Are the New Generation of Diet Drugs Safe?

Mindful of the havoc created by fen-phen, a regimen the FDA never approved (or even rigorously studied), the agency has issued clear-cut indications for all four new drugs. To qualify for treatment, you must have a BMI of 30 or above, or 27 or above with at least one comorbidity—that is, a weight-related health problem, which could be anything from arthritis of the knee to elevated blood sugar. Probably half of adult America could sail across that bar. Pyle didn’t technically make the cut, but doctors have leeway to go off-label when they feel it’s medically justified. “We run into this gray zone,” says her doctor, Ken Fujioka, MD, of San Diego’s Scripps Clinic, a top obesity researcher and clinician. “But that said, we all do it.”

If nothing else, the research poured into building a better weight-loss drug has given us a better understanding of our eating habits. “Only part of why we eat is hunger,” says Donna Ryan, MD, a drug-industry consultant and a senior editor of the journal Obesity. “After you’ve eaten something, your gut sends satiety signals to the brain,” which shuts down your hunger pangs. All the new drugs suppress the appetite: Qsymia, Saxenda, and Belviq do it by either dialing hunger down or satiety up; Contrave, however, desensitizes the brain’s reward circuitry. “The other reason we eat is encapsulated in our reward circuits,” Ryan says. “You may have a dessert even if you’re full, because sweet foods—and savory ones such as chips—have a high reward value.”

Qsymia wins for biggest weight-loss advantage—an estimated 10 percent of body weight, according to some experts. A combo drug, its larger component is topiramate, which works on several brain chemicals to calm nerve activity. It was first approved in 1996 as an antiseizure med—brand name Topamax—and later as a treatment for migraines. “Models used it for years to stay thin,” says Beverly Hills endocrinologist Eva Cwynar, MD, author of The Fatigue Solution, who has developed a weight-management sideline for her upscale clientele. Fujioka admits that our understanding of how topiramate works is incomplete, but preliminary research and his own clinical experience suggest that it’s an effective counter to binge eating. “About 10 to 15 percent of the population will eat very large portions,” he says, “and feel very out of control—’I won’t eat four or five crackers, I’ll eat the whole box,’ they’ll tell me.”

The smaller chunk of Qsymia is none other than the former fen-phen component phentermine, the grandmother of weight drugs, which entered the market in 1959. In reasonable doses, phentermine itself isn’t toxic. It’s a stimulant similar to amphetamines, akin to those found in ADHD drugs, that works on hunger centers in the brain. “But it does give you a high,” Apovian says. “Suddenly you feel like going to the gym or vacuuming all night—so there is some potential for abuse.”

Obesity specialists consider Qsymia’s 7.5-milligram dose of phentermine a reasonable risk unless you have cardiovascular issues—in which case any central nervous system stimulant is dangerous. This past year, Lomaira, a stand-alone, low-dose 8-milligram phentermine pill for weight loss, also hit the market.

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