Disclaimer: None of the information in this article constitutes medical advice, and is just the opinion of the writer(s) and published for informational purposes only. We recommend that patients follow their doctor’s guidance in regard to prescription medication.
Orlistat is a weight loss pill that’s approved by the Food and Drug Administration (FDA) in the U.S. It’s one of the only over-the-counter (OTC) weight loss medications approved by the FDA, meaning that it doesn’t require a prescription from a doctor.
Orlistat is the generic name for the medication, and the brand-name version is Alli. We will use these terms interchangeably throughout this article because they refer to the same active chemical compound.
In this article we’ll review published medical studies on orlistat to determine if it’s safe and effective for weight loss. We’ll explain the side effects of the medication, review whether the generic or brand-name version is more likely to be effective, and share information about a few natural weight loss options.
Does Orlistat Work?
Orlistat has been proven successful for weight loss in numerous medical trials, as is required for FDA approval.
A clinical trial published in the Journal of the Academy of Nutrition and Dietetics tested orlistat for weight loss in a population of overweight U.S. soldiers. The study participants used 60 milligrams (mg) capsules of orlistat (which is the same dosage as contained in Alli) three times daily, totalling a 180 mg dose per day.
By the end of the six month trial, the soldiers taking orlistat had lost 1.3 kilograms (kg) of fat more than those taking placebo pills, which is equivalent to 2.87 pounds (lbs). It’s worth noting that the soldiers weren’t obese, but they were slightly overweight (greater than 2% above the percent body fat standard).
While this trial did show orlistat may be effective, we don’t find the results to be very impressive. An average weight loss of 0.5 lb per month may not be worth the risk of pharmaceutical side effects in our opinion. This level of weight loss is easily achievable through dietary modifications.
A separate clinical trial on orlistat, published in 2012, reported more impressive results. This study included both overweight and obese patients who took orlistat 60 mg capsules three times daily for 24 weeks along with diet and exercise counseling. The patients using orlistat lost 15.7% of visceral fat (fat around organs) compared to visceral fat loss of 9.4% for patients taking placebo pills.
Those using orlistat lost an average of 10.25 lbs of fat overall, which is significant.
Orlistat has also been proven effective for patients who are only slightly overweight. A medical study published in 2006 examined the effects of 16 weeks of orlistat for patients who were categorized as “mildly to moderately overweight.” The dosage was 60 mg, three times per day which seems to be the research standard.
Patients in this trial were assigned to a restricted calorie diet supplemented with either orlistat or a placebo pill. Both groups lost weight, but the group taking orlistat lost 2.54 lbs more, which if sustained would equate to an annual weight loss of 8.26 lbs more than using diet alone.
We will conclude from the available research that orlistat is effective for weight loss, and appears to be more effective for patients at a higher starting weight such as obese patients.
Is Orlistat 120 mg More Effective?
All of the research reviewed in the previous section utilized orlistat 60 mg per tablet, but the drug can also be prescribed at a dosage of 120 mg per tablet. The branded version of orlistat 120 mg is called Xenical, and is only available with a prescription.
Patients are often curious about whether the higher orlistat dosage is more effective for weight loss.
While we cannot locate any medical studies directly comparing the weight loss outcomes of orlistat 60 mg versus orlistat 120 mg per tablet, this medical review reported that the drug has dose-dependent effects on weight. This means that the higher the dose, the more weight is lost on average, which would suggest that orlistat 120 mg is more effective for weight loss than orlistat 60 mg. The researchers in the linked review concluded that orlistat 120 mg “represents the optimal dosage regimen.”
Since higher doses of pharmaceutical drugs tend to be associated with higher risk of side effects, it may be worthwhile for patients considering orlistat to start at the 60 mg dose, and only increase the dose if the starting dose is ineffective, but only a doctor can provide individualized dosage advice.
How Does Orlistat Work?
We believe it’s important for patients to understand the mechanism of action of their medications, so they can notice trends about types of drugs that are effective or ineffective for their individual biochemistry.
Orlistat’s mechanism of action is to inhibit the production of certain proteins that break down fat consumed in the diet, as documented by StatPearls, which is one of the largest free medical databases in the U.S.
Patients taking orlistat excrete more fat in feces than they would otherwise, which results in a lower percentage of fat being absorbed and metabolized by the body. The StatPearls resource reports that around 30% less dietary fat is absorbed on orlistat than would be otherwise.
These effects are reversible, and when a patient stops taking orlistat their pancreatic and gastric proteins return to functioning as normal.
Orlistat Side Effects
The more common side effects of orlistat are relatively mild, but there is a small risk of severe side effects.
The most common side effect as reported by the previously-linked StatPearls database is oily stool (medical term “steatorrhea”), but this should be expected because the drug increases the excretion percentage of dietary fats.
