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Review of the Diet Drug Orlistat

Worst Pills, Best Pills Newsletter article November, 2019

The obesity epidemic is a serious public health problem that continues to grow at a staggering rate in the United States and around the world.[1] Forty percent of all U.S. adults aged 20 years or older were considered obese in 2015 to 2016.[2] It is projected that this epidemic will afflict over 50% of the U.S. population by 2030.[3]

Obesity is defined as a body mass index (BMI; an indicator of body fat based on height and weight) of 30 or greater. A normal BMI for an adult is between...

The obesity epidemic is a serious public health problem that continues to grow at a staggering rate in the United States and around the world.[1] Forty percent of all U.S. adults aged 20 years or older were considered obese in 2015 to 2016.[2] It is projected that this epidemic will afflict over 50% of the U.S. population by 2030.[3]

Obesity is defined as a body mass index (BMI; an indicator of body fat based on height and weight) of 30 or greater. A normal BMI for an adult is between 18.5 and 24.9.[4] This condition is associated with an increased risk of developing serious diseases, including diabetes, heart disease, stroke and some types of cancer, which are among the leading causes of death in the U.S.[5] It is a complex disorder that is caused by various factors, including diet, lifestyle, physical activity and genetics.

Due to the many contributing influences that lead to excess body weight, diet drugs are not “magic pills” that can quickly reverse obesity or its effects. Importantly, there is no evidence to show that diet drugs reduce the risk of premature death or illness associated with long-term obesity and inactivity. Moreover, they are associated with serious adverse effects.

Orlistat (XENICAL) was approved by the Food and Drug Administration (FDA) in 1999 as a prescription drug at a dose of 120 milligrams (mg) up to three times daily for inducing weight loss in obese patients in conjunction with a reduced-calorie diet.[6] It also is now approved to reduce the risk for regaining weight after prior weight loss. The over-the-counter form, ALLI, which contains half of the orlistat dose of Xenical (60 mg), was approved in 2007.[7] Unlike most other weight loss drugs that work by either suppressing appetite or increasing satiety (the feeling of fullness), orlistat prevents the breakdown and absorption of fat from ingested foods in the gastrointestinal tract; in this manner, fat absorption is decreased by approximately 30%.[8] A dose of the drug is to be taken with each meal containing fat up to three times daily.

We have classified orlistat as Do Not Use because the risk of serious adverse events greatly outweighs its meager benefits.

Minimal benefit

Clinical trials testing orlistat demonstrated that the weight loss seen in subjects treated with the drug was minimal. For example, one trial showed that obese subjects taking Xenical in combination with dieting and exercise for one year lost only an additional 5.6 pounds with the 60-mg dose and 7.1 pounds with the 120-mg dose compared with subjects who took a placebo.[9]

Similarly, the FDA statistician who reviewed the trials on Alli concluded that overweight users can expect to lose only two to four more pounds than those who rely solely on diet and exercise routines to lose weight.[10]

Given these results, Public Citizen’s Health Research Group testified before an FDA advisory committee urging against the approval of this drug because it has not been shown to confer a health benefit, as the FDA-approved product label states: “The long-term effects of orlistat on morbidity and mortality associated with obesity have not been established.”

Dangerous adverse effects

In addition to its limited effectiveness in inducing weight loss, orlistat poses unacceptable risks. For example, there is evidence that use of the drug is associated with an increased risk of cancer. In fact, orlistat’s approval was delayed because in seven randomized clinical trials, there were ten cases of breast cancer in women taking the drug and only one case in women taking a placebo.[11] In addition, animal studies submitted to the FDA prior to approval showed that orlistat can cause precancerous changes in the colons of rats. A large body of research has demonstrated that these precancerous lesions can be precursors to developing cancer. In 2006, we petitioned the FDA to immediately remove Xenical from the market primarily because of the precancerous changes observed in rats,[12] but the agency denied our petition in 2007.[13]

Another serious adverse event associated with this drug is severe liver injury or failure resulting in liver transplantation or death. In August 2009, the FDA announced it was reviewing safety information regarding reports of liver-related adverse events in patients taking orlistat.[14] The final review identified 13 cases of severe liver injury. Twelve of these cases were reported with the use of the 120-mg orlistat dose and one was reported with the use of the 60-mg product. In some of these cases, other factors or drugs may have contributed to the development of severe liver injury. Of the 13 cases, two patients died from liver failure, and three patients required liver transplants.[15] In 2010, the FDA issued another warning about “severe liver injury” rarely being reported in patients using orlistat.

