Liraglutide Versus Exenatide Once Weekly: Persistence, Adherence, and Early Discontinuation
Introduction
The discovery of a greater insulin response after oral versus intravenous glucose administration is known as the “incretin effect” and is attributed to the secretion of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide hormones by the small intestine.1 This finding has led to the design of incretin-based therapies: oral dipeptidyl peptidase-4 (DPP-4) inhibitors (such as sitagliptin and linagliptin) and injectable GLP-1 receptor agonists.1 The GLP-1 receptor agonist class includes exenatide BID, liraglutide once daily (QD), or exenatide, albiglutide, and dulaglutide once weekly (QW). Currently, there are 3 QW–, 1 BID–, and 1 QD–approved GLP-1 receptor agonists in the United States (exenatide QW [2012], albiglutide [2014], dulaglutide [2014], exenatide BID [2005], and liraglutide [2008]). At the time of this study, exenatide BID, exenatide QW, and liraglutide were the only approved GLP-1 receptor agonists.
Head-to-head randomized, controlled studies have shown the superior efficacy of liraglutide, exenatide QW, and dulaglutide compared with exenatide BID.2, 3, 4 Head-to-head randomized, controlled comparisons with liraglutide have further shown that dulaglutide is the only approved GLP-1 receptor agonist to demonstrate noninferiority to liraglutide,5 whereas exenatide QW, albiglutide, and exenatide BID have not demonstrated noninferiority to liraglutide.6, 7, 8
Treatment adherence in patients with type 2 diabetes (T2D) may be diminished due to complicated treatment regimens, medication costs, and tolerability issues. In general, fewer doses of medication per day are associated with better adherence to medication for T2D treatment.9, 10, 11, 12, 13 In an observational naturalistic study, patients initiating exenatide QW had slightly better adherence compared with those initiating exenatide BID or liraglutide.14 There have been few observational real-world comparisons of daily and weekly dosing due to the relatively recent availability of longitudinal data on the first approved weekly GLP-1 receptor agonist, exenatide QW.
This paper examines potential differences in observed persistence and adherence related to QD versus QW dose frequency, taking into account the influences of patient selection, treatment history, and different definitions of persistence and adherence among GLP-1 receptor agonist-treated patients using liraglutide and exenatide QW.
Section snippets
Methods
This retrospective observational study used insurance claims data to compare patients receiving exenatide QW or liraglutide. Data used for the analysis were derived from the Truven Health MarketScan* 2008 to 2013 Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Databases. These databases represent the health services of ~195 million employees, dependents, and retirees in the United States
Results
Before executing propensity score matching, the exenatide QW cohort included 13,274 patients and the liraglutide cohort included 31,675 patients (Figure 1). Baseline characteristics before propensity matching are provided in Table I. Several variables showed statistical significance (P ≤ 0.0001) between cohorts. This observation may be attributed to the large sample size. The variables that showed the greatest differences between cohorts were previous exenatide BID use (27% vs 9% for exenatide
Discussion
The results of this retrospective analysis show that depending on the method of analysis, slight differences in persistence and adherence rates of patients receiving a QW GLP-1 receptor agonist, exenatide, versus patients receiving a QD GLP-1 receptor agonist, liraglutide, may be observed. Overall, both measures analyzed provided similar results. The persistence results were similar to those observed by Divino et al.,17 and the adherence results were similar to those observed by Johnston et al.
Conclusions
This study is the first examination of early GLP-1 receptor agonist persistence and adherence conducted in a broader patient real-world cohort of GLP-1 receptor agonist users who were not GLP-1 receptor agonist naïve at their index episode. Its findings suggest that PDC metrics may be more robust and appropriate to studying GLP-1 receptor agonist adherence than are gap-based persistence metrics given potential device-driven differences in patient control over daily dosing. Furthermore, this
Conflicts of Interest
All authors are current or former employees of Eli Lilly and Company and own stock in the company. This research was funded and supported by Eli Lilly and Company. Eli Lilly and Company assisted with the design of the study, interpretation of the results, and development of the manuscript.
Acknowledgments
The authors thank Oralee Varnado for writing assistance. All authors have approved the final article. Eli Lilly and Company provided funding. M. Yu and J. Xie participated in the design of the study and the collection, analysis, and interpretation of the data. S. Kabul and R. W. Swindle participated in the design of the study and interpretation of the data. L. F. Lando participated in the interpretation of the data. All authors critically reviewed and revised the manuscript.
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