If you’ve been taking Orlistat for some months and are wondering if it’s having any hidden side effects, here’s a straightforward answer, based on what the long-term evidence really says, and what warning signs should make you contact your GP in the UK.
Key Facts:
Orlistat has 4 years of clinical trial safety data from the XENDOS study (4), with no major increases in serious adverse events versus placebo.
MHRA has received reports of rare hepatitis and rare oxalate nephropathy (fewer than 1 in 1,000) (2). Look out for signs of jaundice, dark urine, pale stools or unexplained fatigue.
NICE says Orlistat should only be continued past 3 months if you have lost at least 5% of your starting body weight (1).
Take a once-daily multivitamin containing vitamins A, D, E and K at least 2 hours before or after taking Orlistat or at bedtime (3).
Clinically relevant long-term interactions exist with ciclosporin, levothyroxine, antiepileptics, warfarin and the combined oral contraceptive pill (2)(3).
In this article:
Is long-term Orlistat safe?
A safety timeline: what to watch for at 3, 6, 12 and 24+ months
Does long-term Orlistat cause liver damage?
Can Orlistat cause kidney stones or kidney problems long-term?
Do I need a multivitamin on Orlistat, and when should I take it?
Does long-term Orlistat interact with other common UK medications?
Does long-term Orlistat affect my bowel health?
What should I discuss with a UK prescriber at a long-term review?
Frequently asked questions about long-term Orlistat
Is long-term Orlistat safe?
Long-term Orlistat is well-tolerated in most adults. The XENDOS clinical trial, which was conducted over 4 years, didn't show a particularly high number of serious issues, although signs of liver and kidney problems, which are unusual, do need to be looked out for (4).
Orlistat has one of the longest safety records of any UK-licensed weight-loss medicine. The XENDOS clinical trial followed 3,305 adults over 4 years and it discovered that gastrointestinal issues were most common in the first year but there wasn't a significant increase in serious side effects over and above those experienced by people on the placebo (4).
There are two things to bear in mind. Firstly, the NICE guidance NG246 states that Orlistat should only be continued after 3 months if you’ve managed to lose at least 5% of your original weight (1). Secondly, very serious incidents including hepatitis and oxalate nephropathy have been reported to the Medicines and Healthcare products Regulatory Agency (MHRA) (2) and require careful monitoring.
In summary, most people can continue with Orlistat for between 12 and 24 months without problems as long as they correctly take a multivitamin, drink enough water and have a yearly check-up with their doctor.
A safety timeline: what to watch for at 3, 6, 12 and 24+ months
The side effects of Orlistat may behave differently depending on how long you’ve been on the medication. You can use this timeline as a quick reference guide.
Time point | What typically happens | What to do |
|---|---|---|
Month 0 to 3 | Bowel effects are at their peak: oily stools, urgency, flatulence | Follow the NICE 5% rule (1): stop at month 3 if weight loss is below 5% of starting weight |
Month 3 to 6 | Bowel symptoms settle as diet adapts. Fat-soluble vitamin levels may start to dip | Take a once-daily multivitamin (A, D, E, K) at bedtime |
Month 6 to 12 | Rare liver injury cases have been reported in this period (2)(3) | Red flags: jaundice, dark urine, pale stools, unexplained fatigue, right-upper-quadrant pain. Stop and see a doctor as soon as you can |
Month 12 to 24 | Long-term vitamin D and K levels may become an issue. Bone and bleeding signs become more relevant | Ask your GP for an annual vitamin D blood test. Warfarin users: INR monitoring remains essential |
Month 24+ | Ongoing review recommended | Periodic liver function tests and vitamin level tests. Discuss with a UK prescriber whether Orlistat is still the right fit for you |
Does long-term Orlistat cause liver damage?
Although not common, serious liver problems have been reported with Orlistat. If you develop jaundice (yellowing of the skin or eyes), dark urine, unusually pale stools or unexplained fatigue, you need to stop taking Orlistat and seek medical advice from a doctor as soon as possible (2)(3).
Since Orlistat was approved in 1998 in the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) has had reports of some liver issues, including some rare instances of serious liver toxicity. A European review couldn't find evidence to say that Orlistat causes the most serious liver disorders, but it did add warnings about hepatitis and increased levels of liver enzymes (transaminases) to the official information about the medicine (2)(3).
If any of these red-flag symptoms are happening to you, stop Orlistat and see a doctor as soon as you can: jaundice, dark urine, pale stools, ongoing pain in the upper right side of your stomach, unexplained fatigue, loss of appetite with nausea.
