FDA approves Alli, the first over-the-counter weight-loss pill

The FDA approved Alli on February 7, 2007, clearing orlistat 60 mg capsules for sale without a prescription and making it the first FDA-approved over-the-counter weight-loss pill ^[1][2]. The product is made by GlaxoSmithKline Consumer Healthcare ^[1][2].

Alli contains the same active ingredient as the prescription weight-loss drug Xenical, but at half the dose. Xenical is sold in 120 mg capsules; Alli capsules are 60 mg and are taken three times a day with each meal that contains fat ^[2]. Orlistat works in the intestine, blocking absorption of some of the fat a person eats so that it passes through the digestive system instead ^[2]. It blocks about 25 percent of the fat consumed ^[2].

The FDA approved Alli for weight loss in overweight adults 18 and older, to be used along with a reduced-calorie, low-fat diet ^[1]. The program promoted with the drug recommended starting a diet before taking it, along with exercise ^[2]. It is not intended for people who have problems absorbing food or for people who are not overweight ^[2].

Side effects and how much weight people lost

The most common side effects are "oily spotting, loose stools, more frequent stools that may be hard to control," and flatulence ^[2]. GlaxoSmithKline's myalli.com website suggested wearing dark pants and staying near a bathroom, and said that strictly following the recommended low-fat, low-calorie diet and exercise plan can reduce those effects ^[2]. Orlistat also partially blocks absorption of fat-soluble vitamins A, D, E and K, but patients in clinical trials did not develop vitamin deficiencies when they took vitamin supplements at the same time ^[2].

On average, the weight loss has been modest. Clinical trials indicate that orlistat users are more likely to lose at least 5 percent of their starting weight than other dieters ^[2]. Even so, most people who take orlistat or Xenical do not lose 5 percent of their weight or more, which for someone starting at 200 pounds is about 10 pounds ^[2]. In one study, the group taking orlistat plus diet and exercise went from 242 pounds to 229 pounds, while the placebo group on diet and exercise went from 242 pounds to 235 pounds. The orlistat dose in that study was twice the dose in Alli ^[2].

Safety questions have been raised since before approval. Public Citizen Health Research Group petitioned the FDA on April 10, 2006, asking the agency to remove Xenical from the market and deny approval for Alli, pointing to previous studies that found a significant increase in breast cancer among orlistat users and evidence of a significant increase in aberrant crypt foci, which research indicates could be a precursor of colon cancer ^[2]. In its response, the FDA did not deny that there were unanswered questions about long-term safety, but said the evidence was not sufficient to justify withdrawing approval. The agency maintains that orlistat is safe and effective ^[2].

Later label change

On June 10, 2026, the FDA approved changes to the Drug Facts label for Alli to warn about acute kidney injury, described as a rare side effect of the medication. The labeling now advises consumers to ask a health care provider before using Alli if they have ever had kidney disease or kidney stones. It also tells consumers to stop using Alli and ask a doctor if they develop symptoms of kidney injury or kidney stones, such as back or groin pain, painful urination, blood in the urine, feet and leg swelling, or less frequent urination ^[1].

Why it matters for patients

Alli can be bought without a prescription by adults 18 and older who are overweight, but the approval is tied to using it with a reduced-calorie, low-fat diet ^[1][2]. People who take it and eat fatty meals are more likely to get the unpleasant gastrointestinal effects, which is why the drug's own materials pushed diet and exercise alongside it ^[2].

Expectations matter here. In the studies reviewed, most people taking orlistat did not lose 5 percent of their body weight or more, and the difference between the drug and a placebo in at least one study was small ^[2]. The trial that showed a 13-pound average loss used twice the dose found in Alli ^[2].

Anyone with a history of kidney disease or kidney stones is now told to check with a health care provider before using Alli, and to stop and seek medical advice for symptoms such as back or groin pain, painful urination, blood in the urine, swelling in the feet and legs, or urinating less often ^[1]. Because orlistat can reduce absorption of vitamins A, D, E and K, the trial evidence on vitamin deficiency involved people who took supplements at the same time as the drug ^[2].

The cancer question raised in the 2006 petition has not been resolved in the labeling, and the FDA's position remains that the evidence did not justify removing the drug from the market ^[2].