title: Metformin prevents metabolic side effects during systemic glucocorticoid treatment.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of EndocrinologyDiabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Seelig
authors.affiliation: Department of EndocrinologyDiabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Meyer
authors.affiliation: Department of EndocrinologyDiabetology and Metabolism, University Hospital Basel, Basel, Switzerland.|Max-Planck-Institute for Metabolism ResearchCologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.affiliation: Department of EndocrinologyDiabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Nigro
authors.affiliation: Division of EndocrinologyDiabetology and Metabolism, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Bally
authors.affiliation: Department of EndocrinologyWilliam Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Ida
authors.initials: I
authors.lastname: Pernicova
authors.affiliation: Division of EndocrinologyDiabetology and Metabolism, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.affiliation: Division of EndocrinologyDiabetology and Metabolism, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.affiliation: Department of EndocrinologyWilliam Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Korbonits
authors.affiliation: Department of EndocrinologyDiabetology and Metabolism, University Hospital Basel, Basel, Switzerland.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D008687:Metformin; D011239:Prednisolone; D011241:Prednisone; D008775:Methylprednisolone