title: The use of metformin in type 1 diabetes: a systematic review of efficacy.
abstract: OBJECTIVE
  As adding metformin to insulin therapy has been advocated in type 1 diabetes, we conducted a systematic review of published clinical trials and clinical trial databases to assess the effects on HbA(1c), weight, insulin-dose requirement and adverse effects.
  
  
  METHODS
  We constructed evidence tables and fitted a fixed-effects model (inverse variance method) in order to assess heterogeneity between studies and give a crude measure of each overall treatment effect.
  
  
  RESULTS
  Of 197 studies identified, nine involved randomisation with informed consent of patients with type 1 diabetes to metformin (vs placebo or comparator) in either a parallel or crossover design for at least 1 week. We noted marked heterogeneity in study design, drug dose, age of participants and length of follow-up. Metformin was associated with reductions in: (1) insulin-dose requirement (5.7-10.1 U/day in six of seven studies); (2) HbA(1c) (0.6-0.9% in four of seven studies); (3) weight (1.7-6.0 kg in three of six studies); and (4) total cholesterol (0.3-0.41 mmol/l in three of seven studies). Metformin was well tolerated, albeit with a trend towards increased hypoglycaemia. Formal estimates of combined effects from the five trials which reported appropriate data indicated a significant reduction in insulin dose (6.6 U/day, p < 0.001) but no significant reduction in HbA(1c) (absolute reduction 0.11%, p = 0.42). No reported trials included cardiovascular outcomes.
  
  
  CONCLUSIONS
  Metformin reduces insulin-dose requirement in type 1 diabetes but it is unclear whether this is sustained beyond 1 year and whether there are benefits for cardiovascular and other key clinical outcomes.
authors.affiliation: Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
authors.forename: S
authors.initials: S
authors.lastname: Vella
authors.forename: L
authors.initials: L
authors.lastname: Buetow
authors.forename: P
authors.initials: P
authors.lastname: Royle
authors.forename: S
authors.initials: S
authors.lastname: Livingstone
authors.forename: H M
authors.initials: HM
authors.lastname: Colhoun
authors.forename: J R
authors.initials: JR
authors.lastname: Petrie
mesh_terms: D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin