Get a free visit for ED treatment. Start now

Last updated: Dec 02, 2020
9 min read

Metformin: potential interactions and side effects

Disclaimer

If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

We don’t always think of alcohol as a drug, but it’s a powerful one! It interferes with many medications, and it can be dangerous for people with certain conditions to drink. 

Before starting on metformin (or any medication), it’s important to know about any drug interactions and whether you can drink alcohol while taking it. Your healthcare provider will be able to answer your questions if you’re unsure about anything. 

Men’s healthcare, without the waiting room

Connect with a US-licensed healthcare provider about ED, premature ejaculation, hair loss, and more.

Learn more

Can you drink alcohol while taking metformin?

There are no specific contraindications for drinking alcohol—in moderate amounts—while taking metformin. According to the U.S. Department of Health and Human Services, moderate drinking generally means one drink per day for women and two drinks per day for men (USDA, 2015). Binge drinking or heavy alcohol use is not recommended while on metformin, though. Here’s why: 

Metformin can cause lactic acidosis

The reason heavy drinking isn’t a good idea while taking metformin is because of the increased risk for lactic acidosis. Metformin is a very safe medication with almost no adverse effects, but in extremely rare cases, it’s been associated with a condition called lactic acidosis, when there’s a dangerous increase in lactic acid in the blood (Stang, 1999). This can lead to kidney or liver failure. 

The association between metformin and lactic acidosis is so rare that some researchers believe it’s not worth worrying about at all (Misbin, 2004). 

Even though the risk is very low, it’s not recommended for people at higher risk of developing lactic acidosis to take metformin. This includes people with severely lowered kidney function or advanced liver disease, as well as people who drink alcohol heavily. 

Alcohol can increase the risk of lactic acidosis

Since there’s a concern about the increased risk of lactic acidosis when taking metformin, it’s not a good idea to mix metformin with heavy alcohol consumption. This is because alcohol itself increases the risk of lactic acidosis (Fulop, 1989). Even small amounts of alcohol cause a buildup of lactic acid in the blood, but not enough for moderate drinking to be a concern. The more you drink, the more lactic acid increases in your blood, and the greater your risk for developing lactic acidosis.

There’s also an increased risk for lactic acidosis in people with severe liver problems, which can happen with prolonged excessive alcohol use.

It’s important that you are open and honest with your healthcare providers about your drinking habits and that you follow their medical advice carefully. 

Other metformin interactions

Alcohol is not the only drug that might interact with metformin (Maideen, 2017). Here are some other possible drug interactions: 

  • Iodinated contrast (used in imaging tests)
  • Certain anticancer drugs (specifically vandetanib and drugs that fall under the class called tyrosine kinase inhibitors)
  • Some antimicrobial drugs (such as cephalexin and rifampin)

There’s also a possible interaction with certain HIV medications, such as dolutegravir (Song, 2016).

Most of these interactions are flagged for the same reason as excessive alcohol drinking—because taking these medications can raise the body’s lactic acid levels. Since there’s a rare possibility of developing lactic acidosis while on metformin, there’s concern about taking anything else that may raise lactic acid levels further. 

If you’re taking any of these medications, that doesn’t necessarily mean that metformin is off the table for you. Your healthcare provider may just want to monitor you closely.

What should you not eat when taking metformin?

While you shouldn’t drink too much alcohol while taking metformin, you can eat anything you like with this medication. Some medications have restrictions on eating grapefruit or foods that are high in fat, but there aren’t any restrictions like this with metformin. 

It is recommended to take metformin with food to cut down on any gastrointestinal (GI) symptoms, which are quite common with metformin (Bonnet, 2016). 

Safety concerns with metformin

Metformin might have a lot of GI side effects, but it’s quite safe, and even people who have side effects can usually tolerate this medication (Diabetes Prevention Program Research Group, 2012). Not only is it safe, but there’s even research showing that metformin can decrease death rates from diabetes-related causes, as well as all other causes in patients with type 2 diabetes (Markowicz-Piasecka, 2017). 

Lactic acidosis is the only possible serious adverse complication associated with metformin, but it is exceedingly rare (so rare that some researchers think it’s not a cause for concern at all) (Misbin, 2004). 

