Two New Drugs Approved for Weight Loss Treatment

by Craig Primack, MD, FAAP

Bariatric Times. 2012;9(8):11

Funding: No funding was provided in the preparation of this manuscript.

Financial disclosures: The author reports no conflicts of interest relevant to the content of this article.

It is an exciting time to be in weight loss. In the past month, the united States Food and Drug Administration (FDA) has approved two new drugs for weight loss. The first to be approved was lorcaserin. It will be commercialized by Arena Pharmaceuticals (San Diego, California) and Eisai Inc. (Woodcliff Lake, New Jersey) under the brand name Belviq. The second approved was a drug that we covered in the April 2012 installment of “Medical Methods in Obesity Treatment.” The column discussed the history of phentermine/extended-release topiramate (Qnexa, Vivus, Inc., Mountain View, California). At the last minute, the FDA requested a drug name change from Qnexa to Qsymia. Qsymia is expected to be available in late 2012. Belviq is expected to be available in December 2102 or January 2013.

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 chordinae tendinae 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 data. 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 (loracaserin 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 seratonin reuptake inhibitors (SSRIs) in the past year were excluded. Patients who discontinued the study citing lack of efficacy as the reason were 2.4, 3.1, and 3.9 percent, 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.

Final Thoughts
It is still early in the game for both Belviq and Qsymia, which have just been aprroved by the FDA and are still not available on the market. Also, both drugs will likely not be covered initially by insurance.

Time will determine the final clinical utility of Belviq and Qsymia, but as of now, we should be excited about these new options being made available for 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 Endocinol Metab. 2011;96:3067–3077.

Category: Medical Methods in Obesity Treatment, Past Articles