AIMS/HYPOTHESIS: 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/ INTERPRETATION: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.
RCT Entities:
AIMS/HYPOTHESIS: 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/ INTERPRETATION: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: S S Soedamah-Muthu; J H Fuller; H E Mulnier; V S Raleigh; R A Lawrenson; H M Colhoun Journal: Diabetologia Date: 2006-01-24 Impact factor: 10.122
Authors: Susan P Laing; Anthony J Swerdlow; Lucy M Carpenter; Stefan D Slater; Andrew C Burden; Johannes L Botha; Andrew D Morris; Norman R Waugh; Wendy Gatling; Edwin A M Gale; Christopher C Patterson; Zongkai Qiao; Harry Keen Journal: Stroke Date: 2003-02 Impact factor: 7.914
Authors: Laura M Nally; Jennifer L Sherr; Michelle A Van Name; Anisha D Patel; William V Tamborlane Journal: Expert Rev Clin Pharmacol Date: 2019-05 Impact factor: 5.045