If you take metformin and are considering orlistat, there are really two questions to ask. Is there a drug interaction, and is taking both medicines appropriate for you? For adults in the UK who take metformin for type 2 diabetes or another condition and are considering orlistat for weight management, these are different questions.
The short answer is that available evidence has not found a clinically significant pharmacokinetic interaction between orlistat and metformin. This means orlistat does not appear to significantly change how metformin is absorbed or processed. However, both medicines can cause digestive side effects, so taking them together may increase problems such as diarrhoea, urgency, bloating or stomach discomfort. This is something to discuss with the healthcare professional managing your treatment.
Below, we look at what the evidence says about using orlistat with metformin, including weight loss and blood glucose control, possible side effects, what to monitor and when to speak to a healthcare professional.
Do Orlistat and Metformin Interact?
Based on the available evidence, there does not appear to be a clinically significant pharmacokinetic interaction between the two medicines.
What the Pharmacokinetic Data Shows
A comparative pharmacokinetic study in healthy volunteers looked at metformin taken alone and metformin taken with orlistat. The results showed that the two formulations were bioequivalent, with no pharmacokinetic interaction identified. In simple terms, orlistat did not appear to significantly change the amount of metformin reaching the bloodstream or how quickly it was absorbed.
The reason also makes sense from how the medicines work. Orlistat acts mainly inside the gut by blocking enzymes that break down dietary fat, which reduces the amount of fat absorbed from food. Metformin works in a different way and does not depend on dietary fat absorption for its effect.
There is also clinical evidence from people with type 2 diabetes. A 52 week randomised study looked at orlistat in people already taking metformin, either alone or with a sulphonylurea, and found improvements in weight and several measures of blood glucose control compared with placebo.
What Orlistat Does Interact With
The fact that orlistat does not appear to interact significantly with metformin does not mean it has no medicine interactions. It can affect the absorption or effectiveness of some other medicines, so it is important to check your full medicine list before starting it.
| Medicine or group | Why it matters |
|---|---|
| Levothyroxine | Orlistat may reduce its absorption, so the medicines may need to be taken at different times and thyroid function may need monitoring |
| Anticoagulants such as warfarin | Orlistat can reduce vitamin K absorption, which may affect clotting control and INR monitoring |
| Ciclosporin | Orlistat can reduce ciclosporin levels, so the combination is generally avoided or requires specialist monitoring |
| Amiodarone | Orlistat may reduce absorption, so medical advice is recommended |
| Antiepileptic medicines | Absorption may be affected, which could affect seizure control |
| HIV medicines | Orlistat may reduce absorption and could affect treatment effectiveness |
| Some medicines for depression or anxiety | The NHS lists some of these medicines as medicines that may not mix well with orlistat |
| Fat soluble vitamin supplements | Orlistat can reduce absorption of vitamins A, D, E and K, so timing of supplements matters |
The exact interaction depends on the medicine you take, so do not rely on a general interaction list alone. Tell your doctor or pharmacist about all your prescription medicines, over the counter medicines, vitamins and supplements.
Two questions people often ask are also worth covering. Fluconazole is not listed among the recognised orlistat interactions in the current UK product information. However, that does not mean there can never be a medicine interaction in a person taking several medicines. Your full medication list should still be checked.
The contraceptive pill is different. Orlistat does not appear to directly reduce the effectiveness of oral contraception, but severe diarrhoea can reduce how well an oral contraceptive is absorbed.
The Real Issue: Two Medicines That Both Affect the Gut
For many people, the bigger day to day issue is not a direct drug interaction. It is the fact that both medicines can cause digestive side effects.
Why the Side Effects Overlap
Metformin commonly causes nausea, diarrhoea, stomach pain and loss of appetite, particularly when treatment is first started. These side effects may improve as the body gets used to the medicine.
Orlistat causes a different group of digestive side effects. These can include oily or fatty stools, oily spotting, wind with discharge and a greater need to use the toilet. These effects are linked to the way orlistat prevents some dietary fat from being absorbed. Eating a meal that is high in fat can make these effects more likely.
