Weight loss without cardiac side effects

Weight loss without cardiac side effects

A new weight-loss medication may soon be available in the United States. Arena pharmaceuticals has filed a new drug application with the FDA for lorcaserin, a selective serotonin 2C-receptor agonist, and will likely get a formal review this fall. Unlike previous nonselective serotonergic agonists such as fenfluramine and dexfenfluramine, which were effective at causing weight loss, but also inhibited serotonin 2B receptors in the heart and were associated with valvulopathy, lorcaserin is specific for the serotonin 2C receptor in the brain.

Results from a company-sponsored study were published in the in New England Journal of Medicine and validate the effectiveness of the drug. The phase III trial was conducted at 98 academic and private trial sites, where 3180 patients were randomly assigned to receive lorcaserin 10 mg or placebo twice daily. After 1 year, patients receiving the active drug were randomly reassigned in a 2:1 ratio to continue to receive lorcaserin or change to placebo. All patients were age 18-65 years with a BMI of 30-45 or 27-45 kg/m² with one coexisting condition, including hypertension, dyslipidemia, cardiovascular disease, impaired glucose tolerance, or sleep apnea. Patients were also counseled on lifestyle modification. Echocardiography was done at baseline and every 6 months thereafter.

At the end of 1 year, 47.5% of patients receiving lorcaserin lost 5% or more of their baseline body weight as compared with 20.3% of patients receiving placebo (P < 0.001). The average patient in the lorcaserin group lost 5.8% of their body weight compared with 2.2% in the placebo group (P < 0.001), and more patients in the active treatment group lost 10% or more of their baseline body weight than in the placebo group (22.6% vs 7.7%; P < 0.001). In those who lost weight with the active drug, the loss was maintained in a greater proportion of patients who continued to receive lorcaserin in year 2 compared to those who were reassigned to placebo (67.9% vs 50.3%; P < 0.001). Markers of cardiovascular risk were improved in the active treatment group including C-reactive protein, fibrinogen levels, lipid levels, and insulin resistance. Systolic and diastolic blood pressures also decreased slightly in the lorcaserin group. Significantly, there was no evidence of cardiac valvulopathy found with use of lorcaserin and the rate of serious side effects was similar in the two groups.

The authors conclude that lorcaserin was associated with significant weight loss and improved maintenance of weight loss as compared to placebo (N Engl J Med 2010;363:245-256). Already being tagged the new, safe "diet drug," it is a sure bet that approval of lorcaserin will be associated with tremendous interest from our patients.