Alli: The FDA’s First Over-the-Counter Diet Drug


Alli is the first FDA-approved over-the-counter weight loss pill. Made by GlaxoSmithKline, Alli is a half-dose version of the prescription drug Xenical. Orlistat, the active ingredient in both Xenical and Alli, inhibits the absorption of certain fats in the intestine.[1] The subsequent excretion of these unabsorbed fats helps patients lose weight. While Xenical is sold in 120 mg doses and usually taken 3 times per day, Alli pills are 60 mg each and are taken 3 times daily with each fat-containing meal.

For the drug to be fully effective, the “myAlliplan” recommends starting a diet prior to taking Alli. The plan specifies that the drug is to be used only in conjunction with a weight loss program that includes a reduced calorie diet, a low fat diet, and an exercise program.[2]

FDA Approval and Known Side Effects

Alli is approved for overweight or obese adults over 18 years of age and is not intended for people who have problems absorbing food or for those who are not overweight. If someone is taking blood thinning medications or is being treated for diabetes or thyroid disease, physician consultation is recommended.[3]

The most common side effects of orlistat include “oily spotting, loose stools, more frequent stools that may be hard to control,” and flatulence.[4] Suggestions provided by GlaxoSmithKline’s myalli.com Web site include wearing dark pants and remaining near a bathroom. The Web site also suggests strictly following the low-fat, low-calorie diet and regular exercise recommended for Alli users in order to minimize such side effects. By consuming fewer calories and burning more fat through exercise, overall fat levels in the body drop and therefore less fat passes through the digestive system.

Does it Work?

The side effects are much worse if a patient eats fats in their diet, so people taking orlistat will be highly motivated to eat a low-fat diet. Perhaps for this reason, clinical trials indicate that orlistat users are more likely to lose at least 5% of their baseline weight compared to other dieters, and although they often gain the weight back they keep off more weight compared to other dieters.[5, 6] Diabetics who take orlistat have lower blood sugar levels and blood pressure than other diabetics, but their weight loss is modest.[7] Some experts question whether the benefits outweigh the side effects and risks: for example, in one recent study, the orlistat + diet and exercise group went from 242 lbs to 229 lbs and the placebo + diet and exercise group went from 242 lbs to 235 lbs.[8] These are modest weight losses, and the orlistat dosage in that study was twice as high as Alli’s.

Alli blocks about 25 percent of the fat a person consumes from being absorbed by the intestine so that the excess fat passes through the system.[19] The absorption of fat-soluble minerals and vitamins such as E, A, D, and K is also partially inhibited, but patients in clinical trials did not suffer from vitamin deficiency if they consumed vitamin supplements concurrently with orlistat.[10]

What are the Risks?

Other than the previously mentioned gastrointestinal side effects and loss of vitamins, there are concerns that orlistat may cause colon and breast cancer. Public Citizen Health Research Group raised these concerns to the FDA in a citizen petition demanding the removal of Xenical from the market and the denial of approval for Alli.[11] They pointed out that previous studies found a significant increase in breast cancer among orlistat users, and evidence that these drugs cause a significant increase in aberrant crypt foci, which research indicates could be a “precursor of color cancer.” In their response to the petition, the FDA did not deny that there were unanswered questions about long-term safety, but indicated that the evidence was not sufficient to justify rescinding approval.[12] The FDA maintains that orlistat is safe and effective.[13] However, the lack of long-term data raises questions about long-term safety.

In summary, Alli can help people stick to their diets, because cheating can cause very unpleasant gastro-intestinal side effects. As a result, Alli + diet + exercise seem to be more effective than diet + exercise alone. However, most people who take Alli or Xenical do not lose 5% of their weight or more (10 pounds for someone starting at 200 pounds), many of those taking the drug may need to stay close to a bathroom to avoid embarrassment, and the drug could potentially increase the risk of breast cancer or colon cancer in the long-term.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References

1. Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB. “Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial.” JAMA 281(3):235-42. 1999

2. MyAlli.com, “Preparing for Alli” Accessed  August 2010. Available: http://www.myalli.com/Getting_Started/Preparing_for_alli.aspx

3. “FDA Approves Orlistat for Over-the-Counter Use,” Food and Drug Administration Press Release. 7 February 2007.

4. MyAlli.com, “How Does it Work – Treatment Effects,” Accessed August 2010. Available: http://www.myalli.com/About_alli/treatment_effects.aspx

5. Galson, Steven K., Letter in response to citizen petition to FDA on 10 April 2006., Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD. 07 February 2007. page 24

6. Kelley et al, “Clinical Efficacy of Orlistat Therapy in Overweight and Obese Patients with Insulin-Treated Type 2 Diabetes,” Diabetes Care, Vol 25 No. 6:1033-1041, 06 June 2002

7. Kelley et al, “Clinical Efficacy of Orlistat Therapy in Overweight and Obese Patients with Insulin-Treated Type 2 Diabetes,” Diabetes Care, Vol 25 No. 6:1033-1041, 06 June 2002

8. Public Citizen Petition to the FDA to immediately remove the diet drug orlistat (XENICAL) from the market (HRG Publication #1764) April 10, 2006 available at http://www.citizen.org/publications/release.cfm?ID=7423#_ftnref34

9. Squires, Sally, “Lowdown on OTC Weight-loss Drug,” The Washington Post. 20 February 2007.

10. Chanoine, JP, Hampl, S, Jensen, C, Boldrin, M, Hauptman, J. “Effect of Orlistat on weight and body composition in obese adolescents.” JAMA 293, 23: 2873-2883. 2007

11. Barbehenn, Elizabeth; Sidney Wolfe; Theresa P. Pretlow; Thomas G. Pretlow. Citizen petition to remove prescription orlistat from the market. Public Citizen Health Research Group. 10 April 2006.

12. Galson, Steven K., Letter in response to citizen petition to FDA on 10 April 2006., Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD. 07 February 2007. pages 5-8, 11, 12, 15, 18, 20

13. Galson, Steven K., Letter in response to citizen petition to FDA on 10 April 2006., Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD. 07 February 2007. pages 6, 7, 11-13