Side Effects of Alli (Orlistat) for Weight Loss
The most common side effects of Alli are gastrointestinal—specifically oily spotting, loose stools, flatulence, and fecal urgency/incontinence—which occur nearly 3 times more frequently than placebo and are the primary reason patients discontinue the medication. 1
Common Gastrointestinal Side Effects
The gastrointestinal effects are directly related to orlistat's mechanism of blocking approximately 30% of dietary fat absorption: 2, 3
- Gas with oily spotting - fat passes through undigested 2
- Loose, more frequent stools that may be difficult to control 2
- Oily/fatty stools and fecal urgency 1
- Flatulence 1, 3
These effects are most pronounced when eating high-fat meals and typically occur early in treatment, often decreasing with continued use. 4 Following a low-fat diet (approximately 30% of calories from fat) significantly reduces the likelihood and severity of these symptoms. 5, 2
Serious but Rare Side Effects
Liver Injury (FDA Warning)
The FDA has issued a specific warning about potential serious liver injury with orlistat. 1, 5, 2 There have been 13 documented cases of liver failure (12 cases with the 120mg prescription dose, 1 case with the 60mg over-the-counter dose). 1
Stop the medication immediately and seek medical attention if you develop: 2
- Itching
- Yellow eyes or skin (jaundice)
- Dark urine
- Loss of appetite
Other Serious Concerns
- Severe or continuous abdominal pain may indicate a serious condition like pancreatitis and requires immediate medical evaluation 2
- Cholelithiasis (gallstones) - small increased risk associated with weight loss on orlistat 1
- Kidney stones - patients with a history should consult a physician before use 2
Nutritional Deficiencies
Because orlistat blocks fat absorption, it also reduces absorption of fat-soluble vitamins (A, D, E, K): 1, 5, 2
- Mandatory daily multivitamin supplementation is required 1, 5
- Take the multivitamin at least 2 hours apart from orlistat (ideally at bedtime) 5, 2
- Vitamin D and beta-carotene levels may decrease but typically remain within normal range 3
Drug Interactions Requiring Monitoring
Certain medications require dose adjustments or closer monitoring when taken with orlistat: 1, 5
- Cyclosporine - contraindicated; do not use together (or separate by at least 3 hours) 5, 2
- Levothyroxine - may require dose adjustment and longer dosing intervals 1, 5
- Warfarin - requires closer INR monitoring 1, 5
- Antiretrovirals (HIV medications) - may be affected 2
- Seizure medications - monitor for increased seizure frequency 2
Treatment Discontinuation Rates
The side effect burden is substantial enough that: 1
- Patients are 1.51 times more likely to discontinue treatment due to adverse effects compared to placebo 1
- Specifically for GI side effects, discontinuation is 2.86 times higher than placebo 1, 5
Who Should NOT Use Orlistat
Absolute contraindications: 2
- Organ transplant recipients
- Allergy to orlistat ingredients
- Chronic malabsorption syndrome 1, 2
- Cholestasis 5
- Pregnancy or breastfeeding 2
Use caution or avoid if you have: 2
- History of gallbladder problems
- Kidney stones
- Pancreatitis
- Chronic diarrhea, celiac disease, inflammatory bowel disease, or prior bariatric surgery 1
Clinical Context
The 2022 American Gastroenterological Association guidelines actually make a conditional recommendation AGAINST routine orlistat use due to the modest weight loss benefit (only 2.8 kg more than placebo) balanced against the high rate of bothersome GI side effects. 1, 5 However, patients who highly value even modest weight loss and can tolerate GI effects may reasonably choose it. 1