Abstract The association between change in glucose metabolism and change in skeletal muscle magnesium (Mg) concentration induced by antihypertensive treatment was evaluated in 37 patients with essential hypertension randomly treated with either lisinopril or bendrofluazide. Before and after 6 months of treatment, skeletal muscle biopsies were performed, glucose tolerance was determined by oral (OGTT) and intravenous glucose tolerance tests (IVGTT), and insulin sensitivity was assessed by the hyperinsulinemic euglycemic clamp technique. An inverse relationship was found between the treatment-induced change in fasting plasma glucose concentration and change in skeletal muscle Mg concentration (r = −0.39, P < .05). However, there was no significant correlation between skeletal muscle Mg content and either insulin sensitivity measured by the hyperinsulinemic euglycemic clamp test or glucose tolerance evaluated by IVGTT and OGTT. In conclusion, an increased circulating glucose concentration was correlated with a decreased Mg concentration in skeletal muscle during antihypertensive treatment. However, the Mg concentration in skeletal muscle did not significantly predict the insulin sensitivity or glucose tolerance.