People with existing liver disease, those who regularly drink a lot of alcohol, and those taking other medicines that could potentially harm the liver (like some statins or medications for epilepsy) are more at risk. Also, if you’ve been on Orlistat for over a year and haven't had a liver function test, you should ask your doctor to do one.
For what it’s worth, the four-year XENDOS study (with 3,305 participants) showed no significant long-term increases in severe liver side effects with Orlistat compared to a placebo (4).
Can Orlistat cause kidney stones or kidney problems long-term?
Oxalate kidney stones are a rare side effect with Orlistat, experienced by fewer than 1 in every 1000 people according to the MHRA (2). To mitigate the risk of developing these, drink plenty of fluids, eat less food high in oxalates, and tell your doctor if you have chronic kidney disease.
The MHRA Drug Safety Update says Orlistat can rarely (from 1 in 10,000 to 1 in 1000) cause too much oxalate to be in your urine (hyperoxaluria) and damage to the kidneys from oxalate (oxalate nephropathy) (2). The reason for this is that Orlistat stops your body from absorbing fat, and this means calcium stays in your gut. As a result, oxalate is then free to be absorbed by the body and excreted in your urine, and this makes calcium oxalate kidney stones more likely.
To help prevent this, drink a lot of water (at least 2 litres a day), and if you’ve had kidney stones in the past, don't eat too much spinach, rhubarb, beetroot, nuts or tea. Also, if you have long-term kidney problems, have a conversation with your doctor before you begin or continue taking Orlistat. Be particularly alert for pain in your side or back, blood in your urine, pain when you urinate, or really bad pain on one side of your stomach. If you get any of these, see a doctor immediately.
Long-term Orlistat isn't suitable for people who have chronic kidney disease (stage 3b or worse), or for those who have repeatedly had calcium oxalate kidney stones in the past, unless a specialist has told you it’s OK to take it.
Do I need a multivitamin when taking Orlistat, and when should I take it?
Yes, you should take a multivitamin containing vitamins A, D, E and K every day and take it at least two hours before or after Orlistat (taking it at bedtime also works). For those who’ve been using Orlistat for a long time, getting your vitamin D levels checked by a blood test once a year is advisable.
Orlistat decreases how much of the fat-soluble vitamins A, D, E, K and beta-carotene your body absorbs. Over a period of months, this can have an effect on bones, the blood's ability to clot, your eyes and skin, and your cells’ ability to fight damage. A daily multivitamin with A, D, E and K, taken at least two hours before or after Orlistat, may stop you from becoming low on these. If you have Orlistat with your main meals, then bedtime is a good time to take the vitamins.
In the UK, some people are at more risk of problems from lack of essential vitamins such as those on vegan diets, people who have had bariatric surgery in the past, older people, individuals who don't have enough vitamin D in winter, or anyone using Orlistat for 12 months or longer.
If you’ve been on Orlistat for a year, you should ask your doctor for a vitamin D level test, and have it repeated a year later. If you take Warfarin, Orlistat can alter how much vitamin K is absorbed, and so your INR (a measure of blood clotting) will need checking more frequently after you begin Orlistat, and whenever you change your diet. Importantly, you need to inform your GP before changing anything.
When looking at multivitamins in the UK, choose one described as ‘full-spectrum’ or ‘A to Z’ which contains the vitamins A, D, E and K at the UK Reference Nutrient Intake level. Most own-brand products from supermarkets and pharmacies should fit the bill, but remember to read the packaging to make sure. For a practical steer on daily habits that help Orlistat work well long-term, see how to get the best long-term results on Orlistat.
Does long-term Orlistat interact with other common UK medications?
Yes. Orlistat may have clinically relevant long-term interactions with ciclosporin, levothyroxine, antiepileptic medications, Warfarin and the combined contraceptive pill (2)(3). Statins and HRT are generally acceptable to use alongside Orlistat.
Medication | Nature of interaction | What to do |
|---|---|---|
Combined hormonal contraception | Severe diarrhoea may reduce pill absorption | Use contraception back-up (e.g. condoms) for 7 days after any episode (2) |
Levothyroxine | Absorption may be reduced | Stagger dosing by at least 4 hours. Ask for a TSH check if symptoms return (2) |
Warfarin | Altered vitamin K absorption | Monitor INR more frequently after starting Orlistat and after any diet change (3) |
Antiepileptics (carbamazepine, phenytoin, lamotrigine, valproate) | Risk of reduced seizure control | Speak to your neurology or epilepsy doctor before starting Orlistat (2) |
Ciclosporin | Reduced ciclosporin levels | Avoid combining if possible. If unavoidable, stagger by at least 3 hours and monitor levels (2) |
Statins (simvastatin, atorvastatin, rosuvastatin) | No clinically significant interaction | Generally acceptable. No dose change needed (3) |
HRT | No direct interaction | For younger women on HRT for early menopause who also need contraception, the absorption information above applies |
Does long-term Orlistat affect my bowel health?
