Type 2 diabetes is increasingly prevalent among children and adolescents with overweight or obesity, and although lifestyle interventions remain first-line preventive strategies, long-term adherence and effectiveness are often limited. Metformin has demonstrated efficacy in delaying type 2 diabetes onset in adults at high risk, but its preventive role in pediatric populations remains unclear. This systematic review and meta-analysis aims to evaluate the effectiveness of metformin, alone or in combination with lifestyle interventions, in preventing or delaying type 2 diabetes among children and adolescents with overweight or obesity. The protocol is registered in PROSPERO (CRD42024615622), MEDLINE (PubMed), Embase, Cochrane Library, Scopus, and Web of Science and will be searched from inception to June 2025. Eligible studies include randomized controlled trials, quasi-experimental studies, and prospective cohort studies involving individuals under 18 years of age. The primary outcome is incidence of type 2 diabetes, with secondary outcomes including fasting plasma glucose, HbA1c, insulin resistance, BMI z-score, adherence, and adverse events. Where appropriate, random-effects meta-analyses will be conducted. This review will synthesize current evidence on metformin for pediatric type 2 diabetes prevention and inform future preventive strategies and clinical decision-making.
Wills et al. (Sat,) studied this question.