Glycemic effectiveness and medication adherence with fixed-dose combination or coadministered dual therapy of antihyperglycemic regimens: a meta-analysis

OBJECTIVES: To compare effects of fixed-dosed combinations (FDCs) and coadministered dual therapy (CDT) of antihyperglycemic agents on glycemic control (i.e., HbA(1c)) and medication adherence. METHODS: A systematic literature review and meta-analysis were performed to compare the HbA(1c) response and medication adherence between the two drug regimens. Selected articles were limited to studies that compared equivalent drug components within FDC and CDT. Searches used PubMed, Embase, Web of Knowledge, and Cochrane databases. The search results were independently screened and reviewed by two authors (SH, KI). Of the 1246 identified abstracts, 152 articles were reviewed, and ten met the inclusion criteria. Results were extracted and pooled in a meta-analysis, using a random-effects model. Cohort comparisons were described as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: The ten articles that met the inclusion criteria had a total study size of 70,573 patients. Four articles reported HbA(1c) results, which had a total of five cohort comparisons of FDC and CDT use. The meta-analysis revealed a significantly greater HbA(1c) reduction with FDC (MD = -0.53% [95% CI: -0.78, -0.28]; p < 0.0001). Eight studies evaluated medication adherence (measured as medication possession ratio [MPR]). Of the eight studies reporting MPR results, a total of 12 cohort comparisons were made and were further divided into three subgroups based on comparison types. Five comparisons described MPR for FDC versus CDT cohorts, with significantly higher MPR with FDC (MD = 8.6% [95% CI: 1.6, 15.6]; p = 0.0162]). Four comparisons examined patients who switched from monotherapy to FDC or CDT, with higher MPR for patients who switched to FDC (MD = 7.7% [95% CI: 5.7, 9.6]; p < 0.0001). Three comparisons described results for patients who switched from CDT to FDC or stayed on CDT, with higher MPR for patients who switched to FDC (MD = 5.0% [95% CI: 3.1, 6.8]; p < 0.0001). LIMITATIONS: A limited number of published studies were available for this meta-analysis and all of those included were observational studies. There was heterogeneity between studies in the statistical methods used to control for confounding variables and differing population characteristics. CONCLUSIONS: In a meta-analysis, use of FDCs with antihyperglycemic agents was associated with lower HbA(1c) and higher MPR values compared to CDT use in patients with type 2 diabetes.