Still, it’s important to be careful to avoid anything that may increase the risk of lactic acidosis while taking metformin, such as heavy alcohol drinking. Similarly, metformin is also not recommended for patients with advanced liver or kidney disease since those people are at higher risk of developing lactic acidosis. There’s no contraindication for patients with mild to moderate kidney disease, but those patients might need to be monitored more closely (MacCallum, 2019). 

At one point, metformin was considered unsafe for patients with a history of heart attack or congestive heart failure (CHF), but it’s been shown to be safe—and possibly even beneficial—in these patients (Tahrani, 2007). 

Can you just stop taking metformin?

Like any medication, it’s important to follow your healthcare provider’s medical advice if you want to stop taking metformin. There’s no danger in stopping, but your healthcare provider will want to know why you’re thinking about stopping metformin so he or she can make sure you’re on the right medications and dosages to help your condition. 

If you stop taking metformin, any positive effects of the medication will stop, too. 

Metformin warnings

There is one boxed warning from the FDA for metformin (Crowley, 2016). The drug information label warns against anyone with advanced kidney disease from taking metformin due to the increased risk of lactic acidosis. 

What is metformin used to treat?

Metformin is only FDA-approved to treat type 2 diabetes, but it’s also often used in patients with moderate insulin resistance (prediabetes) to prevent their condition from progressing into diabetes (Lilly, 2009). 

Some researchers think metformin has the potential to be the “perfect” drug for treating a wide range of medical conditions (Markowicz-Piasecka, 2017). We don’t have quite enough research yet, but there’s some promising evidence that metformin might be useful in other conditions, such as cancer, heart disease, and aging. For now, though, metformin isn’t used to treat those conditions. 

There is, however, one off-label use for metformin that many healthcare providers do rely on with their patients. While not FDA-approved for this purpose, metformin is quite effective at treating polycystic ovary syndrome (PCOS), a condition that causes many hormonal symptoms in women (Johnson, 2014). These can range from mild symptoms like acne and excess hair growth to severe symptoms like infertility and early pregnancy loss. 

How does metformin treat type 2 diabetes?

Metformin works by decreasing glucose production in the liver, which lowers the body’s blood sugar levels and improves glycemic control and insulin sensitivity (Lv, 2020). This is an important function for people with type 2 diabetes since their cells do not process insulin properly, which causes their blood glucose levels to be much higher than they should be. 

Metformin works well along with key lifestyle changes to bring blood sugar back down to a healthy level. Be aware that GI symptoms are pretty common, though, when taking metformin, since it’s primarily absorbed in the small intestine and causes a few important reactions in the gut, including increasing bile acid and changing the gut microbiome (McCreight, 2016). 

What is Glucophage?

Glucophage is one of the most commonly prescribed brand names for metformin (National Library of Medicine, 2018). It comes in an immediate-release formula, taken twice a day, and as an extended-release tablet (called Glucophage XR), taken once a day. The extended-release version is often the better choice if you experience GI symptoms on the immediate-release formula (Jabbour, 2011). 

Your healthcare provider might also prescribe one of the other brand names of metformin: Glumetza, Riomet, or Fortamet. Regardless of the name on the bottle, be careful not to overdo it with alcohol drinking while taking this medication. 

Common side effects of metformin

One of the possible downsides of metformin is its side effect profile. The biggest complaints are GI symptoms, such as nausea, diarrhea, vomiting, metallic taste in the mouth, and abdominal pain (Bonnet, 2016). These symptoms can happen in up to 25% of people, but they’re generally mild and tolerable. Only about 5% of people need to stop metformin because of severe GI symptoms (McCreight, 2016). 

Taking metformin on an empty stomach can make GI symptoms more likely, so you may want to take it with food. Your healthcare provider may also start you on a lower dose and slowly increase your dosage or switch you to extended-release metformin to try to avoid GI symptoms. 

Another known side effect is vitamin B12 deficiency, which can happen in up to 20% of patients (de Jager, 2010). Your healthcare provider may recommend a vitamin B12 supplement if your levels drop too much. 

The most serious side effect associated with metformin is lactic acidosis, but this is very rare (Foucher, 2020). Lactic acidosis is when the lactic acid levels in the blood get dangerously high. This is why it’s not recommended to drink alcohol heavily while taking metformin since the combination of metformin and excessive alcohol can raise lactic acid levels in the blood. 

Metformin diarrhea

The most common GI side effect of metformin is diarrhea, affecting over 60% of patients who complain of GI symptoms (Fatima, 2018). 

