P-243: Effectiveness of metformin for the prevention of type 2 diabetes in children and adolescents with overweight or obesity: a systematic review and meta-analysis
N Derhami, N Wills, A Makhij, H Patrick, A Pourtousi, J Asfour, L McAlister, M Ybarra, T Jeronimo dos SantosAbstract
Introduction
Type 2 diabetes incidence is rising globally in youth. While lifestyle modification remains the cornerstone of prevention, adherence is often limited. Metformin has shown preventive efficacy in adults, but its role in pediatric populations remains uncertain.
Objectives
To evaluate the effectiveness of metformin, alone or combined with lifestyle interventions, in preventing type 2 diabetes in children and adolescents with overweight or obesity.
Methods
We conducted a systematic review (PRISMA; PROSPERO: CRD42024615622) searching PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library from inception to June 2025. Eligible studies included RCTs and prospective cohorts in individuals aged <18 years. The primary outcome was type 2 diabetes incidence; secondary outcomes included HbA1c, fasting glucose, 2-hour OGTT, HOMA-IR, and BMI. Data were extracted using a standardized framework and synthesized narratively due to heterogeneity.
Results
A total of 3,410 records were identified; 1,640 duplicates were removed. After screening, 139 full-text articles were assessed and 27 studies met inclusion criteria (follow-up 3–24 months) across 16 countries, primarily in North America and Europe, with fewer from middle-income settings such as Mexico, Thailand, Iran, and Turkey. No study was adequately powered to assess diabetes incidence. Metformin improved BMI in 20/27 studies and HOMA-IR in 17/27, primarily short-term. Glycemic effects were inconsistent: HbA1c improved in 6/27, fasting glucose in 9/27, and 2-hour OGTT in 7/27. Where lifestyle comparators were included, both groups improved with no consistent additional benefit from metformin.
Conclusions
No evidence supports metformin preventing type 2 diabetes in youth with overweight or obesity. While short-term improvements in BMI and insulin resistance are observed, glycemic effects are inconsistent. Long-term, adequately powered pediatric trials with diabetes incidence as a primary outcome are urgently needed.