Patient Reported Outcomes following initiation of Glucagon-like peptide-1 Receptor agonists in patients with type 2 Diabetes in a specialist endocrinology practice of the LMC diabetes registry: The PROGRESS-Diabetes study

https://doi.org/10.1016/j.diabres.2019.107820Get rights and content

Abstract

Aims

To compare patient-reported outcomes and clinical outcomes in patients who initiated dulaglutide or liraglutide as part of usual clinical therapy.

Methods

This observational study enrolled adults with type 2 diabetes who initiated dulaglutide or liraglutide between April 2017 and January 2018. A prospective patient cohort completed questionnaires at baseline and at their usual follow-up visit three to six months later. Clinical outcomes were assessed in a post-hoc retrospective analysis using propensity score matching.

Results

In the per-protocol analysis, 146 dulaglutide and 79 liraglutide patients had similar significant improvements in diabetes treatment satisfaction scores (dulaglutide 9.6 ± 1.1, p < 0.001; liraglutide 10.6 ± 1.4, p < 0.001) and follow-up scores for diabetes device satisfaction. Only dulaglutide had significant improvements in medication adherence scores. In the overall cohort, 754 matched patients showed similar reductions in A1C (dulaglutide −0.8% [9 mmol/mol]; liraglutide −0.7% [8 mmol/mol]). Liraglutide patients had a greater reduction in weight than those initiating dulaglutide (−2.8 kg vs. −1.8 kg; p < 0.001).

Conclusions

Patients who initiated dulaglutide or liraglutide in a real-world specialist practice had similar improvements in diabetes medication satisfaction and diabetes device satisfaction. Only dulaglutide patients had significant improvements in medication adherence scores. Both treatment cohorts had similar patterns of A1C change, and liraglutide had significantly greater weight loss, which are similar to findings from clinical trials.

Introduction

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are injectable, non-insulin therapies for patients with T2D that improve glycemic control through several mechanisms, including stimulating glucose-dependent insulin release, slowing gastric emptying, inhibiting post-meal glucagon release and reducing appetite [1]. In addition to having proven glucose-lowering efficacy, GLP-1 RA therapies promote weight loss and are associated with a low risk for hypoglycemia, thus making them an attractive treatment option for patients with T2D [2]. GLP-1 RA therapy is recommended as a treatment option after metformin in patients with established cardiovascular disease (CVD), or for patients prioritizing weight loss or low risk of hypoglycemia. In addition, GLP-1 RA therapy is recommended prior to initiating insulin if patients are intensifying to injectable therapies [3].

Daily and weekly dosing options are available within the GLP-1 RA drug class. Dulaglutide, semaglutide and exenatide QW are administered once-weekly, liraglutide and lixisenatide are administered once-daily, and exenatide is also available for twice-daily dosing. In RCT’s comparing GLP-1 RA’s head-to-head, varying results within the class have been seen in A1C and weight reduction, as well as in gastrointestinal adverse effects [1], [3], [4].

Patient-reported outcomes (PROs), reported by participants through self-reported questionnaires, can add to RCT findings by offering a unique patient perspective on the effectiveness of a therapy. Several clinical trials of GLP-1 RA on clinical outcomes have also evaluated PRO’s. In the first head-to-head trial between GLP-1 RA, comparing once-daily liraglutide to twice-daily exenatide (LEAD 6), the liraglutide group reported significantly greater overall treatment satisfaction, and a greater reduction in perceived hypoglycemia and hyperglycemia, compared to the exenatide group [5]. In the AWARD-6 trial, both dulaglutide and liraglutide had significant improvements on impact of weight on self-perception scores and the European Quality of Life Scale, with no differences between groups [6]. In the more recent SUSTAIN-7 trial, semaglutide and dulaglutide patients had similar improvements in self-reported health status and diabetes treatment satisfaction [7].

Although RCT’s are the gold standard for determining efficacy and safety of therapeutic agents, their results may not be fully generalizable to real-world clinical practice due to their strict and limited patient inclusion criteria, as well as a bias favouring the enrollment of participants with better overall adherence. This selection bias in RCTs may be especially relevant to PRO comparisons. Evidence from studies using observational clinical data is increasingly valued and can be used to complement data from RCT’s, thus enabling clinicians to make well-informed treatment decisions for their patients [8].

To better understand the influence of once-weekly versus once-daily administration of GLP-1 RA’s on PRO’s and clinical outcomes in a real-world specialist setting, this study prospectively investigated patient and provider reported outcomes as the primary objective in patients who initiated a GLP-1 RA as part of usual therapy in a large, specialist diabetes practice in Canada. We hypothesized that patients initiating a once-weekly GLP-1 RA therapy would report greater diabetes medication satisfaction, diabetes device satisfaction, and diabetes medication adherence compared to patients initiating a once-daily GLP-1 RA therapy. Additionally, we performed a post-hoc analyses comparing clinical outcomes in a larger prospective cohort of patients initiating GLP-1 RA, using propensity score matching.

Section snippets

Subjects, materials and methods

The study used a prospective, observational design to evaluate PRO’s and clinical outcomes in patients initiating GLP-1 RA therapy during routine clinical practice. The study was conducted in compliance with the ethics principles of the Declaration of Helsinki and in compliance with all International Council on Harmonization Good Clinical Practice Guidelines. An independent ethics committee approved the protocol, and written informed consent was obtained from all study participants.

Between

Results

There were only limited numbers of patients initiating exenatide QW (n = 2), or switching GLP-1 RA’s (n = 24) and these groups were not analyzed. Albiglutide had been approved but not marketed, and semaglutide had not yet been approved in Canada. Overall, 888 GLP-1 RA naive patients initiated dulaglutide and 853 GLP-1 RA naïve patients initiated liraglutide at the six participating LMC sites between April 1, 2017 and January 30, 2018. In the prospective study portion, 318 participants were

Discussion

The present study investigated the patient experience prospectively, and clinical outcomes retrospectively, in participants with T2D initiating GLP-1 RA therapies in a large Canadian specialist practice group. Our hypothesis that participants initiating dulaglutide would have greater diabetes medication satisfaction, diabetes device satisfaction and diabetes medication adherence, was not confirmed. Dulaglutide and liraglutide cohorts had similar score gains for diabetes medication satisfaction

Acknowledgements

N/A.

Funding

A grant was provided by Eli Lilly Canada. Eli Lilly Canada was not involved in the study design, collection, analysis or interpretation of the data, writing of the report, or in the decision to submit the article for publication.

Declaration of Competing Interest

R.E.B. has no conflicts of interest to declare.

A.A reports grants and personal fees outside the submitted work from Sanofi, Novo Nordisk, Janssen, AstraZeneca, Eli Lilly, Merck, and Senseonics, personal fees from Boehringer Ingelheim and Dexcom, and grants from Amgen, Gilead, Glaxo-Smith-Kline, JDRF, Lexicon, Pfizer, Xeris, and Zealand.

H.S.B reports speaking honoraria or research support from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi and

Author contributions

All authors designed the study. R.E.B. performed the data analysis and wrote the first draft of the manuscript. All authors provided critical revisions to the manuscript and approved the final version.

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