We don’t know for sure why diarrhea is so common on metformin, but it’s likely because taking metformin causes more fluid to be drawn into the gut while increasing muscle contractions in the GI tract. The way this works is that metformin lowers the amount of bile salts that get absorbed into the gut while raising the gut’s serotonin signaling. 

Even without metformin, though, patients with type 2 diabetes experience diarrhea at higher rates than the rest of the population—about 20% of all patients with type 2 diabetes (Gould, 2009). So, it’s possible that adding metformin into the mix just exacerbates this problem. As many as 50% of patients with diabetes taking metformin experience diarrhea as a side effect. 

Can metformin cause weight loss?

One reason many patients and healthcare providers love metformin is that it can contribute to modest weight loss (Apolzan, 2019). At the very least, it doesn’t cause weight gain. 

Many patients with type 2 diabetes are concerned about gaining weight on their medications since weight gain is so common with other drugs used for type 2 diabetes (Provilus, 2011). These include a class of drugs called sulfonylureas (some examples are glimepiride, glipizide, and glyburide), another class called thiazolidinediones or TZDs (Avandia and Actos are the two drugs in this class), and insulin. 

Be open with your healthcare provider

Before starting on metformin, let your healthcare provider know about your full medical history, including any medications you’re taking. If you do drink more than a moderate amount of alcohol, share that information so you can work with your healthcare provider to figure out a good treatment plan.

