Mounjaro and orlistat are both licensed weight loss and weight management medications for people with a body mass index (BMI) of above 30 – or 27 with additional risk factors, such as high blood pressure. But can you take them together safely?

While there are no confirmed drug interactions between these two medications, we don’t recommend using orlistat alongside GLP-1 weight loss injections like Mounjaro.

In this blog, we’ll explain why. We’ll explore how each medication works and the potential risks of taking both together – including worsening Mounjaro side effects and an increased risk of nutrient deficiencies.

Mounjaro and Orlistat: How They Work

Mounjaro (Tirzepatide): Mounjaro is a weekly weight loss injection that works by mimicking two key hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).

By mimicking these hormones, Mounjaro helps to:

  • Suppress Your Appetite: Mounjaro slows digestion, helping you feel full quicker and stay feeling fuller for longer, which naturally reduces food intake.
  • Improve Blood Sugar Control: Mounjaro helps the pancreas release insulin in response to meals. By slowing your digestion, it helps regulate post-meal blood sugar spikes by allowing your body to absorb glucose more gradually.

Studies show Mounjaro is highly effective for weight loss. At the highest dose (15 mg), participants in one study lost an average of 20.9% of their total body weight over 72 weeks.

Orlistat: Orlistat is a weight loss medication, which is taken three times a day. It has been licensed in the UK since 1998.

Unlike Mounjaro, orlistat does not affect appetite or blood sugar regulation. Orlistat works by blocking the action of enzymes, called lipase, that break down dietary fat in foods. In blocking these enzymes, orlistat prevents fat from being digested.

As a result, absorption of fat is reduced by around 30%. This leads to fewer calories absorbed by the body, which is an essential part of weight loss.

Mounjaro and Orlistat: Can I Take Them at the Same Time?

We advise that you do not use Mounjaro and Orlistat together, as their effects on weight loss and digestion can overlap. This could lead to excessive weight loss and increased side effects.

Mounjaro already suppresses your appetite. So when you take it alongside orlistat – which prevents your body from absorbing fat – it increases your risk of nutritional deficiencies. Getting enough nutrients is crucial for maintaining essential bodily functions, like metabolism, circulation and digestion.

It is vital to approach weight management under medical supervision, without combining different weight loss medications. This will ensure your nutritional needs are met. Consult the prescriber of both medications before taking them together.

While there are no known direct interactions between Mounjaro and orlistat, their combined use has not been extensively studied.

Potential Risks

Hypoglycaemia (Low Blood Sugar): If you are using other medications to treat type 2 diabetes, weight loss can increase your sensitivity to insulin, which may lead to hypoglycaemia. If you experience significant weight loss, you may need to adjust your Mounjaro dose, particularly if you are taking it for diabetes.

Vitamin Deficiencies: Orlistat reduces fat absorption, which could impact the body’s ability to absorb fat-soluble vitamins (A, D, E, and K) and some medications. As Mounjaro reduces appetite and calorie intake, taking them together could increase your risk of vitamin deficiencies over time.

Side Effects From Both Drugs: Both Mounjaro and orlistat are associated with gastrointestinal side effects (in the stomach). Mounjaro can cause nausea, constipation and diarrhoea, while orlistat may lead to oily stools, bloating and diarrhoea. Some people experience digestive discomfort when combining Mounjaro and orlistat, especially with high-fat meals.

Potential Impact on Other Medications: Because orlistat reduces fat absorption, it may also affect how certain fat-soluble medications work. This includes:

  • Oral contraceptives – effectiveness may be reduced in some cases.
  • Blood thinners (e.g. warfarin) – vitamin K levels may be altered.
  • Certain thyroid and immunosuppressant medications – absorption could be affected.

This list is not comprehensive, and other interactions may also occur. Consult a healthcare professional for more information.

Taking Mounjaro and Orlistat Safely 

We do not recommend our patients take Mounjaro alongside orlistat. You should avoid using them together unless specifically advised by a healthcare professional who is prescribing you both of these medications.

If you do take orlistat and Mounjaro together, you will have to monitor your vitamin levels and consider supplements. Take supplements at least two hours before or after orlistat to ensure they are adequately absorbed, especially vitamins A, D, E, and K.

Seek guidance from a healthcare professional if you experience any unpleasant side effects or experience rapid weight loss. If you have diabetes, regularly monitor your blood sugar levels and consult your doctor to determine if you need to change your dose.

Take a Long-Term, Balanced Approach to Weight Loss

If you are thinking of taking orlistat to speed up the rate at which you lose weight on Mounjaro, it’s important to remember Mounjaro is a long-term treatment. Aim for steady and sustainable weight loss of 1-2 lbs per week rather than focusing on fast results.

Mounjaro is most effective when combined with a healthy diet and regular exercise. Try to make small, manageable lifestyle changes – like adding a 20-minute walk to your day or swapping sugary snacks for whole-food alternatives.

If you’re thinking about combining Mounjaro and orlistat, a healthcare provider can give you personalised advice. Don’t hesitate to ask for help, as it’s the best way to ensure safe and effective weight loss. If you’re a patient with Simple, call us on 0141 774 5023.

Key Takeaways

  • No Confirmed Interactions but We Don’t Recommend Using Both Together: There are no known direct interactions between Mounjaro and orlistat. But it’s likely the combined effect of the medications will make the negative aspect of each treatment worse. It will increase your risk of malnutrition and side effects.
  • Orlistat and Mounjaro Have Different Mechanisms, but Effects Can Overlap: Mounjaro regulates blood sugar and appetite, while orlistat blocks fat absorption. However, their similar effects on digestion and weight loss may require close monitoring.
  • Increased Risk of Side Effects: Both medications can cause gastrointestinal issues, such as nausea, bloating, and diarrhoea. While these are common side effects, they may worsen when taken together.
  • Nutrient Absorption Concerns: Orlistat reduces fat absorption, which can impact the intake of fat-soluble vitamins (A, D, E, K), potentially exacerbated by Mounjaro’s appetite suppression.
  • Medical Guidance is Essential: Consulting a healthcare provider is crucial before combining these medications, especially for those managing diabetes or taking other medications.

Clinically reviewed by: Richard Wood, GPhC reg: 2078802

References: 

DrugBank. (n.d.). Tirzepatide: Uses, interactions, mechanism of action. DrugBank Online. https://go.drugbank.com/drugs/DB15171

Jastreboff, A.M., Aronne, L.J., Ahmad, N.N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M.C. and Stefanski, A. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, [online] 387(3). doi:https://doi.org/10.1056/nejmoa2206038.

DrugBank. (n.d.). Orlistat: Uses, interactions, mechanism of action. DrugBank Online. https://go.drugbank.com/drugs/DB01083

Medicines and Healthcare products Regulatory Agency. (2014, December 11). Orlistat safety update. GOV.UK.https://www.gov.uk/drug-safety-update/orlistat-safety-update

Drugs.com. (n.d.). Mounjaro and Orlistat interactions checker. Retrieved from https://www.drugs.com/drug-interactions/mounjaro-with-orlistat-4363-20051-1756-0.html

‘Orlistat: effect on fat-soluble vitamins in adolescents’ (2002) Inpharma Weekly, &NA;(1351), p. 17. Available at: https://doi.org/10.2165/00128413-200213510-00041 

Orlistat (oral route). (2025, February 1). Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/orlistat-oral-route/description/drg-20065184