FDA approves Alli, the first and only over-the-counter weight-loss drug

The Food and Drug Administration approved Alli, a 60 mg capsule of orlistat made by GlaxoSmithKline Consumer Healthcare, for over-the-counter sale on February 7, 2007 ^[1]. It is the first FDA-approved over-the-counter weight-loss pill, intended for overweight adults 18 and older who also follow a reduced-calorie, low-fat diet ^[1][2].

Alli is a half-strength version of the prescription drug Xenical ^[2]. Xenical is sold in 120 mg doses, usually taken three times a day; Alli capsules are 60 mg and are taken three times daily with each fat-containing meal ^[2]. The active ingredient, orlistat, blocks fat from being absorbed in the intestine — about 25 percent of the fat a person eats — so the unabsorbed fat passes out of the body ^[2].

The drug is not meant for people who are not overweight or for those who have trouble absorbing food ^[2]. The FDA-approved consumer information recommends talking to a doctor first for people taking blood thinners or being treated for diabetes or thyroid disease ^[2].

What the trial numbers show

Weight loss with orlistat is modest. Clinical trials indicate orlistat users are more likely to lose at least 5% of their starting weight than dieters who do not take it, and while they often regain weight, they keep off more than other dieters ^[2]. In one study cited by critics, participants taking orlistat plus diet and exercise went from an average of 242 pounds to 229 pounds, while the placebo plus diet and exercise group went from 242 pounds to 235 pounds — and that study used a dose twice as high as Alli's ^[2].

Side effects are the well-known trade-off. The most common are "oily spotting, loose stools, more frequent stools that may be hard to control," and gas ^[2]. Those effects get worse when people eat more fat, which is part of why the drug can push users toward a low-fat diet ^[2]. Orlistat also partially blocks absorption of fat-soluble vitamins A, D, E and K, though trial participants who took vitamin supplements alongside orlistat did not develop deficiencies ^[2].

The approval came over objections. Public Citizen's Health Research Group filed a citizen petition on April 10, 2006, asking the FDA to pull Xenical from the market and deny approval of Alli, pointing to earlier findings of increased breast cancer among orlistat users and evidence of aberrant crypt foci, which the group described as a possible precursor of colon cancer ^[2]. The FDA's response, dated the same day as the approval, did not deny that questions about long-term safety remained but said the evidence was not sufficient to rescind approval, and the agency maintains orlistat is safe and effective ^[2].

Why it matters for patients

An over-the-counter approval changes who can get a weight-loss drug and how. No prescription, no office visit, and no pharmacist gatekeeping — but also no built-in medical follow-up, which matters for people on blood thinners or being treated for diabetes or thyroid disease ^[2].

It also sets a regulatory line. Alli went through FDA review as a drug, with a Drug Facts label the agency controls; products sold as dietary supplements do not go through that kind of pre-market approval. Whether other non-prescription weight-loss drugs have been approved since is not addressed in the sources available here.

Expectations matter too. The trial figures above describe a difference of several pounds over a placebo group that also dieted and exercised, not the kind of double-digit percentage losses seen with newer injectable medicines ^[2].

What happens next

The label has continued to change. On June 10, 2026, the FDA approved revisions to the Alli 60 mg Drug Facts label warning of acute kidney injury, described as a rare side effect ^[1]. The updated labeling tells consumers to ask a health care provider before use if they have ever had kidney disease or kidney stones, and to stop using the product and contact a doctor if they develop back or groin pain, painful urination, blood in the urine, swelling in the feet and legs, or less frequent urination ^[1].