FDA Approval of First New Anti-obesity Drug in a Decade Highlights Benefits and Drawbacks

On June 27, 2012, the FDA approved Belviq (lorcaserin hydrochloride), as an addition to a reduced-calorie diet and exercise, for chronic weight management.  This is the first new anti-obesity drug approved in a decade by the agency; the drug is approved for use in adults with a body mass index (BMI) of 30 or greater (obese), or adults with a BMI of 27 or greater (overweight) and who have at least one weight-related condition such as high blood pressure (hypertension), type 2 diabetes, or high cholesterol (dyslipidemia).

According to the Centers for Disease Control and Prevention, more than one-third of adults in the United States are obese.  In 2008, medical costs associated with obesity were estimated at $147 billion; the medical costs paid by third-party payors for people who are obese were $1,429 higher than those of normal weight.

Belviq works by activating the serotonin 2C receptor in the brain. Activation of this receptor may help a person eat less and feel full after eating smaller amounts of food.  According to the FDA, the safety and efficacy of Belviq were evaluated in three randomized, placebo-controlled trials that included nearly 8,000 obese and overweight patients, with and without type 2 diabetes, treated for 52 to 104 weeks.  All participants received lifestyle modification that consisted of a reduced calorie diet and exercise counseling.  Compared with placebo, treatment with Belviq for up to one year was associated with average weight loss ranging from 3 percent to 3.7 percent.

About 47 percent of patients without type 2 diabetes lost at least 5 percent of their body weight compared with about 23 percent of patients treated with placebo. In people with type 2 diabetes, about 38 percent of patients treated with Belviq and 16 percent treated with placebo lost at least 5 percent of their body weight. Belviq treatment was associated with favorable changes in glycemic control in those with type 2 diabetes.

Lost in the discussion about the approval is that the approved labeling for Belviq recommends that the drug be discontinued in patients who fail to lose 5 percent of their body weight after 12 weeks of treatment, as these patients are unlikely to achieve clinically meaningful weight loss with continued treatment.  Whether the recommendation is noted or discussed with patients in a meaningful way is still to be determined.

Additionally, the FDA noted that Belviq should not be used during pregnancy.  Treatment with Belviq may cause serious side effects, including serotonin syndrome, particularly when taken with certain medicines that increase serotonin levels or activate serotonin receptors.  These include, but are not limited to, drugs commonly used to treat depression and migraine. 

In 1997, the weight-loss drugs fenfluramine and dexfenfluramine were withdrawn from the market after evidence emerged that they caused heart valve damage through related activation of the serotonin 2B receptor on heart tissue. When used at the approved dose of 10 milligrams twice a day, Belviq does not appear to activate the serotonin 2B receptor.

Because preliminary data suggested that the number of serotonin 2B receptors may be increased in patients with congestive heart failure, the FDA noted that Belviq should be used with caution in patients with this condition.  The drug’s manufacturer will be required to conduct six postmarketing studies, including a long-term cardiovascular outcomes trial to assess the effect of Belviq on the risk for major adverse cardiac events such as heart attack and stroke.  Other contraindications of Belviq in non-diabetic patients include headache, dizziness, fatigue, nausea, dry mouth, and constipation.