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Ayse Dudu Altintas Dogan,1– 3 Ole Hilberg,2,3 Søren Hess,2,4 Torben Tranborg Jensen,1 Else-Marie Bladbjerg,2,5 Claus Bogh Juhl1,2,6 1Department of Medicine, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark; 2Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; 3Department of Medicine, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark; 4Department of Radiology and Nuclear Medicine, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark; 5Unit for Thrombosis Research, Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark; 6Steno Diabetes Center, Odense, DenmarkCorrespondence: Ayse Dudu Altintas Dogan, Department of Medicine, Hospital South West Jutland, University Hospital of Southern Denmark, Finsensgade 35, Esbjerg, 6700, Denmark, Tel +45 22 71 50 90, Email ayse.dudu.altintas.dogans@rsyd.dkPurpose: Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide. Obesity is commonly seen concomitantly with COPD. People with COPD have reduced quality of life, reduced physical activity, chronic respiratory symptoms, and may suffer from frequent clinical exacerbations. Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for weight loss and treatment of type-2 diabetes mellitus. In addition, liraglutide exerts anti-inflammatory actions by reducing IL-6 and MCP-1 levels. We investigated the effect of liraglutide on pulmonary function in people suffering from obesity and COPD.Patients and Methods: In this controlled, double-blind trial, 40 people with obesity and COPD from two outpatient clinics were allocated randomly to receive liraglutide (3.0 mg, s.c.) or placebo (s.c.) for 40 weeks. At baseline and after 4, 20, 40, and 44 weeks, participants underwent pulmonary-function tests, 6-min walking test, and replied to a questionnaire regarding the clinical impact of COPD (COPD assessment test (CAT)-score).Results: Compared with placebo, liraglutide use resulted in significant weight loss, increased forced vital capacity (FVC) and carbon monoxide diffusion capacity, and improved CAT-score. We found no significant changes in forced expiratory volume in one second (FEV1), FEV1/FVC, or 6-min walking distance.Conclusion: In patients suffering from obesity and COPD, 40 weeks of treatment with liraglutide improved some measures of pulmonary function. Our study suggests that liraglutide at 3.0 mg may be appropriate treatment in patients with obesity and COPD.Keywords: GLP-1 RA, COPD, obesity, inflammation, spirometry

Tracey Weiss,1 Richard D Carr,2,3 Sampriti Pal,4 Lingfeng Yang,1 Baanie Sawhney,4 Robert Boggs,1 Swapnil Rajpathak,1 Kristy Iglay1 1Center for Observational and Real-World Evidence, Merck & Co., Inc, Kenilworth, NJ, 07033, USA; 2Global Medical Affairs, Merck Sharp & Dohme Limited (MSD), Hoddesdon, EN11 9BU, UK; 3Hatter Cardiovascular Institute, University College London, London, WC1E 6HX, UK; 4Real-World Evidence, Complete HEOR Solutions (CHEORS), Pennsylvania, PA, 19454, USACorrespondence: Tracey Weiss Tel +1 (908) 873-9697Email tracey.weiss@merck.comAim: To assess adherence and discontinuation of injectable glucagon-like peptide-1 receptor agonists (GLP-1 RA) at 12 and 24 months among adult type 2 diabetes mellitus (T2DM) patients in the United States initiating GLP-1 RA using the administrative claims-based database, Optum Clinformatics® Data Mart 7.1.Methods: A retrospective study was conducted from 01/2009 to 12/2017. Patients were required to be continuously enrolled for 12 months prior to their first GLP-1 RA prescription. Proportion of days covered (PDC) from prescription claims ≥ 0.80 defined adherence. Discontinuation was defined as a ≥ 90-day gap from the last date of GLP-1 RA supply to the first date of subsequent prescription claim.Results: A total of 4791 T2DM patients had ≥ 1 and 3907 had ≥ 2 GLP-1 RA prescription claims. 50.9% and 47.4% of patients were adherent at 12 and 24 months, respectively. Adherence was significantly higher among patients on weekly vs daily doses (p< 0.001). Median time to discontinuation was 13 months. The discontinuation rate was 47.7% and 70.1% at 12 and 24 months, respectively, with differences at 24 months for age and dosing frequency (p< 0.001 for both).Conclusion: Over half of T2DM patients initiating GLP-1 RA were non-adherent and the majority (70.1%) discontinued therapy by 24 months. Reasons for non-adherence and discontinuation merit further research.Keywords: GLP-1 RA, adherence, discontinuation, United States

Vivian T Thieu,1 Susan Robinson,2 Tessa Kennedy-Martin,2 Kristina S Boye,1 Luis-Emilio Garcia-Perez1 1Global Patient Outcomes and Real-World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 2Kennedy-Martin Health Outcomes (KMHO), Brighton, UK Purpose: The importance of patient-centered care in the management of type 2 diabetes mellitus (T2DM) is widely advocated. Understanding the attributes of T2DM medications important to patients is thus essential for effective management, in order to limit disease progression. This literature review aimed to identify studies comparing patient preferences, based on process and outcome attributes, between GLP1-receptor agonist (RA) profiles and between GLP1 RA and insulin profiles. Methods: MEDLINE, Embase, PsycINFO, and the Cochrane Library (2005–present) were searched for studies in patients with T2DM or the general population that compared preferences for GLP1 RAs or GLP1 RAs versus insulin using contingent valuation, conjoint analysis (discrete-choice experiments [DCEs], willingness to pay), rating-based approaches of specific attributes, standard gamble, or time trade-off. Studies comparing drug A versus drug B without explicit attribute valuation were excluded. Results: Ten records met eligibility criteria. Eight studies compared preferences for GLP1 RA–profile attributes, one compared GLP1 RA versus insulin glargine profiles, and one addressed both comparisons. Important attributes driving patient preferences in DCEs were dose frequency, type of device, needle size, change in glycated hemoglobin, and adverse-event profile. Time trade-off evaluations demonstrated that weekly GLP1 RA injection-device attributes (reconstitution, waiting during preparation, needle handling) had a measurable impact on preference. Willingness-to-pay analysis showed that patients were more willing to pay extra for attributes of once-daily liraglutide over twice-weekly exenatide or insulin. Direct preference elicitation in DCEs revealed that patients preferred medication profiles representing GLP1 RAs with less frequent dosing and preferred GLP1 RA profiles over insulin. Conclusion: Process and outcome attributes are important drivers of patient preference for GLP1 RAs. Findings from patient-preference studies can inform clinical decision-making and help align care with patient values, which has the potential to improve medication adherence and outcomes. Keywords: T2D mellitus, discrete-choice experiment, GLP1 RA, insulin

