Comparison of the Efficacy and Safety of Metformin-Based Combination Therapy Versus Metformin Alone in Children and Adolescents With Type 2 Diabetes Mellitus: A Meta-Analysis

The aim of this meta-analysis is to synthesize and critically evaluate the available evidence on the comparison of the efficacy and safety of metformin-based combination therapy versus metformin alone in children and adolescents with type 2 diabetes mellitus (T2DM). We performed the present meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Eligible studies were identified using electronic searches for randomized controlled trials (RCTs) using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrial.gov from inception to 31 January 2023. The outcomes examined in this meta-analysis included change from baseline in glycated hemoglobin (HbA1C) (%), fasting plasma sugar (FPG) (mg/dl), and the number of individuals experiencing adverse events. Three studies met the criteria and were included in the meta-analysis. The reduction of HbA1C was significantly higher in metformin-based combination therapy (MD: -1.19, 95% CI: -2.05, -0.33, p-value: 0.007). No significant difference was reported between patients randomized in metformin-based combination therapy and metformin alone (MD: -18.67, 95% CI: -50.17, 12.84, p-value: 0.25). In conclusion, the present meta-analysis found that the reduction in HbA1C was significantly higher in patients receiving metformin-based combination therapy compared to metformin alone. No significant difference was found between the two groups in terms of the change in fasting plasma glucose (FPG) from the baseline. In relation to safety, no significant difference was found in the incidence of adverse events and serious adverse events between the two groups.