Taking both medicines does not automatically mean you will have worse side effects, but there can be more digestive symptoms to deal with. If you start both at the same time and develop diarrhoea or stomach discomfort, it can also be harder to work out which medicine is causing the problem.
The Problem That Creates
If you start both medicines at the same time and your stomach reacts badly, it may be difficult to tell which medicine is responsible. That matters because the next step may be different depending on the cause.
Metformin related digestive symptoms may improve with time or may need a discussion about the dose or formulation. Orlistat related symptoms are often linked to the amount of fat in a meal.
For this reason, your prescriber may decide that introducing medicines one at a time is easier to manage. Do not change or stop your medicines without discussing it with the healthcare professional looking after you.
| What you notice | More typical of | What may help |
|---|---|---|
| Oily or fatty stools, oily spotting, wind with discharge | Orlistat | Keeping meals within the dietary advice given with orlistat |
| Urgent or frequent bowel movements after a fatty meal | Orlistat | Reducing the amount of fat in meals |
| Nausea and stomach discomfort soon after starting or increasing a dose | Metformin | These symptoms may settle; speak to your prescriber if they continue |
| Metallic taste or reduced appetite | Metformin | These can occur with metformin and should be discussed if they persist |
| Diarrhoea | Both | Look at when it happens and whether it follows meals or a change in medicine |
What the Evidence Says About the Combination
The combination has been studied, including in people with type 2 diabetes who were already taking metformin.
The 52 Week Weight Loss Trial in People Taking Metformin
A randomised, double blind study looked at people with obesity and type 2 diabetes who were already taking metformin, either alone or alongside a sulphonylurea. Participants received either orlistat or placebo alongside a mildly reduced calorie diet and a weight management programme for 52 weeks.
After 52 weeks, the orlistat group had lost 5.0% of body weight compared with 1.8% in the placebo group. Waist circumference also fell by 4.8 cm compared with 2.8 cm. HbA1c fell by 1.1% compared with 0.2%, while fasting plasma glucose fell by 1.9 mmol/l compared with 0.3 mmol/l. The study also found improvements in total cholesterol, apolipoprotein B, beta cell function and insulin resistance.
The study also found that people taking orlistat needed less diabetes medication than those taking placebo. This is one reason blood glucose and diabetes treatment may need to be reviewed as weight changes.
These are results from a clinical trial, not a guarantee of what will happen for an individual. Weight loss and changes in blood glucose vary from person to person.
Diabetes Prevention and Insulin Sensitivity
For people who do not have diabetes, the XENDOS trial provides useful evidence. It included 3,305 adults with a BMI of 30 or above who were assigned to lifestyle changes plus either orlistat or placebo for four years.
The cumulative incidence of type 2 diabetes was 6.2% with orlistat compared with 9.0% with placebo. This represented a 37.3% relative risk reduction.
The difference was particularly noticeable in people who already had impaired glucose tolerance at the start of the study. In this group, diabetes developed in 18.8% of people taking orlistat compared with 28.8% taking placebo. There was no significant difference in people who had normal glucose tolerance at the start of the study.
The results are generally understood in the context of the weight loss achieved with orlistat and lifestyle changes. They should not be taken to mean that orlistat will prevent diabetes in every person who takes it.
The Monitoring Point That Gets Missed
If weight loss improves your blood glucose control, the amount of diabetes medicine you need may change. This is why diabetes treatment should be reviewed while you are taking orlistat rather than simply continuing the same medicines without monitoring. The UK product information specifically advises monitoring diabetes treatment because weight loss can improve metabolic control.
Metformin on its own does not usually cause low blood sugar. The risk can be different if you also take a sulphonylurea or insulin.
Tell the healthcare professional managing your diabetes that you are considering orlistat before starting it.
- Ask whether you need to check your blood glucose more often while losing weight
- Know the symptoms of low blood sugar if you take insulin or a sulphonylurea
- Do not change your diabetes medicine yourself because you have lost weight
- Have your progress and treatment reviewed as advised by your prescriber. Orlistat is normally reviewed after 12 weeks, and UK guidance recommends stopping it if you have not lost at least 5% of your starting body weight by then.
