If you are among millions of Americans fighting the “Battle of the Bulge”, you are not alone. In America there is an epidemic of obesity. One third of adults are overweight and another third are obese, many morbidly obese. This sets the stage for other medical problems, including high blood pressure, type 2 diabetes, and high cholesterol, arthritis and other inflammatory problems, Alzheimer’s disease and cancer. Recent studies show that even when obese patients achieve control of blood pressure, diabetes and cholesterol with medications, their morbidity and mortality is higher than that of patients with normal weight.
Weight loss drugs in general have not had a great track record for safety. Both fen-phen (fenfluramine and phentermine combination) and Redux (dexfenfluramine), were withdrawn from the market in 1997 due to heart valve damage. Last year, Sibutramine (Meridia) was also pulled from pharmacy shelves due to concerns about heart problems.
After a 13-year hiatus, the FDA has approved 2 new drugs: Belviq® (lorcaserin) and Qsymia™ (a combination of 2 approved older drugs: the appetite suppressant phentermine and topiramate, which is used to treat seizures and migraines). The FDA rejected Qsymia a in 2010 when it was studied under the name Qnexa due to concerns of it tumorigenic activity in rats and possibly causing heart valve problems like a similar agent, fenfluramine, which was taken off the market over a decade ago for this reason. Since then, the drug manufacturer Vivus, agreed to rename the drug Qsymia to avoid confusion with another drug already on the market.
Lorcaserin is a seratonergic agent that binds on a different receptor than fenfluramine, and the incidence of valve issues in clinical trials is the same as placebo. In the “BLOSSOM” clinical trials with lorcaserin, patients received 10 mg twice daily of lorcaserin in addition to receiving physical activity counseling to exercise moderately for 30 minutes per day and dietary counseling that recommended keeping caloric intake at 600 kcal below estimated energy requirements. After one year, a higher percentage of patients receiving lorcaserin at either 10 mg daily or twice daily dosing lost 5%-10% of their baseline weight compared to placebo patients. 35% of placebo patients were still able to lose 5-15% of their bodyweight with lifestyle changes alone. Average weight loss with lorcaserin was 5.8 kg at 52 weeks. Side effects included headache, nausea and dizziness.
In another trial, the “CONQUER” trial, obese patients received either daily low dose or regular dose of Qnexa vs a placebo, and all patients participated in a lifestyle/behavioral modification program known as “LEARN” (lifestyle, education, attitudes, relationships, nutrition). After 56 weeks, the average weight loss was 2% in controls, 7% in low dose Qnexa and 9% with high dose. Side effects included dry mouth, constipation, and paresthesias. Topamax is a well-know teratogen, resulting in 4-5/1,000 cases of cleft palate when used during pregnancy, and thus should be used cautiously in women of child-bearing years.
These drugs will not be recommended to lose a few pounds, but rather for patients with BMIs over 27 with at least one obesity-related comorbidity. Suggested use is for one year, then a trial off of medications should be attempted. Beyond the effects of the medications, we know the importance of diet and exercise, and both of these trials indicate that with diet and exercise counseling and resultant lifestyle changes, many patients can lose at least 5% of their bodyweight in one year.