Orlistat is the active ingredient in clinically tested and highly successful weight loss medication, available in both prescription form as Xenical, and over-the-counter form as Alli. As of writing this text, Orlistat is the only weight loss drug approved by European Medicines Agency and its discovery is widely considered as a major development in the fields of obesity treatment and management. With reliable and noticeable, yet somewhat modest results, Orlistat remains the only weight loss pill proven to produce consistent results when used in conjunction with individualized lifestyle changes recommended by experts such as exercise and diet plans. In its 120mg form, Orlistat is prescribed by doctors to patients with body mass index greater than 30 or when obesity-related conditions such as high blood pressure, cholesterol or diabetes pose a significant risk to the health of the individual, while 60mg less concentrated form can be purchased over-the-counter and used for moderate weight loss, mostly due to aesthetical considerations.

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However, in both forms, Orlistat is known for its side effects, which are localized to gastrointestinal adverse effects but can get rather unpleasant, leading to the termination of treatment in up to 8.8% of patients, as shown by double-blind clinical tests. While they manifest in up to 50% of patients, Orlistat side effects usually last between one and four weeks since the beginning of the treatment and can be successfully managed in most cases with the appropriate dietary regime.

Orlistat side effects and contraindications

Orlistat contraindications

In some cases, Orlistat treatment should be avoided, most notably during pregnancy or in patients with chronic malabsorption syndrome, cholestasis or known hypersensitivity to Orlistat. The identification of secondary medical conditions, unrelated to obesity is one of the most important reasons why consultations with the doctors are highly recommended.

Due to its unique mechanism of action, another identified Orlistat side effect is reduced absorption of some fat-soluble vitamins and beta-carotene which leads to a deficit in these nutrients, crucial for the healthy and unimpeded functioning of the human organism. This is why it is advisable that the patients take a multivitamin tablet containing vitamins A, D, E, K and beta-carotene once a day, before bed, to make up for the deficit in these nutrients.

Drug interactions

When it comes to Orlistat side effects which are the result of drug interactions there have been only a few identified cases, most importantly those related to cyclosporine and levothyroxine. For patients receiving cyclosporine therapy, it should be administered 3 hours or more after Orlistat dose, which should be enough to mitigate all potential interactions. When it comes to levothyroxine, the time between doses should be even greater, with a recommendation that the two are administered at least 4 hours apart. However, even then, it is advisable that thyroid functions are closely monitored, at least in the first couple of weeks of treatment, to ensure no Orlistat side effects related to this function are manifested. It is worth noting that this risk is present only for patients who are receiving levothyroxine therapy and have not been recorded otherwise.

Common side effects

Most common Orilstat side effects, shared with branded version Xenical, are localized to the gastrointestinal adverse effects and manifest in roughly 50% of the patients. The following table illustrates the average percentage of patients in clinical trials that experienced the symptoms in the first three months of treatment compared to the percentage of patients who were taking placebo over the same period. It’s important to note that both those receiving Orlistat treatment and those receiving placebo also got personalized diet plans to accompany treatment. The study confirmed known Orlistat side effects while also providing valuable information about the prevalence of these symptoms and the possibility of them being caused by other factors, such as sudden changes to the dietary regime. It is also important to note that this can explain certain discrepancies between orlistat and over-the-counter Alli side effects.

Adverse Effect Patients on Orlistat Patients on Placebo
Oily Spotting 26.6% 1.3%
Flatulence 23.9% 1.4%
Fecal Urgency 22.1% 6.7%
Fatty/Oily Stool 20% 2.9%
Oily Evacuation 11.9% 0.8%
Increased Defecation 10.8% 4.1%
Fecal Incontinence 7.7% 0.9%

Rare side effects

Rarer Orlistat side effects are usually unrelated to gastrointestinal functions and processes, and they are not as well-known as the more common ones, mostly due to the fact that that there is relatively little data to ensure reliable results. Reports of some of the more severe Orlistat side effects, such as liver injury, have been thoroughly examined by medical experts, yet the results disproved the original claims of those side effects. Indications that liver injuries were more common in patients taking Orlistat than in those who don’t were met with concern by the experts, so numerous clinical tests were organized, resulting in the examination of more than 94.000 patients taking Orlistat. After the study was concluded, the scientific team found no evidence of increased risk of liver injury or any Orlistat side effects manifested in the change of liver functions or health.1

On the other hand, a study far smaller in scale, conducted in Canada showed that another rare Orlistat side effect is increased risk of acute kidney injury. It was argued that Orlistat’s unique mechanism of action leads to excessive oxalate absorption from the gut and its subsequent deposition in the kidney, with excessiveness of oxalate being a known consequence of medical conditions that cause fat malabsorption, something which is also at the core of Orlistat’s mechanism of action. However, while there are some indications this might be the case, there is still insufficient evidence for any definitive conclusion to be drawn. What’s more, if this proves to be a real Orlistat side effect, there is a possibility that, similar to vitamin deficit and other gastrointestinal effects, it can be mitigated with proper diet, supplements or additional therapy.

Side effects: Conclusion

With all this in mind, one question remains – do the benefits outweigh the risks or is it the other way around? Is Orlistat therapy worth it?

In many cases, where the 120mg form is prescribed, Orlistat is the weight loss drug that truly made a difference in people’s lives, helping them lead healthier lives while significantly reducing the risks of obesity-related diseases. Here, the answer is clear – even though Orlistat side effects can be rather unpleasant, the results of the therapy were reliable, noticeable and significant


  1. Orlistat and the Risk of Acute Liver Injury – the BMJ