Long-Term Clinical Outcomes of Oral Antidiabetic Drugs as Fixed-Dose Combinations: A Nationwide Retrospective Cohort Study

Objectives: Patients with type 2 diabetes often require more than one medication for glycemic control. Although single pill fixed-dose combinations (FDC) might improve adherence, its impact on clinical outcomes remains unclear. We compared treatment patterns and clinical outcomes of FDC and two-pill combination (TPC) therapies using real-world data. Methods: : We conducted a nationwide retrospective cohort study using South Korea’s healthcare database (2002–2015). We identified two cohorts of incident patients with type 2 diabetes who initiated FDC or TPC therapy within 4 months of their first prescription for metformin or sulfonylurea. We examined persistence and adherence patterns and the clinical outcome of a composite endpoint of death or hospitalization for acute myocardial infarction, heart failure, or stroke and compared the differences in treatment patterns and clinical outcomes using Cox models. Results: : Of 5,143 and 10,974 patients who initiated FDC and TPC therapy, respectively, we identified 5,143 patient pairs after propensity score matching. The FDC group exhibited greater median time to treatment discontinuation (163 versus 146 days), and proportion of days covered (PDC) at 12 months (mean 0.60 versus 0.57, P < 0.0001) and at 24 months (0.53 versus 0.51, P=0.014) than the TPC group. The FDC group, compared with the TPC group, had reduced risks of the composite clinical outcome (hazard ratio 0.74, 95% confidence intervals 0.57–0.95) and hospitalization for stroke (0.68, 0.49–0.94). Conclusion: FDC therapy may provide favorable cardiovascular benefits, especially reducing the risk of hospitalization for stroke, and have better medication adherence among patients with type 2 diabetes.