References

  1. Apolzan, J. W., Venditti, E. M., Edelstein, S. L., Knowler, W. C., Dabelea, D., Boyko, E. J., et al. (2019). Long-term weight loss with metformin or lifestyle intervention in the diabetes prevention program Outcomes Study [Abstract]. Annals of Internal Medicine, 170(10), 682-690. doi:10.7326/M18-1605. Retrieved from https://pubmed.ncbi.nlm.nih.gov/31009939/
  2. Bonnet, F. & Scheen, A. (2016). Understanding and overcoming metformin gastrointestinal intolerance. Diabetes, Obesity and Metabolism, 19(4). doi:10.1111/dom.12854. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27987248/ 
  3. Crowley, M. J., Diamantidis, C. J., & McDuffie, J. R. (2016). Metformin use in patients with historical contraindications or precautions. Washington (DC): Department of Veterans Affairs (US). APPENDIX A, FDA SAFETY ANNOUNCEMENTS FOR METFORMIN. Available from https://www.ncbi.nlm.nih.gov/books/NBK409379/ 
  4. De Jager, J., Kooy, A., Lehert, P., Wulffelé, M. G., Van der Kolk, J., Verburg, J., et al. (2010). Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: Randomised placebo controlled trial [Abstract]. BMJ, 340(C2181). doi:10.1136/bmj.c2181. Retrieved from https://pubmed.ncbi.nlm.nih.gov/20488910/ 
  5. The Diabetes Prevention Program Research Group. (2012). Long-term safety, tolerability, and weight loss associated with metformin in the diabetes prevention program outcomes study. Diabetes Care, 35(4), 731-737. doi:10.2337/dc11-1299. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308305/ 
  6. Fatima, M., Sadeeqa, S., & Nazir, S. U. (2018). Metformin and its gastrointestinal problems: A review. Biomedical Research, 29(11). doi:10.4066/biomedicalresearch.40-18-526. Retrieved from https://www.alliedacademies.org/articles/metformin-and-its-gastrointestinal-problems-a-review-10324.html
  7. Foucher, C. D. & Tubben, R. E. (2020). Lactic acidosis. StatPearls. Retrieved Nov. 9, 2020 from https://www.ncbi.nlm.nih.gov/books/NBK470202/ 
  8. Fulop, M. (1989). Alcoholism, ketoacidosis, and lactic acidosis [Abstract]. Diabetes/Metabolism Reviews, 5(4), 365-378. doi:10.1002/dmr.5610050404. Retrieved from https://pubmed.ncbi.nlm.nih.gov/2656160/
  9. Gould, M. & Sellin, J. H. (2009). Diabetic diarrhea. Current Gastroenterology Reports, 11(5), 354-359. doi:10.1007/s11894-009-0054-y. Retrieved from https://pubmed.ncbi.nlm.nih.gov/19765362/
  10. Jabbour, S. & Ziring, B. (2011). Advantages of extended-release metformin in patients with type 2 diabetes mellitus [Abstract]. Postgraduate Medicine, 123(1), 15-23. doi:10.3810/pgm.2011.01.2241. Retrieved from https://pubmed.ncbi.nlm.nih.gov/21293080/ 
  11. Johnson, N. P. (2014). Metformin use in women with polycystic ovary syndrome. Annals of Translational Medicine, 2(6), 56th ser. doi:10.3978/j.issn.2305-5839.2014.04.15. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200666/ 
  12. Lilly, M., & Godwin, M. (2009). Treating prediabetes with metformin: Systematic review and meta-analysis. Canadian Family Physician, 55(4), 363-369. Retrieved Nov. 11, 2020 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669003/ 
  13. Lv, Z. & Guo, Y. (2020). Metformin and its benefits for various diseases. Frontiers in Endocrinology, 11(191). doi:0.3389/fendo.2020.00191. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212476/ 
  14. MacCallum, L. & Senior, P. A. (2019). Safe use of metformin in adults with type 2 diabetes and chronic kidney disease: Lower dosages and sick-day education are essential [Abstract]. Canadian Journal of Diabetes, 43(1), 76-80. doi:10.1016/j.jcjd.2018.04.004. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30061044/
  15. Maideen, N. M., Jumale, A., & Balasubramaniam, R. (2017). Drug interactions of metformin involving drug transporter proteins. Advanced Pharmaceutical Bulletin, 7(4), 501-505. doi:10.15171/apb.2017.062. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788205/ 
  16. Markowicz-Piasecka, M., Huttunen, K. M., Mateusiak, Ł, Mikiciuk-Olasik, E., & Sikora, J. (2017). Is metformin a perfect drug? Updates in pharmacokinetics and pharmacodynamics. Current Pharmaceutical Design, (23), 2532-2550. doi:10.2174/1381612822666161201152941. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27908266/ 
  17. McCreight, L. J., Bailey, C. J., & Pearson, E. R. (2016). Metformin and the gastrointestinal tract. Diabetologia, (59), 426-435. doi:10.1007/s00125-015-3844-9. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742508/ 
  18. Misbin, R. I. (2004). The phantom of lactic acidosis due to metformin in patients with diabetes. Diabetes Care, 27(7), 1791-1793. doi:10.2337/diacare.27.7.1791. Retrieved from https://care.diabetesjournals.org/content/27/7/1791 
  19. National Library of Medicine. (2018). DailyMed: Glucophage – metformin hydrochloride tablet, film coated; Glucophage XR – metformin hydrochloride tablet, extended release. Retrieved Nov. 10, 2020, from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4a0166c7-7097-4e4a-9036-6c9a60d08fc6 
  20. Provilus, A., Abdallah, M., & McFarlane, S. I. (2011). Weight gain associated with antidiabetic medications. Therapy, 8(2), 113-120. doi:10.2217/THY.11.8. Retrieved from https://www.openaccessjournals.com/articles/weight-gain-associated-with-antidiabetic-medications.pdf 
  21. Song, I. H., Zong, J., Borland, J., Jerva, F., Wynne, B., Zamek-Gliszczynski, M. J., et al. (2016). The effect of dolutegravir on the pharmacokinetics of metformin in healthy subjects [Abstract]. Journal of Acquired Immune Deficiency Syndromes, 72(4), 400-407. doi:10.1097/QAI.0000000000000983. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935531/ 
  22. Stang, M. (1999). Incidence of lactic acidosis in metformin users [Abstract]. Diabetes Care, 22(6), 925-927. doi:10.2337/diacare.22.6.925. Retrieved from https://pubmed.ncbi.nlm.nih.gov/10372243/ 
  23. Tahrani, A. A., Varughese, G. I., Scarpello, J. H., & Hanna, F. W. (2007). Metformin, heart failure, and lactic acidosis: Is metformin absolutely contraindicated? BMJ, 335(7618), 508-512. doi:10.1136/bmj.39255.669444.AE. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971167/ 
  24. U.S. Department of Health and Human Services and U.S. Department of Agriculture (USDA). 2015 – 2020 Dietary Guidelines for Americans. 8th Edition. 2015. Available at https://health.gov/our-work/nutrition-physical-activity/dietary-guidelines/previous-dietary-guidelines/2015