Are Two Drugs Better Than One?

Double-teaming weight-loss meds is perfectly legal and might help you drop pounds. But before you consider trying this trend, be sure you know the risks

By Liz Brody
Photograph: Illustrated by Shout

“Do you want to come back to that question?” the interviewer on the phone asked.

Jennifer Sibley’s mind went blank. She gripped her cordless a little tighter and looked around her home office. No, she didn’t want to come back to that question; as a seasoned advertising executive who’d been unemployed for a year, she wanted to nail the question and get the job. She’d already downloaded plenty of research about her potential employer and had a file of notes on her computer screen to help her produce a good answer. But she couldn’t seem to focus; the interviewer’s words just eddied around in her brain. The more she tried to grab onto an idea, the less she succeeded.

She didn’t get that job. Nor did she get the next one, with a chamber of commerce, after another interview (face to face this time) in which she couldn’t compose her thoughts. “That’s when I stopped taking the pills,” recalls Sibley, who lives in central Pennsylvania. “I came home and thought, It’s not worth it. These drugs are making me nutty.”

“These drugs”—phentermine, an appetite suppressant she bought on the Internet, and topiramate (brand name Topamax), an anticonvulsant she got from her family doctor—weren’t supposed to make Sibley flaky; they were intended to help her drop the extra five to 10 pounds she’d been unable to lose while unemployed. Faced with a dieting plateau, Sibley had turned to what’s known as combo-pilling, taking two medications that together are supposed to bring about more weight loss, with fewer side effects, than one alone. The cocktail Sibley chose is nicknamed phen-Topamax, but many other possible couplings, composed of appetite suppressants, antidepressants and other drugs, are being used.

Combo-pilling has been gaining appeal among dieters, doctors and pharmaceutical companies, in part because single diet drugs have not been a great success. (See “Guide to Diet Pills,” below.) After sibutramine (Meridia) was taken off the market last October, there was only one drug left that was approved by the FDA for treating obesity for more than a few weeks: orlistat (Xen-ical by prescription or Allī over the counter). But even though orlistat is the only long-term option for consumers, many dieters eschew it because they can experience side effects (oily stains on their underwear, for example) if they eat fat-heavy meals. To many, combo--pilling begins to seem like the answer.

While there are no comprehensive data on how many Americans are taking two diet drugs simultaneously, a study in the March 2009 issue of Obesityrevealed that 65 percent of weight specialists belonging to the American Society of Bariatric Physicians who responded to a survey are prescribing unapproved, or “off label,” drug combinations like phen-Topamax. This practice is perfectly legal. In fact, one out of five common drugs for adults is prescribed off label, according to a well--regarded 2006 analysis in the Archives of Internal Medicine.The theory is that as long as a drug has been approved and is on the market, physicians may use it as they see fit. However, while this leeway has created some happy surprises (such as the discovery that migraines can be treated with Botox), it also exposes patients to a medical gray zone where, without FDA-vetted research, they are completely dependent on the wisdom of their doctors.

One result: Most of the drug combos being used by dieters have not been tested in clinical trials conducted by drug companies or in rigorous studies led by academic researchers. There are also safety issues. For instance, when a drug manufacturer tried to market a single pill called Qnexa that combined the two medications Sibley took (although in different doses), the FDA rejected it over concerns about birth defects and cardiovascular risks. Yet both doctors and patients can point to success stories in which these medication regimens have led to weight loss without evident health damage.

Ultimately it’s up to each individual, in consultation with her physician, to decide whether the benefits of combo-pilling are worth the risks. Here, More takes a closer look.

First Published February 24, 2011

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