Long-term treatment with metformin in type 2 diabetes and vitamin D levels: A post-hoc analysis of a randomized placebo-controlled trial

Aims To study the effects of metformin, as compared to placebo, on serum levels of vitamin D (25-hydroxyvitamin D [25(OH)D]) in patients with advanced type 2 diabetes. Materials and Methods In the HOME trial, a randomized placebo-controlled trial, 390 insulin-treated patients with type 2 diabetes were treated with 850 mg metformin or placebo thrice daily for 52 months. In a post-hoc analysis, we examined changes in the combined levels of 25(OH)D-2 and 25(OH)D-3 at 4 and 16 months during the study. Results Mean combined 25(OH)D at baseline was 68.2 nmoL/L (95% confidence interval [CI]: 65.5-71.1). In mixed model analysis, metformin, as compared to placebo, had no effect on 25(OH)D levels during 16 months (coefficient: 1.002 per month, multiplicative model; 95% CI: 0.998-1.006, P=.30). Metformin was associated with a small increase of 25(OH)D-2 (coefficient: 1.012 per month; 95% CI: 1.003-1.021, P=.008). However, 25(OH)D-2 is only a very small fraction (3%) of 25(OH)D. Seasonal variation had the biggest impact on 25(OH)D levels. Vitamin B12 levels were not associated with the levels of 25(OH)D. Conclusion Metformin had no effect on serum 25(OH)D during 16 months in the setting of a clinical randomized controlled trial in patients with type 2 diabetes. Our results show that metformin doesn't lead to vitamin D deficiency.