Metformin prevents metabolic side effects during systemic glucocorticoid treatment.

Objectives: Patients receiving glucocorticoid treatment are prone to develop metabolic complications. In preclinical studies, metformin prevented the development of the metabolic syndrome during glucocorticoid excess. We herein investigated the metabolic effect of metformin during glucocorticoid treatment in non-diabetic patients.

Methods: In a double-blind, placebo-controlled trial, patients starting glucocorticoid treatment (prednisone, prednisolone or methylprednisolone) for four weeks were randomised to concomitantly receive metformin (850 mg once daily for one week followed by 850 mg twice daily for three weeks) or placebo. All patients underwent a standardised oral glucose tolerance test at baseline and after four weeks. The primary endpoint was change in the 2-h area under the curve (AUC) of glucose during the oral glucose tolerance test between baseline and four weeks.

Results: 29 of 34 randomised non-diabetic patients completed the trial (17 metformin and 12 placebo). In patients allocated to placebo, median glucose 2-h AUC increased from baseline to four weeks (836 (IQR 770-966) to 1202 (1009-1271) mmol/L per min; P = 0.01). In contrast, glucose levels remained similar to baseline in the metformin group (936 (869-1003) to 912 (825-1011) mmol/L per min; P = 0.83). This change within four weeks was different between both groups (P = 0.005). Glucocorticoid equivalent doses were similar in both groups (placebo: 980.0 (560.0-3259.8) mg/28 days; metformin: 683.0 (437.5-1970.5) mg/28 days; P = 0.26).

Conclusions: In this first randomised controlled trial of metformin targeting metabolic complications in patients needing glucocorticoid therapy, we observed a beneficial effect of metformin on glycaemic control. Metformin thus seems to be a promising drug for preventing metabolic side effects during systemic glucocorticoid treatment.