Adherence in initiators of combination therapy among drug-naïve patients with type 2 diabetes: A real-world study using group-based trajectory model

Background: Recent clinical trial data suggested that early use of combination therapy among patients with diabetes has a more durable effect on glycemic control. However, the complexity of multidrug regimens associated with early use of combination therapy makes adherence more challenging, and combination therapy adherence is often inadequately captured. Objectives: This study aimed to assess the adherence trajectories of initial combination therapy users during the first year of antidiabetic treatment initiation. Methods: A retrospective study using Merative MarketScan research databases (2017-2019). Drug-naïve patients with type 2 diabetes (T2D) who received initial combination therapy and were continuously enrolled in commercial or Medicare insurance plans were identified. Patients who received 2 distinct antidiabetic medications within 30 days or on the same date were identified as initial combination therapy users. Adherence was measured within 1 year after the index date using the proportion of days covered. Group-based trajectory model (GBTM) was used to identify distinct longitudinal adherence patterns of combination therapy users. A multinomial regression model was performed to examine predictors associated with nonadherence trajectories. Results: A total of 116,597 drug-naïve patients with T2D were identified, of whom 14,118 (12.1%) initiated combination therapy. GBTM with 4 distinct trajectories of adherence was selected: adherent (30.5%), gradual decline (21.6%), gaps in adherence (21.2%), and rapid decline (26.7%). Overall, 71% of patients followed a nonadherent trajectory. The multinomial logistic regression model assessed that patients with health maintenance organization versus comprehensive plans were more likely to experience rapid decline, gradual decline, and gaps in adherence. Patients aged 55-64 versus 18-34 years were less likely to experience rapid decline in adherence, gradual decline in adherence, and gaps in adherence. Conclusion: Approximately 70% of patients with T2D who initiated combination therapy followed nonadherent trajectories during the first year of treatment. For initial combination therapy users, targeted interventions are needed to enhance suboptimal adherence.