Real-world treatment escalation from metformin monotherapy in youth-onset Type 2 diabetes mellitus: A retrospective cohort study.

Abstract

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. To investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with Type 2 diabetes in clinical practice. Commercially-insured patients with incident youth-onset (10-18 years) Type 2 diabetes initially treated with metformin only. Retrospective cohort study using a patient-level medical claims database with data from 2000 to 2020. 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, complications, and metformin adherence (medication possession ratio ≥ 0.8). The cohort included 829 (66% female; median age at diagnosis 15 years; 19% Hispanic, 17% Black) patients, with median 2.9 year follow-up after metformin initiation. One-quarter underwent treatment escalation (n=207; 88 to insulin, 164 to non-insulin antihyperglycemic). Younger patients were more likely to have insulin prescribed prior to other antihyperglycemics. Age at diagnosis (HR 1.14, 95% CI 1.07-1.21), medication adherence (HR 4.10, 95% CI 2.96-5.67), Hispanic ethnicity (HR 1.83, 95% CI 1.28-2.61), and diabetes-related complications (HR 1.78, 95% CI 1.15-2.74) were positively associated with treatment escalation. In clinical practice, treatment escalation for pediatric Type 2 diabetes differs with age. Off-label use of non-insulin antihyperglycemics occurs, most commonly among older adolescents.