Orlistat also has been associated with acute pancreatitis (inflammation of the pancreas, which can cause severe abdominal pain, nausea and vomiting) and kidney stones. Our review of FDA MedWatch adverse reaction reports in 2011 found 47 cases of pancreatitis associated with Xenical or Alli. Thirty-nine of those patients required hospitalization and one died. We also identified 73 cases of kidney stones associated with Xenical or Alli use, of which 23 required hospitalization. These findings supported our second petition filed in April 2011 urging the FDA to immediately ban orlistat because it exposes patients to serious risks.[16] However, the FDA again rejected our petition in 2013.[17]

Other less serious but common adverse effects of orlistat include gallstones, abdominal pain, gas, fecal urgency and oily stools. Orlistat interferes with the absorption of fat-soluble vitamins (A, D, E and K), so patients are instructed to take supplements that contain these vitamins. It also interacts with commonly used medications.[18]

Taken together, the evidence demonstrates that orlistat is a dangerous drug that does not significantly improve weight loss and can lead to serious detrimental health effects and even death.

What You Can Do

If you are one of the millions of Americans who are overweight or obese, you should never take orlistat to lose weight. Likewise, do not fall victim to any other weight-loss drugs on the market. Instead, follow the only effective and safe long-term solution for shedding any unwanted pounds: regular exercise and a lower-calorie diet.
 



References

[1] World Health Organization. Nutrition: Controlling the global obesity epidemic. WHO. https://www.who.int/nutrition/topics/obesity/en/. Accessed September 9, 2019.

[2] Centers for Disease Control and Prevention. Obesity and overweight. August 13, 2018. https://www.cdc.gov/nchs/fastats/obesity-overweight.htm. Accessed September 10, 2019.

[3] Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. 2012;42(6):563-570.

[4] Centers for Disease Control and Prevention. About adult BMI. August 29, 2017. https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/index.html. Accessed September 10, 2019.

[5] Centers for Disease Control and Prevention. Adult obesity causes and consequences. August 29, 2017. https://www.cdc.gov/obesity/adult/causes.html. Accessed September 10, 2019.

[6] CHEPLAPHARM Arzneimittel GmbH. Label: orlistat (XENICAL). January, 2018. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6240792b-9224-2d10-e053-2a91aa0a2c3e&type=display. Accessed September 10, 2019.

[7] GlaxoSmithKline Consumer Healthcare Holdings. Label: orlistat (ALLI). April 2018. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f&type=display. Accessed September 10, 2019.

[8] CHEPLAPHARM Arzneimittel GmbH. Label: orlistat (XENICAL). January, 2018. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6240792b-9224-2d10-e053-2a91aa0a2c3e&type=display. Accessed September 10, 2019.

[9] FDA should remove weight-loss drugs ALLI and XENICAL from the market. Worst Pills, Best Pills News. October, 2011. /newsletters/view/768. Accessed September 10, 2019.

[10] Ibid.

[11] Public Citizen asks FDA to immediately remove orlistat (XENICAL) from the market. Worst Pills, Best Pills News. June 2006. /newsletters/view/466. Accessed September 10, 2019.

[12] Public Citizen. Petition to ban diet drug orlistat (Xenical). Citizen. April 10, 2006. https://www.citizen.org/article/petition-to-ban-diet-drug-orlistat-xenical/. Accessed September 10, 2019.

[13] Food and Drug Administration. Petition denial letter to Public Citizen. February 7, 2007. https://www.regulations.gov/document?D=FDA-2006-P-0326-0002. Accessed September 10, 2019.

[14] Food and Drug Administration. Early communication about an ongoing safety review of orlistat (marketed as Alli and Xenical). August 24, 2009. http://wayback.archive-it.org/7993/20170112182231/http:/www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm179166.htm. Accessed September 10, 2019.

[15] Food and Drug Administration. FDA drug safety communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury. May 26, 2010. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-completed-safety-review-xenicalalli-orlistat-and-severe-liver-injury. Accessed September 10, 2019.

[16] Public Citizen. Petition to FDA to ban orlistat (Alli, Xenical). Citizen. April 14, 2011. https://www.citizen.org/wp-content/uploads/migration/1942.pdf. Accessed September 9, 2019.

[17] Food and Drug Administration. Petition denial letter to Public Citizen. December 16, 2013. https://www.citizen.org/wp-content/uploads/1942_fda_response_to_orlistat_petition_denial.pdf. Accessed September 10, 2019.

[18] CHEPLAPHARM Arzneimittel GmbH. Label: orlistat (XENICAL). January, 2018. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6240792b-9224-2d10-e053-2a91aa0a2c3e&type=display. Accessed September 10, 2019.