Diet Drug Controversies

The FDA recently approved two new weight-loss drugs and literally within hours of the drugs being officially released a pharmaceutical rep for one of the companies left his card with me and a patient called wanting a prescription. In the weeks that followed, full-page ads for the drugs began appearing in every medical journal I read regularly and I noticed a slight, but measurable, increase in the pharmaceutical junk mail that arrives daily.

The medical term for most weight-loss drugs is “anorectic agents” from anorexia, the term for no appetite. The only drug for weight loss that doesn’t affect appetite is Xenical (now sold over the counter as alli), which doesn’t affect appetite but works instead by blocking intestinal fat absorption. Alli provides a novel but challenging weight-loss mechanism: you leak the mega-caloric grease from your pepperoni pizza into your underwear.

Most of the commonly prescribed anorectics are variations on the amphetamine molecule and have been around for decades. Amphetamines are the same meds used for attention deficit disorder, and indeed parents starting their children on drugs like Adderall or Vyvanse are instructed to make sure the child remembers to eat because during the first weeks of treatment appetite plummets. Fortunately, this side effect goes away and within eight weeks or so the child’s appetite returns to normal.

All this is precisely why using any of the amphetamines for weight loss has been so disappointing. You’ll get eight weeks of appetite suppression and then nothing. You may lose some weight during those weeks, but then, thinking you’ll gain it back if you go off the drug, you find yourself asking for refill after refill but not losing another ounce.

Pharmaceutical researchers tweaked the molecules of various antidepressants to provide a second group of anorectics. The most notorious of these were fenfluramine (Pondimin) and dexfenfluramine (Redux). Taking either with a separate prescription for the amphetamine phentermine produced the now legendary fen-phen. The combo did trigger weight loss and the public loved it, but there was a problematic side effect–permanent heart valve damage. Ultimately, the FDA, working in slo-mo when compared to Europe, withdrew it.

Another short-lived med in this tweaked-antidepressant group was Meridia (sibutramine), also withdrawn after a few years because more heart damage issues were being reported. In each case–Pondimin, Redux, and Meridia–the US was virtually the last country with an FDA-type organization to yank them from pharmacy shelves. Ironically, the three are still being manufactured and sold online through countries where there is no drug safety monitoring. Meridia even surfaced (at twice the recommended dose) in an herbal weight-loss tea from China.

The current antidepressant variant most widely prescribed for weight loss is diethylpropion (Tenuate), a cousin of bupropion (Wellbutrin), which, like the others, works for a while but then stops. Recently, patients began to report unexplained weight loss as a side effect of yet another drug, Topamax (topiramate), a med used to prevent migraines.

Suddenly, the nostrils of pharmaceutical CEOs began to twitch and dilate, sniffing serious profits in the air.

Qsymia and Belviq

And thus the first of the new weight-loss drugs released this year, Qsymia (don’t ask me how to pronounce it) by Vivus, Inc, simply combines phentermine and topiramate into one pill. As both these drugs have long been available generically, doctors had already prescribed the two via separate prescriptions as a weight-loss aid. Like the other amphetamine-based anorectics, the combination seemed to work for about eight weeks and then stopped. There is no reason to expect a different result from the seriously overpriced combo-drug Qsymia.

The second new medication this year, Belviq (bell-veek), is the brand name of yet another antidepressant variant called lorcaserin. Despite the bad luck other manufacturers had with fen-phen and Meridia (massive lawsuits still pending), the manufacturer, Arena Pharmaceuticals, apparently is betting on the rising incidence of obesity. The recent declaration from the AMA that obesity is a disease guarantees that health insurance companies will be required to pick up the tab on weight-loss meds.

Arena was clearly disappointed when the FDA rejected Belviq in 2010 for safety concerns, going back to the drawing board and plugging away, desperate for approval.

Keeping in mind that all–repeat all–pharmaceutical studies are to be regarded with great skepticism, the new data presented by Arena was enough to convince the FDA to approve Belviq, even though some on the committee felt the weight-loss effect was marginal at best. Interestingly, when Belviq finally garnered approval, the Drug Enforcement Administration (DEA) stepped in and classified it as a Schedule IV controlled drug because some users reported hallucinations and the possibility of psychiatric dependency existed.

Much to the disappointment of both Vivus and Arena, physicians in the US, aware of the problems with this whole class of medications, are simply not prescribing them with much enthusiasm. Sales of both drugs and their company stocks are flat.

You might be wondering if the FDA should have approved them in the first place

That question was answered quite vociferously in the British Medical Journal by Sidney Wolfe, MD, an US physician who directs Public Citizen, a not-for-profit consumer awareness group much concerned with the safety of pharmaceuticals. He points out that Europe’s FDA counterpart, the European Medicines Agency (EMA), permanently rejected both Qsymia and Belviq because there were too many unanswered questions about long-term side effects. Dr Wolfe thinks it shameful that either of these ever made it to market here in the first place.

In fact, there was no unanimity among the doctors on the FDA committee, with one cardiologist seriously concerned that a heart valve issue could surface years in the future. Also, do remember that the weight-loss effects of each drug were minimal in comparison to placebo.

If you’re interested, the only prescription weight-loss medication I’m currently prescribing is HCG (human chorionic gonadotropin), which I’ve written about in the past. With HCG, I’m insistent that patients using it follow our rules. Ours is a supervised weight-loss program requiring regularly scheduled visits with one of our nutritionists, Marla Feingold or Seanna Tully. What you won’t get from me is an HCG prescription, a smile, and my best wishes for success.

My advice going forward: when you start seeing web, TV, and magazine ads for Qsymia and Belviq, press the “ignore” button in your brain.

Be well,
David Edelberg, MD