Understanding the Gastrointestinal Side Effects of Metformin

Do you have type 2 diabetes and have been prescribed metformin to help lower your blood glucose? 

Have you experienced unpleasant side effects such as nausea, diarrhea, gas, and bloating? 

You’re not alone – it is estimated that taking metformin, a biguanide medication, can cause gastrointestinal upset in 20-30% of people. Some people may be so intolerant that they must stop taking it altogether.

Several years ago, I worked in weight management and general nutrition counseling. I educated and counseled people on nutrition strategies to help reduce weight and promote overall health. I can argue that a majority of my patients also had multiple comorbidities, such as type 2 diabetes, and were on numerous pharmaceutical medications to manage their disease.

My first goal was to teach them how to manage their conditions and heal their body through nutrition, as I believe that food is medicine. Some of my patients were successful with coming off medications (such as metformin) once they had reasonable diet control and made lifestyle changes. However, for some, taking drugs may be a long-term solution as they cannot manage their disease with diet and lifestyle changes alone.

Let’s briefly explain how metformin acts and what it is often prescribed for:

Metformin is a prescription medication to lower blood glucose levels and is a first-line treatment for diabetics. It also has some off-label uses, including treating polycystic ovarian syndrome (PCOS), obesity, infertility, and, more recently, anti-aging. 

It acts through several proposed mechanisms to promote blood glucose regulation:

o   Reduced liver glucose production

o   Increased insulin sensitivity in muscles (allowing for glucose to be easily used vs. accumulating in blood circulation)

o   Delay in absorption or increased usage of glucose in the intestines

o   Alteration of the gut microbiome (possible dysbiosis)

o   Increasing secretion of glucagon-like-peptide-1 (GLP-1), which plays a role in controlling appetite and promoting insulin activity

Metformin has been proposed to alter the gut microbiome. Could these proposed alterations lead to dysbiosis of the gut microbes, causing some unpleasant gastrointestinal side effects?

 A 2022 study out of Biomedicine & Pharmacotherapy identified differences in 6 bacterial species between people tolerant to metformin vs. intolerant to metformin, suggesting dysbiosis in individuals who are intolerant to metformin. How this occurs and why still needs to be understood. Other studies have identified similar trends. However, it is worth noting that some researchers have yet to find consistent trends, especially when comparing animal to human subject research.

What can someone on metformin do to help reduce gastrointestinal symptoms?

Consider taking a probiotic supplement. Speak with your medical provider or dietitian to determine what strain might be the best for you. A 2023 randomized controlled trial revealed that taking a probiotic had synergistic effects alongside metformin use. Blood sugars were better maintained, and side effects were minimal, if any. This was due to increased SCFA-producing bacteria and the promotion of GLP-1 secretion in the intestines to help lower blood sugars. One of the strains used, Lactobacillus rhamnosus Probio-M8, has been shown to mitigate type 2 diabetes symptoms in hyperglycemic mice possibly.

Since metformin does increase the production of the hormone glucagon-like-peptide-1 (GLP-1), this can slow down the movement of food through the digestive system, consequently resulting in symptoms such as nausea and vomiting. Paired with metformin’s capability to interfere with the absorption of carbohydrates in the small intestine, this can further lead to an accumulation of undigested carbohydrates in the large intestine (think- gas, bloating). 

Often these side effects can be managed with diet changes or even medication dose adjustments, so if you are experiencing these symptoms, speak with your medical provider and registered dietitian for ways to reduce the severity of your symptoms.

What can you do right now to improve your overall health?

• Avoid high intake of processed foods containing added sugars and unhealthy fats.
• Consume a high-quality diet with lean proteins, fruits, and vegetables. Focus on prebiotic foods.
• Avoid sugar-sweetened beverages and choose water. 
• Get regular exercise and focus on finding enjoyable ways to move to help reduce overall body fat and increase or improve muscle tone. 
• If you suffer from IBD/IBS, talk with a dietitian to find ways to eat a healthy diet without triggering your symptoms.

1. _{Chen, Y., Shen, X., Ma, T., Yu, X., Kwok, L. Y., Li, Y., Sun, Z., Li, D., & Zhang, H. (2023). Adjunctive Probio-X Treatment Enhances the Therapeutic Effect of a Conventional Drug in Managing Type 2 Diabetes Mellitus by Promoting Short-Chain Fatty Acid-Producing Bacteria and Bile Acid Pathways. mSystems, 8(1), e0130022.} 
2. _{Díaz-Perdigones, C. M., Muñoz-Garach, A., Álvarez-Bermúdez, M. D., Moreno-Indias, I., & Tinahones, F. J. (2022). Gut microbiota of patients with type 2 diabetes and gastrointestinal intolerance to metformin differs in composition and functionality from tolerant patients. Biomedicine & Pharmacotherapy, 145, 112448.}
3. _{Zhang, Q., & Hu, N. (2020). Effects of Metformin on the Gut Microbiota in Obesity and Type 2 Diabetes Mellitus. Diabetes, metabolic syndrome and obesity : targets and therapy, 13, 5003–5014.}
4. _{Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577–1585.}