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

Abstract

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 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).

Results: 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.

Conclusions: 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.

Keywords: adolescent; insulin; medication adherence; metformin; type 2 diabetes mellitus.

FIGURE 1

Patient flow diagram, depicting number of, and reasons for, patients excluded from the cohort

FIGURE 2

Distribution of age at first prescription for insulin or non-insulin antihyperglycemic medication. The age distribution is narrowed and right-shifted for non-insulin anithyperglycemics as compared to insulin, demonstrating the tendency to prescribe non-insulin antihyperglycemics more frequently as patients age into young adulthood

FIGURE 3

Cumulative incidence curve depicting the proportion of patients with treatment escalation from metformin monotherapy within 5 years. Grey shaded areas represent 95% confidence intervals

FIGURE 4

Cumulative incidence curve depicting the proportion of patients with treatment escalation to (A) insulin, or (B) non-insulin antihyperglycemic within 5 years. Grey shaded areas represent 95% confidence intervals