UCI-Led Study Investigates “Effect of Metformin Use on Vitamin B12 Deficiency Over Time”

In “Effect of Metformin Use on Vitamin B12 Deficiency Over Time (EMBER): A Real-World Evidence Database Study,” UC Irvine faculty and students explored the relationship between a common type 2 diabetes drug and vitamin B12 deficiency, along with related complications. The study was led by Dr. Aryana Sepassi, with Dr. Keri Hurley, Dr. Joyce Lee, and Dr. Sarah McBane contributing. Data science undergraduate students Chuong Hoang Vu, Nhat Minh Dao, and Lam Chau Tran also worked on the study as part of their capstone course.

Published by Endocrine Practice, the study looks into how the use of metformin may lead to vitamin B12 deficiency in people with type 2 diabetes. Metformin is generally the standard for type 2 diabetes treatment and is often used over a long period of time, with some patients taking metformin throughout their life. Millions of people with type 2 diabetes take metformin.

“We found that patients with a record of metformin use of longer than 4 years had a 41% increased risk of vitamin B12 deficiency. Metformin also increased the risk of borderline deficiency,” said Dr. Sepassi. “Additionally, there was a 5% increased risk of deficiency with each additional year of metformin use beyond 4 years.”

The link between metformin use and B12 deficiency exposes a potential alternative cause of neuropathy in people with type 2 diabetes. Neuropathy, or damage to the nerves in the extremities and cardiovascular system, can cause people to experience numbness and pain in the feet and hands, a complication that is often associated with type 2 diabetes. While both diabetes and vitamin B12 deficiency can cause neuropathy, understanding which of these issues has led to the complication is crucial.

Dr. Sepassi stated, “For the most part, these complications are assumed to be attributable to diabetes when they are diagnosed, so our results provide additional evidence to speak to the importance of assessing for vitamin B12 deficiency where supplementation can prevent progression or even reverse neuropathy to some degree.”

The study further explains the value of identifying vitamin B12 deficiency in people with type 2 diabetes, outlining how neuropathy caused by vitamin B12 deficiency can often be irreversible. By linking neuropathy to diabetes rather than vitamin B12 deficiency caused by metformin use, patients can be put at risk.

The researchers plan to continue their analysis of this issue by specifically inspecting the link between metformin use and neuropathy. As shared by Dr. Sepassi, they hope to answer the question: “Do participants with long-standing metformin use have an increased risk of developing neuropathic complications?”