Drug Profile

Do Not Use: This drug has not been shown to have long-term health benefits.

Orlistat (ALLI, XENICAL), like other diet drugs, is approved by the Food and Drug Administration (FDA) for use in conjunction with a reduced-calorie diet. Also like other diet drugs, orlistat was approved without scientific evidence showing that there is a health benefit for those who use it. In other words, there is no evidence that orlistat, or any diet drug, will reduce risk of premature death or illness associated with long-term obesity and inactivity.

An editorial published in a 1998 issue of The New England Journal of Medicine summed up how little is known about the effect of weight loss and health:

Given the enormous social pressure to lose weight, one might suppose there is clear and overwhelming evidence of the risks of obesity and the benefits of weight loss. Unfortunately, the data linking overweight and death, as well as the data showing the beneficial effects of weight loss, are limited, fragmentary, and often ambiguous. Most of the evidence is either indirect or derived from observational epidemiologic studies, many of which have serious methodologic flaws. Many studies fail to consider confounding variables, which are extremely difficult to assess and control for in this type of study. For example, mortality among obese people may be misleadingly high because overweight people are more likely to be sedentary and of low socioeconomic status. Thus, although some claim that every year 300,000 deaths in the United States are caused by obesity, that figure is by no means well established.[1]

Side effects

Unlike other obesity drugs, orlistat prevents enzymes in the gastrointestinal tract from breaking down dietary fats into smaller molecules that can be absorbed by the body. Thus, absorption of fat is decreased by about 30 percent, leading to orlistat’s most common adverse effects: oily spotting, gas with discharge, fecal urgency, fatty/oily stools and frequent bowel movements. Because orlistat reduces the absorption of some fat-soluble vitamins and beta-carotene, patients must take a supplement that contains fat-soluble vitamins (A, D, E and K) and beta-carotene.

The most serious risks associated with orlistat include severe liver injury, acute pancreatitis and acute renal failure.

Liver injury

The product label for orlistat now includes new safety information regarding severe liver injury. Signs and symptoms of liver injury include itching, yellow eyes or skin, dark urine, light-colored stools and loss of appetite.[2]

In 2006, The American Journal of Medicine published a case report of severe liver injury caused by orlistat. Health care practitioners should be aware that a possible association of liver toxicity with orlistat has been reported, and though there have been few cases of serious adverse liver-related effects, care should be taken when prescribing this drug to patients.[3]

Kidney disease, hypothyroidism and convulsions

In July 2010 the French medical journal Prescrire International published an article concerning the adverse effects of and special warnings associated with the use of orlistat. The information addressed patients with kidney disease, hypothyroidism and convulsions. According to the article, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended changes to the drug product information based on reports received. The article stated that 45 cases of hypothyroidism and other thyroid disorders were reported in patients taking levothyroxine and orlistat, and 12 cases of convulsions were reported in patients taking antiepileptics and orlistat.[4]

While conducting a routine post-marketing safety review of orlistat, the FDA made an alarming finding: 37 cases of gallstones in patients of all ages between 1999 and 2006.

Studies show …

In December 2011, Prescrire International published an article reviewing information on cases of liver and renal injury associated with orlistat use. The authors found that the harm or risk of using orlistat outweighed the benefit of the drug.[5]

Regulatory actions surrounding orlistat

1997: In May, Public Citizen’s Health Research Group testified before an FDA advisory committee that reviews diet drugs to urge against orlistat's approval unless there was evidence that it offers a health benefit by reducing the illness and death associated with obesity.[6] Because this drug has not been shown to confer a health benefit, the FDA-approved product label states: “The long-term effects of orlistat on morbidity and mortality associated with obesity have not been established.”[7]

2006: Public Citizen petitioned the FDA on April 10, 2006, to immediately remove orlistat from the market. The petition was based on research showing that orlistat can cause precancerous changes in the lining of the intestines (called aberrant crypt foci).[8]

2007: In January, XENICAL’s product label was revised to include information based on post-marketing reports of pancreatitis (inflammation of the pancreas) with the use of orlistat. Information from clinical trial data suggested an association between pancreatitis and orlistat; however, a causal relationship has not been definitively established.[9]

One month later, in February, Public Citizen admonished the FDA’s decision to approve orlistat over-the-counter (now available as ALLI) as “reckless”:

At a time when colon cancer is a leading cause of death and disease in the United States, the Food and Drug Administration’s decision to approve, for over-the-counter use, a drug that clearly causes pre-cancerous lesions of the colon (aberrant crypt foci or ACF) is the height of recklessness and shows a profound lack of concern for the public’s health.[10]

2009: The FDA issued an early communication that they have received reports of serious liver injury associated with use of orlistat and that they were reviewing this information along with other data received by the FDA.[11]

2010: The FDA issued an advisory that it had updated the drug label for orlistat with new safety information. This information related to 13 reports of severe liver injury associated with the use of orlistat.

2011: On April 14, 2011, Public Citizen petitioned the FDA to immediately ban both the prescription and the over-the-counter forms of orlistat because this drug exposes patients to serious risks that greatly outweigh their minimal clinical benefits. The petition stated that the drug not only can damage the liver but also, based on information obtained from FDA adverse reaction files, has been associated with 47 cases of acute pancreatitis and 73 cases of kidney stones.

The 2011 petition was the second Public Citizen appeal to have XENICAL taken off pharmacy shelves. The FDA rejected the earlier-mentioned 2006 petition.

2013: In October 2013, the FDA issued an advisory on reports of convulsions in patients treated with orlistat and antiepileptic drugs.[12]

2016: In August 2016, an FDA advisory stated that drugs used to treat human immunodeficiency virus (HIV) may not work as well when taken with orlistat. Orlistat also may interact with cyclosporine, levothyroxine, warfarin, amiodarone, and anti-seizure drugs.[13]