A Cochrane review included 2 studies with a total of 60 subjects investigating the effect of metformin added to insulin therapy for 3 months in adolescents with poorly controlled type 1 diabetes. Meta-analysis was not possible due to the clinical and methodological heterogeneity of data. In one study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P < 0.035) after 3 months of therapy. The second study showed a change of mean HbA1c of -0.9% in the metformin group compared to - 0.3% in the placebo group, after 3 months of metformin therapy. Improvement in insulin sensitivity, body weight or serum lipids were not seen in either study. However, one study showed a decrease in insulin dosage by 10%.
The evidence related to side-effects was conflicting. The metformin group experienced more side effects compared to the placebo group in one study (73% versus 47%) in the form of hypoglycaemia and gastrointestinal upset, while the opposite was demonstrated in the second study with less side-effects in metformin compared to the placebo group (19% versus 43%). No data on patient-oriented outcomes like health-related quality of life, all-cause mortality or morbidity are currently available.
Comment: The quality of evidence is downgraded by study quality (inadequate intention-to-treat adherence), by inconsistency (heterogeneity in interventions and outcomes) and by imprecise results (limited study size for each comparison).