The current meta-analysis provides evidence of a beneficial effect of a lifestyle intervention and/or drugs in children and adolescents living with obesity or overweight, consistent with a significant reduction in body fat—but not in BMI or waist circumference—an increase in circulating adiponectin and/or a reduction in serum insulin levels and diastolic blood pressure, and a trend towards a reduction of circulating leptin and glucose levels, as well as of the HOMA-IR. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.