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Is Depression Linked to Metformin for Diabetes?

A possible vitamin B12 deficiency could explain depression linked to metformin for blood sugar control. An additional supplement might help.
Metformin prescription pills with identification numbers on blue background ,image of a

Doctors and patients both may have a hard time determining when a new health concern is actually a side effect. That’s especially difficult when you don’t find the problem on any official list of drug adverse effects. As a result, one reader ended up wondering, “Is my depression linked to metformin?”

How Is Depression Linked to Metformin?

Q. I was recently prescribed metformin to control blood sugar. When the dosage increased from one to two times a day, I began to have serious depression.

I had experienced depression many years earlier. Then, the cause was hypothyroidism; after two weeks on Synthroid, I was a “new person.” Consequently, I knew that this wasn’t just random sadness.

I treated myself as a guinea pig, starting and stopping the medicine three times just to be sure that metformin was really the cause. Each time, it took longer to feel normal again. When I reported this to my internist, she wasn’t aware that this was a side effect.

I have found that increasing my dose of B vitamins, especially vitamin B12, helps the depression somewhat. I’ve had chronic trouble getting enough B12 since I was a teenager, but my doctor monitors my levels.

Metformin and Vitamin B12 Deficiency:

A. Metformin is the most commonly prescribed diabetes drug in the world. It works well, but it can cause vitamin B12 deficiency (Diabetes & Metabolism, Nov. 2016). 

Low vitamin B12 levels have been associated with depression (Fortify Your Life: Your Guide to Vitamins, Minerals and More). Other symptoms of B12 deficiency include fatigue, numbness and tingling, sore tongue, palpitations and shortness of breath.

You might ask your doctor to request a methylmalonic acid (MMA) test in addition to your serum B12 blood test. High levels of MMA point to low levels of vitamin B12. 

Ask your doctor to help you find the right dose of vitamin B12 to overcome depression linked to metformin. You shouldn’t have to feel severely depressed in order to control your blood sugar.

Learn More:

You may want to read more about diabetes or depression to prepare for your conversation with your health care provider. We suggest our eGuides to Managing Diabetes and Dealing with Depression for further information. If you have had a similar experience, please feel free to share it in the comment section.

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About the Author
Terry Graedon, PhD, is a medical anthropologist and co-host of The People’s Pharmacy radio show, co-author of The People’s Pharmacy syndicated newspaper columns and numerous books, and co-founder of The People’s Pharmacy website. Terry taught in the Duke University School of Nursing and was an adjunct assistant professor in the Department of Anthropology. She is a Fellow of the Society of Applied Anthropology. Terry is one of the country's leading authorities on the science behind folk remedies. .
Fortify Your Life: Your Guide to Vitamins, Minerals, and More

Fortify Your Life gives you the evidence-based information you need to decide whether you need a supplement and which format and dose would be best.

Fortify Your Life: Your Guide to Vitamins, Minerals, and More
  • Chapman LE et al, "Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis." Diabetes & Metabolism, Nov. 2016. DOI: 10.1016/j.diabet.2016.03.008
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I just saw an article, “Drug Effects on the Thyroid” by Henry B. Burch of NIH, that indicated in the Appendix, if I recall correctly, that Metformin reduces thyroid stimulating hormone (TSH). N Engl J Med 2019;381:749-61. This would explain why thyroid medication would help. Although the New England Journal of Medicine usually charges (plenty) for articles, you can get a free subscription to its newsletter online and receive 3 free articles per month to read and download.

After taking Metformin for 3 years, I developed feelings of persecution. I was determined everyone was out to get me. It wasn’t till after coming off Metformin that I discovered that was listed as a possible side effect. Never thought about that causing my problem. Recovered slowly after stopping the Metformin.

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