Efficacy and Safety of SGLT2 Inhibitors in Pediatric Patients and Young Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: In recent decades, an increase in the incidence of type 2 diabetes mellitus (T2DM) in children and adolescents has been observed. Pediatric-onset T2DM differs from the adult-onset form, particularly regarding the durability of glycemic control and earlier appearance of complications. However, the scarcity of approved treatments and comprehensive studies on T2DM management in youth persists. Ongoing clinical trials seek to ascertain the efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients aged between 10 and 24 years with T2DM. Therefore, we aimed to perform a meta-analysis exploring the efficacy and safety of SGLT2i in pediatric patients and young adults with T2DM. Methods: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the efficacy and safety of SGLT2i in children, adolescents, and young adults with T2DM compared with placebo. Statistical analysis was performed using RevMan 5.4 and R statistical software 4.2.1. Heterogeneity was assessed with I² statistics. Results: We included three studies totaling 334 patients followed for 37.79 weeks. Reduction in HbA₁C (MD = -0.93; 95% CI = -1.36 to -0.49; p  < 0.0001; I²  = 0%) was significantly higher in SGLT2i group compared with placebo. The proportion of patients requiring rescue or discontinuation of study medication due to lack of efficacy was statistically lower in SGLT2i group compared with placebo (RR = 0.64; 95% CI = 0.43-0.94; p= 0.02; I²  = 0%). SGLT2i and placebo were similar in terms of any adverse event (RR = 1.10; 95% CI = 0.96-1.27; p= 0.17; I²  = 0%), serious side effects (RR = 1.06; 95% CI = 0.44-2.57; p=0.90; I²  = 0%), and individual adverse effects. Conclusion: In children, adolescents, and young adults with T2DM, SGLT2i appears to be effective and safe for glycemic control.