21-OR: Real-World Treatment Escalation from Metformin Monotherapy in Youth-Onset Type 2 Diabetes Mellitus: A Retrospective Cohort Study

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.