Pharmacological management of youth with type 2 diabetes and diabetic kidney disease: a comprehensive review of current treatments and future directions

Introduction: Diabetic kidney disease (DKD) is a leading cause of mortality in people with type 2 diabetes (T2D), and over 50% of individuals with youth-onset T2D will develop DKD as a young adult. Diagnosis of early-onset DKD remains a challenge in young persons with T2D secondary to a lack of available biomarkers for early DKD, while the injuries may still be reversible. Furthermore, multiple barriers exist to initiate timely prevention and treatment strategies for DKD, including a lack of Food and Drug Administration approval of medications in pediatrics; provider comfort with medication prescription, titration, and monitoring; and medication adherence. Areas covered: Therapies that have promise for slowing DKD progression in youth with T2D include metformin, renin-angiotensin-aldosterone system inhibitors, glucagon-like peptide-1 receptor agonists, sodium glucose co-transporter 2 inhibitors, thiazolidinediones, sulfonylureas, endothelin receptor agonists, and mineralocorticoid antagonists. Novel agents are also in development to act synergistically on the kidneys with the aforementioned medications. We comprehensively review the available pharmacologic strategies for DKD in youth-onset T2D including mechanisms of action, potential adverse effects, and kidney-specific effects, with an emphasis on published pediatric and adult trials. Expert opinion: Large clinical trials evaluating pharmacologic interventions targeting the treatment of DKD in youth-onset T2D are strongly needed.