Meta-analysis of studies examining medication adherence, persistence, and discontinuation of oral antihyperglycemic agents in type 2 diabetes

Abstract

Objective:

To estimate overall rates of adherence, persistence, and discontinuation for patients with type 2 diabetes mellitus (T2DM) prescribed oral antihyperglycemic agents (OAHAs) by combining results of published studies.

Research design and methods:

A systematic literature review was conducted to identify articles published in English over the last 10 years evaluating the use of OAHAs for the treatment of T2DM. Databases searched included PubMed/MEDLINE, EMBASE, and the Cochrane Library. Seventy studies reporting adherence, persistence or discontinuation were identified by two independent reviewers and 40 reported relevant endpoints for the analysis. Outcomes included: (1) mean adherence defined as the average medication possession ratio (MPR); (2) proportion of adherent patients (MPR ≥ 80%); (3) discontinuation; and (4) persistence. Adherence and persistence were reported in observational studies only. Discontinuation was examined separately in randomized controlled trials (RCTs) and observational studies. Meta-analyses were conducted using both fixed and random effects models. When meta-analysis was not appropriate for a given outcome, descriptive statistics were provided.

Results:

The pooled mean MPR (95% confidence interval [CI]) was 75.3% (68.8%–81.7%; n = 13) and the proportion of adherent patients (95% CI) was 67.9% (59.6%–76.3%; n = 12). The discontinuation rate (95% CI) in RCTs was 31.8% (17.0%–46.7%; n = 7). Persistence and discontinuation were not assessed via meta-analysis for observational studies due to the limited number of available studies and differences in outcome definitions. In these studies, persistence estimates ranged from 41.0% to 81.1%, with a mean (95% CI) of 56.2% (46.1%–66.3%; n = 6), while discontinuation estimates ranged from 9.9% to 60.1%, with a mean (95% CI) of 31.4% (17.6%–45.3%; n = 6).

Limitations:

Limitations include (1) the use of MPR as a proxy for adherence, (2) limited number of studies available, and (3) observed heterogeneity.

Conclusion:

The results of the analysis demonstrate that medication adherence, persistence, and discontinuation rates are suboptimal in patients with T2DM prescribed OAHAs.

Keywords: :

• Adherence
• Discontinuation
• Oral antihyperglycemic agents
• Persistence
• Type 2 diabetes

Transparency

Declaration of funding

This study was funded by Merck & Co. Inc, Kenilworth, NJ, USA.

K.I., L.R., V.M.R., K.T., and V.Z. were involved in the concept and design of the study. S.E.C. performed the data analysis, and K.I., S.E.C., V.Z., S.N.R., L.R., and K.T. were involved in the interpretation of the results. K.I. wrote the initial draft of the article, and all authors were involved in the critical revisions, discussions and approval of the article.

Declaration of financial/other relationships

K.I., S.N.R., L.R., and K.T. have disclosed that they are/were full-time employees of Merck & Co. Inc. at the time of the analysis and may potentially own stock and/or hold stock options in the company. S.E.C., V.M.R., and V.Z. have disclosed that they received research support from Merck & Co. Inc. for the conduct of this study.

CMRO peer reviewer 1 has disclosed that she has received grants from PCORI, NIH and Henry Ford Health System. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

Previous presentation: 2013 European Association for the Study of Diabetes Annual Meeting, 2013 World Diabetes Congress.