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ObjectiveType 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs.MethodsSearches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses.ResultsA total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs.ConclusionsThe top 10 treatments of type 2 diabetes in children and adolescents aged 10–17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide–2 mcg, sitagliptin+metformin, linagliptin–5 mg, linagliptin–1 mg, metformin, and exenatide–5/10 mcg.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.