The initial digestive side effects you may get with Orlistat generally improve after 1 to 3 months as you adapt to the diet. The good news is that it doesn't seem to cause lasting harm to your gut or microbiome (4)(5).
Most people find that the stomach and bowel issues are at their worst during month 1, gradually improving by month 3 as your diet adapts. In fact, a 4-year study called XENDOS found that digestive issues mostly happen in the first year (4).
Long-term, what’s typical is a little flatulence, and now and then you might have some oily spotting after a meal that is high in fat. This is just a sign that you've surpassed the fat limit for that meal, rather than a sign of any damage to your bowel. However, do seek medical advice if you get blood in your stools, persistent diarrhoea for 3 months even though you are eating relatively little fat, unexplained weight loss, or new pain in your stomach. Your GP can help look for other underlying causes.
Hemorrhoids and anal fissures can be caused by urgency to go to the toilet, and this is most likely to happen in the first 3 months. Once your bowel is more regular, they will usually get better on their own or you can use over-the-counter treatments to help or get plenty of fibre in your diet. If the bleeding doesn't stop, you will need to see a doctor as soon as possible. As for your gut microbiome, there’s no consistent evidence that Orlistat permanently changes it and short-term shifts associated with dietary change typically go back to usual.
What should I discuss with a UK prescriber at a long-term review?
In your long-term review for Orlistat, you and your prescriber should discuss how well you’re tolerating the medication, how your weight loss compares to the 5% goal set by NICE, your vitamin levels and liver function tests, and if any other medical conditions have changed since you started Orlistat.
It’s best for a prescriber in the UK to decide if continuing Orlistat for a long time is best for you, or if another approved weight management option would be better. Orlistat has an established safety profile and is well understood for long-term use (4). Other approved weight management treatments, including GLP-1s (such as Wegovy or Mounjaro), are also having their long-term effects studied, including gastrointestinal, pancreatic and gallbladder signals, and are prescription-only medicines subject to their own eligibility criteria and specialist oversight.
For your review, you should have ready (1) your weight at 3, 6, 12 months and most recent measurements, (2) a complete list of all your other medicines, including warfarin, levothyroxine, epilepsy drugs and ciclosporin, (3) current blood test results where possible (Vitamin D, liver function tests, TSH, and INR if you are on warfarin) and, (4) a record of any worrying symptoms like yellowing of the skin (jaundice), pain in your side, diarrhoea which doesn't go away, or unusual bleeding.
You can generally continue Orlistat if you are tolerating it well, losing weight at a good pace, and your blood test results are all acceptable. You should consider changing to something else if you haven't lost 5% of your weight after 3 months (1), if you can't keep to a low-fat diet long term, or if your medical situation changes (for example, being diagnosed with type 2 diabetes, or a personal or family history that affects eligibility such as medullary thyroid carcinoma, MEN2 or pancreatitis for GLP-1 options).
The sensible thing to do is to arrange a consultation with a prescriber in the UK for a thorough clinical assessment. OOP’s Saxenda vs Orlistat guide is one educational resource on injectable weight-loss options, and you can start your free consultation to check whether Orlistat is still the right fit. Don’t combine Orlistat with a GLP-1 injection without specialist oversight.
Frequently asked questions about long-term Orlistat
What are the long-term side effects of taking Orlistat?
The main long-term side effects of Orlistat are fat-soluble vitamin (A, D, E, K) malabsorption, rare oxalate kidney stones (fewer than 1 in 1,000 people), rare hepatitis, and ongoing low-grade bowel changes if the per-meal fat limit is exceeded. The XENDOS 4-year clinical trial data shows no major excess of serious side effects versus placebo. A once-daily multivitamin, adequate hydration and annual GP review may help lower most of these risks.
Is it safe to take Orlistat for more than 6 months or a year?
Yes, Orlistat may generally be tolerable for 12 to 24 months and beyond for most adults, provided the NICE criteria are met (at least 5% weight loss by 3 months), you take a multivitamin with A, D, E and K daily, and you have annual GP review. The XENDOS clinical trial followed patients for 4 years. Rare liver and kidney signs can reflect red-flag symptoms and should prompt an immediate call with a doctor.
Does long-term Orlistat cause liver damage?
Serious liver injury on Orlistat is rare but has been reported, and hepatitis was added as a possible side effect to the official product information. Stop Orlistat and see a doctor if you have signs of jaundice (yellow skin or eyes), dark urine, pale stools, persistent right-upper-quadrant pain or unexplained fatigue. If you’ve been on Orlistat for 12+ months without a liver function test, ask your GP for one.
