A new study published in the Journal of Diabetes Investigation has shown that people with type 2 diabetes (T2DM) who take both metformin and proton pump inhibitors (PPIs) are more likely to develop a vitamin B12 deficiency compared to those using metformin alone. Since PPIs are commonly used to treat acid reflux—a condition frequently reported by people with diabetes—many patients may be taking both medications at the same time.
Researchers conducted a retrospective cohort study using a national health insurance database. They focused on adults newly diagnosed with T2DM who had been using metformin for at least four months. These patients were divided into two groups: those who used only metformin and those who used both metformin and a PPI. The study included 11,200 patients after matching both groups using propensity scores to reduce bias.
Vitamin B12 deficiency was identified either through diagnostic codes or by checking if patients were prescribed B12 supplements. Results showed that individuals taking both metformin and a PPI had an 18% higher risk of developing vitamin B12 deficiency compared to those taking metformin alone (adjusted hazard ratio, 1.18; 95% confidence interval, 1.02–1.35).
The findings suggest that combining these two common medications can increase the risk of a preventable nutrient deficiency.
• Metformin and PPIs are commonly used together in people with type 2 diabetes, especially for treating acid reflux symptoms.
• Using both drugs at the same time is linked to a significantly higher risk of vitamin B12 deficiency.
• In an extensive matched study of 11,200 patients, those using both drugs had an 18% increased risk compared to those on metformin alone.
• Vitamin B12 deficiency may cause various health issues, such as nerve problems and anemia.
• Regular monitoring of vitamin B12 levels is recommended in patients using both metformin and PPIs.
Jung C, Park S, Kim H. Concomitant use of metformin and proton pump inhibitors increases vitamin B12 deficiency risk in type 2 diabetes. J Diabetes Investig. 2025;16(6):1020-1027. doi:10.1111/jdi.70037
People with type 2 diabetes who take both metformin and proton pump inhibitors are more likely to develop a vitamin B12 deficiency compared to those using metformin alone.