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

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 [Cl]) was 75.3% (68.8%-81.7%; n=13) and the proportion of adherent patients (95% Cl) was 67.9% (59.6%-76.3%; n=12). The discontinuation rate (95% Cl) 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% Cl) of 56.2% (46.1%-66.3%; n=6), while discontinuation estimates ranged from 9.9% to 60.1%, with a mean (95% Cl) 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.