BACKGROUND: Artificially sweetened beverages (ASBs) are commonly recommended as a substitute for sugar-sweetened beverages (SSBs) in dietary counseling. Childhood obesity, associated with comorbidities like type 2 diabetes (T2D), has risen alongside increased consumption of both SSBs and ASBs. Metformin, a common treatment for pediatric T2D, affects GDF-15, a hormone involved in weight regulation. This pilot study examines the impact of ASBs on the therapeutic effects of metformin in pediatric patients with obesity and prediabetes, focusing on growth differentiation factor 15 (GDF-15) as a potential mediator. METHODS: Forty-six children aged 10-21 years were randomized into two groups: one consuming non-sweetened beverages (USB) and the other consuming ASBs during a 12-week metformin intervention. RESULTS: While the USB group showed a greater decrease in the point estimate for mean BMI (-0.55 ± 1.49 USB vs. -0.23 ± 1.60 ASB) and an increase in the point estimate for mean GDF-15 (33.40 ± 58.34 in USB vs. 19.77 ± 85.87 in ASB), these differences were not statistically significant ( CONCLUSIONS: Additional studies are needed to fully elucidate the impact of non-nutritive sweeteners on metabolic health and treatment outcomes in pediatric obesity.