Metformin Is Not a Weight Loss Medicine in the UK
This is worth making clear because people often search for metformin and orlistat as though they are two weight loss medicines that are designed to work together.
Metformin is licensed for the treatment of type 2 diabetes. It is also used off label for conditions such as polycystic ovary syndrome. Some people lose weight while taking metformin, but it is not licensed as a weight loss medicine in the UK.
So, when these medicines are used together, the aim is not simply to combine two weight loss medicines. Metformin is treating an underlying condition, while orlistat may be considered for weight management where it is clinically appropriate.
If weight management is what you are looking into, there are several treatment options. They differ in how they work, who they are suitable for and how they are taken.
You can compare the available approaches through our medically supervised weight loss options.
There is more detail on how injectable treatment works and who it suits on the Mounjaro treatment page. Which treatment is appropriate depends on an individual clinical assessment, and Mounjaro and orlistat work in very different ways.
Practical Points Worth Getting Right
Fat Soluble Vitamins
Orlistat can reduce the absorption of fat soluble vitamins A, D, E and K, as well as beta carotene. For this reason, UK product information recommends taking a multivitamin containing these vitamins, usually at bedtime and at least 2 hours after the last orlistat dose.
Do not assume that taking a multivitamin at the same time as orlistat is better. Ask your pharmacist or prescriber about the best timing for your particular products.
Vitamin B12 and Metformin
Long term metformin use can reduce vitamin B12 levels in some people. This is separate from the way orlistat works, but it is still worth remembering if you take both medicines.
If you feel unusually tired, develop numbness or tingling, or have other symptoms that concern you, mention them to your doctor. They can decide whether your vitamin B12 level needs checking.
The Contraceptive Pill
Orlistat does not appear to directly reduce the effectiveness of the combined oral contraceptive pill. The concern is severe diarrhoea, which can affect absorption of oral contraception. NHS guidance advises using additional barrier contraception, such as condoms, if you have severe diarrhoea or diarrhoea lasting more than 24 hours while taking orlistat.
Metformin can also cause diarrhoea, so this is particularly useful to know if you take both medicines.
Levothyroxine
Orlistat may reduce the absorption of levothyroxine and can affect thyroid control. If you take levothyroxine, speak to your doctor or pharmacist before starting orlistat. You may need to take the medicines at different times and have your thyroid function monitored.
Why This Is a Conversation With Your GP, Not Just a Form
Online assessment can be useful, and a prescriber reviewing your medical history and medicines is still carrying out a clinical assessment. But if you take metformin, you are already being treated for a long term condition that may require regular blood tests and medication reviews.
Adding orlistat can affect your digestive symptoms, weight and blood glucose control. In some people, this may mean their diabetes treatment needs to be reviewed.
The most useful step is to tell your GP, diabetes team, pharmacist or other prescriber what you are considering. Make sure the person prescribing orlistat knows that you take metformin and has a complete list of your medicines.
A proper assessment should consider your medical history, current medicines and any conditions that could make orlistat unsuitable. Treatment should be based on your individual circumstances rather than simply whether two medicines appear on an interaction checker.
When to Check Before Starting
- You have chronic kidney disease, a condition that affects nutrient absorption, or cholestasis
- You take a sulphonylurea or insulin alongside metformin
- You take levothyroxine, an anticoagulant, ciclosporin, amiodarone, an antiepileptic or HIV medicine
- You are pregnant, breastfeeding or trying to conceive
- You have a history of significant kidney or gallbladder problems
- You have had a previous reaction to orlistat
Orlistat is not used during pregnancy and is contraindicated during breastfeeding under current UK product information. It is also contraindicated in chronic malabsorption syndrome and cholestasis. People with chronic kidney disease should speak to a doctor before starting it because of a possible risk of kidney complications.
Seek prompt medical advice if you develop severe or persistent abdominal pain, rectal bleeding, yellowing of the skin or eyes, or symptoms of a serious allergic reaction.
