FDA Approval of OTC Weight-Loss Drug: Clinical Implications

GI Side Effects May Curb Appetite for the Drug

The low-dose formulation of orlistat (alli), the weight-loss drug recently approved by the FDA for over-the-counter (OTC) marketing, will begin to appear on pharmacy shelves this summer. This means that adults—overweight or not—who want to lose weight will no longer need monitoring by a physician to take this drug.

Will this new, low-dose formulation of an already existing drug (which in its higher dose is still only available by prescription) make a difference in combating the obesity epidemic?

Orlistat works by blocking the action of pancreatic lipase enzymes, thereby inhibiting the complete hydrolization of fat into fatty acids and glycerol and decreasing fecal fat absorption.

Several randomized, placebo-controlled trials have demonstrated significantly better weight loss in obese adults who were taking orlistat and following a weight-loss diet compared with adults taking a placebo and dieting. Orlistat has also been shown to improve hemoglobin A_1c in diabetic patients and to lower the risk of progressing to diabetes in those with impaired glucose tolerance.

The weight loss associated with the drug, however, is modest, and patients must continue taking the drug indefinitely to sustain the weight loss. In addition, unpleasant gastrointestinal (GI) side effects have been reported.

Although patients may only lose 10 to 15 lb with orlistat, experts generally welcome the drug. “Losing a small amount of weight does help,” said David S. Cooper, MD, director of the Division of Endocrinology at Sinai Hospital in Baltimore, Md. The modest weight loss is more likely to help patients avoid the complications of diabetes and hypertension, he emphasized, than to help them attain the cosmetic benefit that many overweight Americans seek. “Very few people lose more than 10% of their body weight.”

Dr Cooper suggested that although the OTC product may initially be popular, interest may wane over time as people encounter unpleasant side effects and fail to lose all the weight they would like to lose. And many people may eventually lose their enthusiasm for taking the drug 3 times daily, as the instructions require. “It takes a motivated person,” he said.

In requesting OTC status for orlistat, the manufacturer did not seek approval for children. Even though orlistat by prescription is indicated for children as young as 12 years, the company believes that overweight and obese children should be managed by a physician, according to Brian L. Jones, a spokesperson for GlaxoSmithKline. The company voluntarily added a special bar code that would alert a cashier to request proof of age if a young person tries to buy the drug without a prescription.

So although children may be protected, what is to protect against the drug being abused by young or older adults with eating disorders?

“We don’t think there is a big risk of abuse,” said Mr Jones. Because people with eating disorders generally eat a very low-fat diet, inhibiting fat absorption will not really help them lose more weight, he reasoned.

Experts tend to agree that orlistat is safe for adults who are not pregnant or nursing. “I think it will be very safe,” said Ken Fujioka, MD, director of the Center for Weight Management at the Scripps Clinic in San Diego.

But patients will need to cope with these unpleasant side effects that affect up to 1 in 4 patients:

• Abdominal cramping

• Oily fecal spotting

• Excess flatus.

Since orlistat also decreases absorption of fat-soluble vitamins, “people should be cautioned to be on a multivitamin,” added Dr Cooper.