The role of metformin in modulating cardiometabolic risk in obese pediatric populations with metabolic syndrome: A systematic review

Introduction: Obesity significantly increases the risk of developing cardiometabolic complications, which are precursors to cardiovascular diseases (CVD). In children and adolescents, metabolic dysfunctions such as insulin resistance, dyslipidemia, and hypertension are key contributors to early-onset cardiovascular risk. Metformin, a well-established antidiabetic agent, has shown potential benefits in addressing these metabolic imbalances. However, the long-term impact of metformin on cardiovascular outcomes in obese pediatric patients remains unclear. Aim: This systematic review aims to evaluate the effect of metformin on cardiometabolic parameters in obese children and adolescents with metabolic syndrome, focusing on insulin sensitivity, body mass index (BMI), blood pressure, and lipid profiles. Methods: A systematic review was conducted by searching databases including PubMed, Cochrane Library, Embase, and Web of Science. The inclusion criteria targeted randomized controlled trials (RCTs), cohort studies, systematic reviews, and meta-analyses published between 2004 and 2024. Pediatric patients aged 6-18 years with obesity and metabolic syndrome were included. The primary outcomes assessed were BMI, insulin sensitivity, lipid profiles, blood pressure, and cardiovascular outcomes. Results: A total of 23 studies, including 10 RCTs and 1 meta-analysis, were reviewed, involving 777 patients. Metformin demonstrated consistent improvements in insulin sensitivity and BMI in obese children and adolescents. Several studies reported modest reductions in BMI, improved insulin resistance, and better lipid profiles. However, variability in results was observed regarding long-term cardiovascular outcomes. While metformin reduced systolic blood pressure and carotid intimal-medial thickness (CIMT), the long-term impact on preventing major cardiovascular events remained inconclusive. Discussion: Metformin’s benefits on cardiometabolic risk factors in obese children are primarily attributed to its effects on insulin sensitivity, lipid metabolism, and inflammatory pathways. Its ability to activate AMP-activated protein kinase (AMPK) leads to improved metabolic profiles and reduced inflammation and is crucial for mitigating obesity-related cardiovascular risks. Despite these positive effects, the evidence for long-term prevention of cardiovascular events is limited and requires further exploration. Conclusions: Metformin offers significant short-term benefits in improving BMI, insulin sensitivity, and cardiometabolic parameters in obese children and adolescents. However, its long-term efficacy in preventing cardiovascular events remains uncertain. Further studies are necessary to establish its role in long-term cardiovascular protection in pediatric populations