Diabetes-induced hypomagnesemia is not modulated by metformin treatment in mice

Approximately 30% of patients with type 2 diabetes mellitus (T2D) have hypomagnesemia (blood magnesium (Mg²⁺) concentration <0.7 mmol/L). In T2D patients, treatment with metformin is associated with reduced blood Mg²⁺ levels. To investigate how T2D and metformin affect Mg²⁺ homeostasis db/m and db/db mice were treated with metformin or placebo. Mice were housed in metabolic cages to measure food and water intake, and to collect urine and feces. Serum and urinary Mg²⁺ concentrations were determined and mRNA expression of magnesiotropic genes was determined in kidney and distal colon using RT-qPCR. Db/db mice had significantly lower serum Mg²⁺ levels than db/m mice. Mild hypermagnesuria was observed in the db/db mice at two weeks, but not at four weeks. Metformin-treatment had no effect on the serum Mg²⁺ concentration and on the urinary Mg²⁺ excretion. Both in kidney and distal colon of db/db mice, there was a compensatory upregulation in the mRNA expression of magnesiotropic genes, such as transient receptor potential melastatin 6 (Trpm6), whereas metformin treatment did not affect gene expression levels. In conclusion, we show that T2D causes hypomagnesemia and that metformin treatment has no effect on Mg²⁺ homeostasis in mice.