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

Abstract

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.

Key words::

• Antihyperglycemic therapy
• Compliance
• Diabetes
• Efficacy
• Meta-analysis

Transparency

Declaration of funding

The study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Declaration of financial/other relationships

S.H., K.I., M.J.D., Q.Z., and L.R. all declare that they are/were full-time employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ at the time of the analysis and may potentially own stock and/or hold stock options in the company.

Author contributions

S.H., K.I., M.J.D., Q.Z., and L.R. were involved in the concept and design of the study, data collection and/or analysis, and interpretation of the results. S.H. and M.J.D. drafted the article and all authors were involved in the critical revision and approval of the article. CMRO peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgment

We wish to acknowledge Asclepius JT LLC for their consultation in the data analysis of this manuscript, which was funded by Merck Sharp & Dohme, Corp.