A meta-study of orlistat reports that patients who keep dietary fat intake under 60 grams (g) daily experience fewer gastrointestinal side effects such as diarrhea and abdominal pain.
The same study documents that there is a rare risk of acute kidney injury because orlistat can increase oxalate production, which is deposited in the kidneys.
The FDA has also reported that orlistat is associated with a small but increased risk of severe liver injury. Only 13 out of over 40 million patients reported experiencing this side effect.
The side effect profile of orlistat is relatively mild compared to some of the pharmaceutical drugs we’ve reviewed on Illuminate Health. The drug does not appear to carry a “black box” warning on its FDA label, which is required for medications with severe or life-threatening side effects.
Natural Weight Loss Options
There exist some natural weight loss options backed by significant medical research that patients may want to consider. These compounds are available OTC and may confer a lower risk of side effects than orlistat.
We’re not suggesting that these compounds are as effective as orlistat; just that they may be a healthier option long-term.
Regular caffeine intake has been associated in medical trials with reduced weight. A medical review on caffeine and weight loss analyzed data from 13 clinical trials and found that for every doubling in caffeine intake, weight loss increased. The average weight loss reported was around 4 lbs over 4 weeks, which if sustained would equate to an annual weight loss of around 52 lbs.
Caffeine intake isn’t safe for all patients, and likely should be avoided by patients with high blood pressure because it’s a stimulant, so we recommend that patients speak with their doctor prior to taking caffeine for weight loss.
We believe that consuming black coffee is a healthier and safer option for caffeine intake than caffeine pills. Coffee consumption has been associated with reduced all-cause and cancer mortality in medical research, and there’s a much lower risk of accidentally ingesting too high of a dose with coffee when compared with pills.
Caffeine is effective as a weight loss aid because it’s a mild stimulant which increases base metabolic rate and decreases appetite. It’s generally a good idea to drink black coffee in the morning so it doesn’t interfere with sleep.
Increased dietary fiber consumption is also proven to cause weight loss, and this is the most well-studied natural weight loss option in our opinion. Increasing dietary fiber intake delays gastric emptying and increases the sense of fullness, which allows for calorie restriction without the cravings that are common in commercial diet plans.
The Journal of Nutrition published a meta-review in 2019 detailing how fiber intake predicts weight loss in adults. The vast majority of American adults don’t get enough fiber daily, because foods rich in fiber like beans and starchy grains aren’t part of the Standard American Diet.
The average fiber intake in the study was 25.2 grams (g) per day. This can be achieved by eating high-fiber foods like raw vegetables, or by supplementation with fiber powder that contains no filler ingredients like added sugar.
Orlistat User Reviews
Orlistat has been reviewed over 300 times on Drugs.com, which is a website where users of pharmaceutical medication can publish reviews of their experience.
We cannot verify the accuracy or authenticity of any information on this site, but we still find some of the insights valuable since it’s the largest hub of user medication reviews.
Orlistat has an average rating of 7.3/10 for treating obesity on Drugs.com, which is one of the higher average ratings we’ve noted.
The top positive review of the drug is written by a used named “Gurlo” who claims the drug was successful for their weight loss goal even without incorporating exercise:
“25, female, started off at 15st 7lbs or 99kg or 217lbs (I’m 5’7). Originally was looking for a quick fix but realistically when it comes to weight loss there isn’t one. I gained 70lbs in the last 4 years and finally realized how unhappy I was. 20 days in and I have lost 14lbs/6kg. I am strict on my diet, though to be honest haven’t done the recommended exercise. So I can only imagine how much I would have lost in that time.”
The top negative review is published by a user named “FairyGardens” who rated the drug 1/10 and claims it was ineffective:
“The new generation of Orlistat, sold over the counter as Alli, does NOT work. I was on Xenical when it first came out in the 1990's. It worked very well and the orange discharge was a daily thing. Now 4 months ago I purchased Alli over the counter. Paid $85 and was very disappointed to find out that I had wasted my money.”
Should I Take the Branded Version of Orlistat?
As we’ve referenced multiple times throughout this article, orlistat is the term for the generic version of the drug and the brand-name versions are Alli and Xenical. Alli is the 60 mg OTC version and Xenical is the 120 mg prescription version.
We generally recommend that patients speak with their doctor about the generic form of pharmaceutical drugs, because they’re just as effective as branded drugs but cheaper.
A medical review published in the PLOS Medicine journal compared the efficacy of generic and branded drugs, and found that there was no difference: “use of generics was associated with comparable clinical outcomes to use of brand-name products.”
Generic orlistat doesn’t appear to be available, at least in the U.S., but we would recommend that international patients who can access this medication speak with their doctor about it rather than Alli or Xenical.