Anne J Kugler,1 Michael L Thiman2 1Department of Pharmacy Practice and Administration, Western University of Health Sciences College of Pharmacy, Pomona, CA, USA; 2Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Athens, GA, USA Abstract: Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist, which has been on the market in the USA since 2014. Dulaglutide has performed well in head-to-head studies against metformin, glargine, and sitagliptin, where its A1c lowering ranged from -0.78% to –1.64% over 52–104 weeks, and it consistently outperformed each of these agents. As an add-on therapy, dulaglutide provided additional A1c lowering of –1.4% to –1.44% over monotherapy with glimepiride or glargine at 24 and 28 weeks, respectively. Dulaglutide outperformed exenatide when added to a regimen of metformin with pioglitazone as well as glargine when added to a regimen of metformin with glimepiride. Dulaglutide was shown to be non-inferior to liraglutide when added to metformin. In all AWARD studies other than when compared to liraglutide, dulaglutide at full strength resulted in significantly more patients achieving their A1c goal. Recent class-wide meta-analyses indicate that the incidence of commonly experienced gastrointestinal (GI) side effects is dose dependent, and nausea and vomiting are less common in longer-acting agents such as dulaglutide, but diarrhea may be more common. Pooled data have shown no increased risk of serious side effects such as pancreatitis or neoplasm with the use of dulaglutide. Given the evidence supporting liraglutide’s cardiovascular benefits, the highly anticipated REWIND trial will have a significant impact on the future place in the therapy of dulaglutide. Keywords: GLP-1 RA, glucagon-like peptide-1 receptor agonist, antidiabetic drugs, diabetes mellitus, injectable, incretin

Alan A Martin,1 Daniel Parks2 1Department of Value Evidence Analytics, GlaxoSmithKline, Uxbridge, Middlesex, UK; 2Department of Value Evidence Analytics, GlaxoSmithKline, Collegeville, PA, USA Abstract: No head-to-head comparisons exist between once-weekly (QW) glucagon-like peptide-1 receptor agonists; accordingly, this indirect comparison was conducted to evaluate the comparative efficacy of QW albiglutide vs QW exenatide. Following a systematic literature search, it was determined that HARMONY 7 and DURATION 6, Phase III trials for albiglutide and exenatide, respectively, were similar in study design and baseline characteristics and included a common comparator arm, making them suitable for an indirect comparison using the Bucher method. The primary endpoint of change from baseline in glycated hemoglobin (HbA1c) with albiglutide 50 mg QW and exenatide 2.0 mg QW was compared and tested for noninferiority. The indirect comparison showed a treatment difference of 0.0% (95% confidence interval: -0.189% to 0.189%) in mean change in HbA1c from baseline, and albiglutide 50 mg was noninferior to exenatide 2.0 mg QW at the noninferiority margin of 0.3%. In the absence of a head-to-head trial, these results can be used in pharmacoeconomic analysis and to inform health technology assessment and clinical decision making. Keywords: albiglutide, exenatide 2.0 mg QW GLP-1 RA, Bucher method

Introduction: As the prevalence of type 2 diabetes mellitus (T2DM) is anticipated to continue to rise worldwide, so too are the treatment options also continuing to expand. Current guidelines recommend individualized treatment plans which allow for provider choice and diversity of pharmacotherapeutic regimens. The glucagon-like peptide-1 receptor agonist (GLP-1 RA) class is rapidly expanding, with dulaglutide (Trulicity™) as a once-weekly agent recently approved., Aims: This article examines the evidence currently available on the efficacy and safety of dulaglutide for use in T2DM., Evidence Review: Dulaglutide has been shown to have similar efficacy and safety to other newer GLP-1 RAs, and better glycemic control than placebo. It lowers glycated hemoglobin (A1c), fasting and postprandial glucose levels, and promotes weight loss when used as first-, second-, or third-line therapy. It has also been shown to improve β-cell function and provide cardiovascular benefits, such as lower blood pressure and improved lipid levels. Dulaglutide also has a low risk for hypoglycemia and a similar adverse effect profile to other GLP-1 RAs in the class, with transient gastrointestinal problems and potential risk for pancreatitis., Place in Therapy: While long-term data on safety and efficacy are forthcoming, dulaglutide is positioned to be placed at the same level as other GLP-1 RAs in the class: as second-line therapy in addition to diet and exercise in those patients who cannot achieve glycemic control on monotherapy metformin. It may also be useful as first-line therapy instead of metformin., Conclusion: Dulaglutide is a once-weekly GLP-1 RA approved for the treatment of T2DM that has shown similar efficacy to other agents in this class.