Pros and Cons of Early Treatment with GLP-1 Receptor Agonist and SGLT-2 Inhibitors for Youth with Type 2 Diabetes: A Narrative Review

The incidence of youth-onset type 2 diabetes (Y-T2D) has been increasing over the last two decades in line with the growing rate of childhood obesity. Prior to 2019, the only United States Food and Drug Administration (FDA)-approved therapies for Y-T2D were metformin and insulin, and the current consensus guidelines recommend these therapies as first-line treatment. While metformin has a known safety profile and early efficacy for glycemic control, it has not been shown to prevent β-cell dysfunction or exogenous insulin requirements. Insulin is effective in treating hyperglycemia, but can result in hypoglycemia and further weight gain, worsening insulin resistance in Y-T2D. Furthermore, longitudinal data from participants treated early in their disease course with metformin and insulin demonstrate a cumulative incidence of at least one diabetes complication in most participants within 13 years of diagnosis. Over the last five years, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) have been added to the management toolbox for Y-T2D. However, further research is needed to determine the best timing and use for these medications for Y-T2D. The goal of this narrative review is to describe the current evidence for treatment with SGLT-2is and GLP-1RAs for Y-T2D within the first 1–2 years of the disease process.