expressed on cardiac valves. This stimulation is thought to have thickened the leaflets and chordae tendineae of the cardiac valves leading to damage and cardiac fibrosis. Fenfluramine was taken off of the market in 1997. Lorcaserin is 100 times more specific for the 2C receptors than the 2B receptors.
The Studies.
The first study to be published supporting lorcaserin was called Behavioral Modification and Lorcaserin for Overweight and Obesity Management or BLOOM.[1] In this trial, patients with body mass indices (BMIs) of 30 to 45kg/m2 or 27 to 45kg/m2 with a least one obesity-related comorbidity were enrolled. Patients with pre-existing valvulopathy, persistently elevated blood pressure, pregnancy, or diabetes were excluded. In this trial, 3,182 patients in a double-blind fashion were randomly assigned to receive either lorcaserin 10mg twice daily (BID) or placebo BID for 52 weeks./
In the lorcaserin group, 47.5 percent of patients lost five percent or more of their body weight with an average weight loss of 5.8±0.2kg. In the placebo group, 20.3 percent of patients lost five percent or more of their body weight with an average weight loss of 2.2±0.1kg.
Additionally, weight was maintained in more patients who continued to use lorcaserin (67.9%) than placebo (50.3%). Among the 2,472 patients evaluated at Year 1 and 1,127 patients evaluated at Year 2, the rate of cardiac valvulopathy was not increased with use of lorcaserin (Lorcaserin group 2.7% and placebo 2.3%).
In the second study, the Behavioral Modification and Lorcaserin Second Study for Obesity Management or Blossom,[2] 4,008 patients with BMIs of 30 to 65kg/m2 or 27 to 29.9kg/m2 with one obesity-related comorbidity were randomly assigned to one of the following three groups: 1) lorcaserin 10mg BID, 2) lorcaserin 10mg once daily (QD), or 3) placebo. Patients taking lorcaserin who lost at least five percent of their baseline weight was achieved as follows: lorcaserin 10mg BID, 22.6 percent; lorcaserin 10mg QD, 17.4 percent; and placebo, 9.7 percent.
Patients with recent cardiovascular events, diabetes, or those who had taken selective serotonin reuptake inhibitors (SSRIs) in the past year were excluded. Patients who discontinued the study citing lack of efficacy as the reason were 2.4% in the higher dose, 3.1% in the lower dose, and 3.9% in the placebo group, respectively. Dropouts due to adverse events were 7.2, 6.2, and 4.6 percent in the three groups, respectively. Adverse events included headache, upper respiratory infection, nausea, dizziness, and fatigue. Adverse events occurred in 82.6, 81.5, and 75.3 percent of patients, respectively.
Using a modified intention-to-treat-last-observation-carried-forward analysis, patients taking Lorcaserin lost an average of 5.8kg at 52 weeks, which was 2.9kg more than patients on placebo.
Summary
It’s still early in the game for both Belviq and Qsymia. Time will determine the final clinical utility of these drugs and the best uses for them. As of now, we should be excited about these new options being made available to our patients and the future of medical obesity treatment.
References
1. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of Lorcaserin for weight management. N Engl J Med. 2010;363:245–256.
2. Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: The BLOSSOM trial. J Clin Endocrinol Metab. 2011;96:3067–3077.
By Craig Primack, MD