Can Orlistat cause kidney stones or kidney problems?
Yes, but rarely. The MHRA reports that Orlistat can cause hyperoxaluria and oxalate nephropathy in fewer than 1 in 1,000 people. The way it causes this is fat malabsorption freeing oxalate for excretion by the kidneys. The risk can be lowered by drinking at least 2 litres of water a day, having a lower-oxalate diet if you have a history of kidney stones, and a GP review before starting Orlistat, especially if you have chronic kidney disease.
Do I need to take a multivitamin if I take Orlistat long-term?
Yes. You should take a once-daily multivitamin containing vitamins A, D, E and K at least 2 hours before or after taking Orlistat. Bedtime works well if you take Orlistat with main meals. Orlistat reduces absorption of these fat-soluble vitamins and long-term users risk having low vitamin D, bone health effects and INR fluctuations if on Warfarin. Most UK own-brand multivitamins contain the relevant vitamins.
Will stopping Orlistat make me regain the weight?
Weight regain is possible after stopping any weight-loss treatment, including Orlistat, if the dietary habits aren’t maintained. The XENDOS clinical trial showed some regain in the year after stopping, but roughly half of the lost weight remained off at 4 years with continued lifestyle changes. The medication should be gradually tapered while keeping the same eating habits. Ask your GP about following an NHS weight-management programme for ongoing support.
Does Orlistat affect bowel health in the long run?
For most people, no. Bowel side effects settle within 1 to 3 months as diet adapts, and the 4-year XENDOS clinical trial data show no persistent bowel harm. Occasional oily spotting after a high-fat meal is a sign that you surpassed the recommended fat limit for that meal, not a sign of gut damage. Persistent diarrhoea beyond 3 months, new bleeding, unexplained weight loss or new abdominal pain should be investigated with a doctor for other causes.
Is long-term Orlistat safe with other medications (statins, HRT, contraception)?
Statins and HRT are generally safe to take alongside Orlistat. Combined hormonal contraception may not be fully absorbed during bouts of severe diarrhoea, so back-up contraceptives can be used (e.g. condoms). Warfarin, levothyroxine, antiepileptics and ciclosporin have clinically relevant long-term interactions and need staggered dosing or monitoring as per MHRA guidance. Always tell your GP and pharmacist about every medication you take before starting or continuing Orlistat.
Is Mirena related to Orlistat’s long-term side effects?
No. Mirena is a levonorgestrel intrauterine system used for contraception and heavy menstrual bleeding. It has no pharmacological or mechanistic relationship to Orlistat. If you use Mirena and take Orlistat, there’s no known direct interaction. Severe Orlistat-related diarrhoea can reduce absorption of any other oral medication taken at the same time, but not Mirena itself, which is delivered locally.
Does Orlistat affect long-term contraceptive methods?
Orlistat doesn’t directly interact with hormonal contraception, but severe Orlistat-induced diarrhoea may reduce the absorption of an oral contraceptive pill. Use back-up contraceptives (e.g. condoms) for 7 days after any episode of diarrhoea. Long-acting methods delivered locally (intrauterine systems like Mirena, implants, injections) should not be affected. If you’re planning to be on Orlistat long term, discuss alternative contraceptive options with your GP or pharmacist.
How long is too long to stay on Orlistat?
There’s no strict maximum duration to stay on Orlistat, but NICE guidelines state that treatment should only continue beyond 3 months if you’ve lost at least 5% of starting weight. Most UK prescribers should review you every 6 to 12 months. Long-term users (12+ months) should have an annual GP review, vitamin D check and liver function testing. Switching to a different licensed weight loss treatment may be considered if weight loss has stalled, but this should be a decision discussed with a prescriber.
Is Orlistat a safer long-term option than other prescription weight management treatments?
Orlistat has a longer safety record than current GLP-1 receptor agonists. Other licensed weight management treatments typically achieve greater average weight loss, but their long-term safety profile is still being developed, including gastrointestinal, pancreatic and gallbladder side effects. Which option has the better benefit-risk profile depends on your individual medical circumstances and should be discussed with a qualified prescriber.
References
National Institute for Health and Care Excellence. Overweight and obesity management. NICE guideline NG246. Published 2025 Jan 14.
Medicines and Healthcare products Regulatory Agency. Orlistat safety update. Drug Safety Update. Published 2014 Dec 11.
Xenical 120 mg hard capsules. Summary of Product Characteristics (SmPC). Neon Healthcare Ltd. electronic Medicines Compendium.
Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS): a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-161. PMID 14693982.
Orlistat. NHS inform (Scotland). [Accessed 2026 Apr 17].