Regimen simplification and medication adherence: Fixed-dose versus loose-dose combination therapy for type 2 diabetes

Abstract

Background Suboptimal patient adherence to pharmacological therapy of type 2 diabetes may be due in part to pill burden. One way to reduce pill burden in patients who need multiple medications is to use fixed-dose combinations. Our study aimed to compare the effects of fixed-dose combination versus loose-dose combination therapy on medication adherence and persistence, health care utilization, therapeutic safety, morbidities, and treatment modification in patients with type 2 diabetes over three years. Methods Using administrative data, we conducted a retrospective controlled cohort study comparing type 2 diabetes patients who switched from monotherapy to either a fixed-dose combination or a loose-dose combination. Adherence was assessed as the primary endpoint and calculated as the proportion of days covered with medication. After using entropy balancing to eliminate differences in observable baseline characteristics between the two groups, we applied difference-in-difference estimators for each outcome to account for time-invariant unobservable heterogeneity. Results Of the 990 type 2 diabetes patients included in our analysis, 756 were taking a fixed-dose combination and 234 were taking a loose-dose combination. We observed a statistically significantly higher change in adherence (year one: 0.22, p<0.001, year two: 0.25, p<0.001, and year three: 0.29, p<0.001) as well as higher persistence and a smaller change in the number of drug prescriptions in each of the three years in the fixed-dose combination group compared to the loose-dose combination group. The differences were most pronounced in patients who were poorly adherent, had a high pill burden, or did not have a severe concomitant disease. Conclusion Our results indicate that taking a fixed-dose combination can lead to a significant improvement in adherence to pharmacological therapy of type 2 diabetes compared to a loose-dose combination. In particular, these findings suggest that reducing pill burden may improve disease management among patients with more complex medication demand and patients who have demonstrated poor medication adherence.

Long‐term clinical outcomes of oral antidiabetic drugs as fixed‐dose combinations: A nationwide retrospective cohort study

“…Our findings are generally consistent with those of previous studies that showed a positive association between FDC therapy and adherence and persistence 11,12,21‐24 . A meta‐analysis conducted by Bangalore et al revealed that FDC therapy improved medication non‐compliance by 26% (pooled relative risk, 0.74; 95% CI 0.69‐0.80; P < .0001) when compared with a free‐drug combination 21 .…”

“…29 Another study that compared drug compliance and morbidities over a 3-year period failed to detect a statistically significant difference in morbidities between TPC and FDC. 11 Our findings for the composite clinical outcome and hospitalization for stroke associated with FDC versus TPC revealed statistically significant differences in favour of the FDC group. The FDC group had 2.55 and 1.84 fewer events per 1000 person-years, respectively, than the TPC group (Table 4).…”

“…However, there was no significant difference in mortality rates between the FDC and TPC groups (Figure S3), which is consistent with the findings of a previous study. 11 Hence, because FDC therapy was associated with a reduced risk of adverse clinical outcomes and improved medication adherence, patients with type 2 diabetes could experience greater clinical benefits with FDC therapy than with TPC therapy.…”

“…11,12,[21][22][23][24] A meta-analysis conducted by Bangalore et al revealed that FDC therapy improved medication noncompliance by 26% (pooled relative risk, 0.74; 95% CI 0.69-0.80; P < .0001) when compared with a free-drug combination 21. Another study by Barner found 9% improvement in medication adherence, but did not compare it with an active comparator, making it difficult toT A B L E 3 a Student's t-test was used.…”

“…Furthermore, poor adherence is associated with poor glycemic control and subsequently increased morbidity, mortality, and health care costs [6,[8][9][10]. To ease the complexity of treatment for type 2 diabetes, FDC may enhance medication adherence and thus glycemic control by simplifying the treatment regimen for patients with type 2 diabetes [4,11,12]. Therefore, there is a clinical need to better elucidate the role of FDCs in patients with type 2 diabetes in routine care by comparing the treatment patterns of adherence and persistence and clinical outcomes versus TPCs using real-world data.…”