Background: Due to high rates of comorbidities and rapid progression, youth with type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin. Objective: To investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with type 2 diabetes in clinical practice. Subjects: Commercially-insured patients with incident youth-onset (10-18 years) type 2 diabetes initially treated with metformin only. Methods: Retrospective cohort study using a patient-level medical claims database with data from 2000 - 2019. Frequency and order of treatment escalation to insulin and non-insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, and metformin adherence (medication possession ratio ≥0.8). Results: The cohort included 806 (66% female; median age at diagnosis 15 years; 19% Hispanic, 16% Black) patients, with median 3.0-year follow-up after metformin initiation. One-quarter underwent treatment escalation (n=198; 78 to insulin, 160 to non-insulin antihyperglycemic). Younger patients were more likely to have insulin as the initial or only antihyperglycemic prescribed. Age at diagnosis (HR 1.14, 95% CI 1.07-1.22), medication adherence (HR 3.77, 95% CI 2.71-5.23), and Hispanic ethnicity (HR 1.46, 95% CI 1.05-2.04) were positively associated with treatment escalation, but comorbidities were not associated. Conclusions: In clinical practice, treatment escalation for pediatric type 2 diabetes differs with age. Off-label use of non-insulin antihyperglycemics occurs and is most common among older adolescents. Disclosure M. Vajravelu: None. T. A. Hitt: None. S. Amaral: None. L. E. Katz: None. J. M. Lee: Advisory Panel; Self; GoodRx. A. Kelly: Consultant; Self; Vertex Pharmaceuticals Incorporated, vTv Therapeutics. Funding National Institutes of Health (K23DK125719-01, 5T32DK063688-17, R01DK110749, R01DK120886, R01HD091185, 5U01DK061230, UL1-TR000003, 2P30DK089503-11, R01HD074559-01-A1, UH3HD087979, R01DK115648, DK97830, UL1TR001878); Caswell Diabetes Institute at the University of Michigan
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