Orlistat experiences almost all revolve around the same thing: it works modestly, and the bowel complaints decide whether you stick with it. Orlistat blocks roughly 30% of the fat in your food, which then leaves the body undigested.
That last part is exactly as unpleasant as it sounds.
What appears almost nowhere is that the drug blocks not only fat but also the vitamins dissolved in it. That makes orlistat the one weight-loss drug where a vitamin deficiency is a predictable consequence rather than a coincidence.
How does orlistat work?
It inhibits lipase, the enzyme that breaks fat down in the gut into a form your body can absorb. What is not broken down is not absorbed and leaves the body in the stool. At the usual dose that means roughly a third of the fat in your meal.
The drug therefore works in the gut, not in the brain.
That is the fundamental difference from the GLP-1 drugs and from Mysimba. Those dampen hunger; orlistat leaves your hunger entirely intact and removes some of the calories afterwards.
In the Netherlands orlistat is sold as Xenical (120 mg on prescription) and as Alli (60 mg, a lower dose). The Dutch Farmacotherapeutisch Kompas describes dosing three times daily with a fat-containing meal.
How much weight do you lose with orlistat?
Modestly, but demonstrably and over a long follow-up. In the XENDOS trial, with 3,305 participants over four years, users lost an average of 5.8 kilos against 3.0 kilos on placebo. More importantly, the chance of developing type 2 diabetes fell from 9.0% to 6.2%, a risk reduction of 37.3% (Torgerson et al., 2004).
Four years of data is more than the newer drugs can show.
The weight loss itself stays small by comparison. Naltrexone with bupropion reached 6.1% in COR-I (Greenway et al., 2010) and liraglutide 8.4 kilos in SCALE (Pi-Sunyer et al., 2015).
| Drug | Where it acts | Average loss in trials | Most cited complaint |
|---|---|---|---|
| Orlistat | Gut, blocks fat absorption | 5.8 kg over 4 years | Oily, unpredictable stool |
| Naltrexone and bupropion | Brain, reward system | 6.1% over 56 weeks | Nausea and poor sleep |
| Liraglutide | Brain and stomach, hunger signal | 8.4 kg over 56 weeks | Nausea |
| Semaglutide | Brain and stomach, hunger signal | 14.9% over 68 weeks | Nausea |
| Tirzepatide | Brain and stomach, two hormone routes | 20.9% over 72 weeks | Nausea |
These drugs were not compared head to head in one trial, so read these rows as orders of magnitude rather than a ranking.
Which side effects do users report?
Almost exclusively bowel complaints, and they are directly tied to what you eat. Users report oily stool, sudden urgency, oily spotting and flatulence. The more fat in the meal, the more severe the complaints.
That makes orlistat the one weight-loss drug with a built-in correction.
Eat too much fat and you find out the same day. Some users call that the real active ingredient, and there is something to that, even if it is not a pleasant way to learn it.
The Dutch Voedingscentrum advises spreading fat intake across the day as part of a healthy eating pattern, which with this drug also limits the complaints.
Which blood values are relevant with orlistat?
The fat-soluble vitamins, because that is the logical flip side of the mechanism. Vitamins A, D, E and K are absorbed together with fat, so if some of the fat is not absorbed, neither are those vitamins. Vitamin D is the one that matters most in the Netherlands, because the baseline level here is already low in winter.
That connection is drawn on almost no Dutch experience page.
Alongside it, ferritin is worth knowing during long-term use combined with eating less, because iron stores drift slowly with a lower intake.
Our GLP-1 extended check contains the vitamin values alongside the metabolic picture, assessed by a BIG-registered doctor. The name refers to the journey, not the drug.
Who is orlistat a reasonable choice for?
For people who do not want or cannot get injections, and who have a fat-rich eating pattern where there is still ground to gain. For someone who already eats little fat there is little to block and the effect stays small. Your GP can judge whether it fits your eating pattern.
The other options sit side by side in weight-loss medication, and the other tablet drug is covered in Mysimba experiences.
What strikes me about orlistat is that it is the most honest drug of the set. It promises little and delivers exactly that.
If you use it for longer than a few months, have your vitamin D determined before a deficiency shows up as fatigue.
References
- Torgerson JS et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study. Diabetes Care. 2004. PMID 14693982
- Greenway FL et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I). Lancet. 2010. PMID 20673995
- Pi-Sunyer X et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015. PMID 26132939
- Farmacotherapeutisch Kompas, monograph for orlistat (dosing and mechanism).
- Voedingscentrum, information on fats in a healthy eating pattern.
Every blood test result includes a professional assessment from a BIG-registered doctor. For treatment decisions, discuss your results with your GP.
Autor
SlimmerLab
Dr. Naimi, lekarz wpisany do holenderskiego rejestru BIG, nadzoruje standardy medyczne naszych treści i ocen. Przeczytaj naszą politykę medyczną