Elsevier

Clinical Therapeutics

Volume 38, Issue 1, 1 January 2016, Pages 149-160
Clinical Therapeutics

Liraglutide Versus Exenatide Once Weekly: Persistence, Adherence, and Early Discontinuation

https://doi.org/10.1016/j.clinthera.2015.11.017Get rights and content

Abstract

Purpose

This study examines real-world, evidence-based comparisons of persistence and adherence to daily versus weekly glucagon-like peptide 1 (GLP-1) receptor agonists for the treatment of type 2 diabetes (T2D).

Methods

This retrospective observational study used U.S. insurance claims data to compare persistence and adherence to GLP-1 receptor agonists in patients with T2D initiating once weekly (QW) exenatide or daily liraglutide over a 6-month follow-up period. Eligible patients had ≥2 diagnoses of T2D, were 18 years of age or older, initiated a new prescription of either the index drug between February 1, 2012 (market availability launch date of exenatide QW) and March 31, 2013, and had ≥6 months continuous eligibility in the pre- and postindex periods. A 1:1 propensity score match was used to account for selection bias. Outcome measures included persistence as measured by the percentage of patients who continued to take the index drug over an index period of 182 days with an allowable gap of 60 days and adherence as measured by the proportion of days covered (PDC). The percentage of patients achieving PDC ≥0.8 and ≥0.9 was also calculated.

Findings

There were no significant differences between baseline characteristics after propensity score matching. Each matched cohort included 12,306 patients. The overall persistence observed with liraglutide was 66% compared with 63% for exenatide QW. The mean (SD) PDC adherence during the 6-month follow-up period was 0.694 (0.309) for the exenatide QW cohort and 0.689 (0.286) for the liraglutide cohort. The PDC threshold of ≥0.8 during the 6-month follow-up period was met by 6309 (51%) and 5820 (47%) patients in the exenatide QW and liraglutide cohorts, respectively. For the exenatide QW cohort, 76% of patients treated previously with BID exenatide continued treatment in the 6-month follow-up period compared with 59% who were not previously treated with exenatide BID. For the liraglutide cohort, 77% of previous exenatide BID patients continued treatment versus 63% of patients who were not previously treated with exenatide BID.

Implications

These results reveal slight differences in persistence and adherence rates in patients receiving exenatide QW versus patients receiving liraglutide daily that vary by outcome and previous incretin-based therapy used. Differences may be due to dosing device differences for exenatide QW and liraglutide, which, in the case of liraglutide, allows the opportunity for daily self-titration dosing. Implications of these findings for clinical practice are that persistence is determined by the broader context of treatment and medications being used and should be considered when prescribing GLP-1 receptor agonists.

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.

References (20)

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