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Introduction The TROPHIES observational study enrolled patients with type 2 diabetes mellitus (T2DM) initiating their first injectable treatment with the glucagon-like peptide 1 receptor agonists (GLP-1 RAs) dulaglutide or liraglutide. This manuscript focuses on the study design, baseline characteristics of the enrolled population, and factors associated with GLP-1 RA choice. Methods TROPHIES is a prospective, observational, 24-month study conducted in France, Germany, and Italy. Inclusion criteria include adult patients with T2DM, naïve to injectable antihyperglycemic treatments, initiating dulaglutide or liraglutide per routine clinical practice. The primary outcome is the duration of treatment on dulaglutide or liraglutide without a significant treatment change. Results The analysis included 2181 patients (dulaglutide, 1130; liraglutide, 1051) (cutoff date May 15, 2019). The population was 56% male with mean [standard deviation (SD)] patient characteristics at baseline as follows: age, 59.2 (11.0) years; body mass index (BMI), 33.9 (6.6) kg/m2; T2DM duration, 8.5 (6.9) years; and glycated hemoglobin (HbA1c), 8.2 (1.3)%. Between-cohort demographic and clinical characteristics were balanced. The mean (SD) HbA1c and BMI values for French, German, and Italian patients were, respectively, 8.6 (1.4)%, 8.2 (1.4)%, 8.0 (0.8)%; 33.3 (6.1) kg/m2, 36.0 (7.2) kg/m2, and 32.6 (5.9) kg/m2. Conclusion This study analysis at baseline provides an opportunity to evaluate between-country differences in baseline HbA1c, weight, macrovascular complications, and factors driving GLP-1 RA selection for patients with T2DM in daily practice. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01076-0., Plain Language Summary Dulaglutide and liraglutide are medications that can help people with type 2 diabetes mellitus (T2DM) to control their blood sugar levels. These medications may also reduce body weight and reduce the risk of major cardiovascular disease. Given these treatment effects, it is essential to know how they are used in everyday clinical practice. Therefore, a study is being performed in three countries (France, Germany, and Italy) in people with T2DM who had a first-ever injectable therapy for T2DM with dulaglutide or liraglutide. Here, we present the study design, the patient characteristics at the start of treatment, and the factors driving the choice of one or the other medication. We analyzed data from 2181 people with T2DM. On average, it was shown that they were middle-aged and obese. On average, these people were diagnosed with T2DM 8.5 years before the start of dulaglutide or liraglutide and had high blood sugar levels when these medications were started. The patient characteristics were slightly different between the three countries. Country-specific factors driving the choice of either medication were also identified. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01076-0.

Purpose Previous research suggests that treatment process can have an influence on patient preference and health state utilities. This study examined preferences and estimated utilities for treatment processes of two daily oral treatment regimens and two weekly injectable regimens for treatment of type 2 diabetes (T2D). Methods Participants with T2D in the UK reported preferences and valued four health state vignettes in time trade-off utility interviews. The vignettes had identical descriptions of T2D but differed in treatment process: (1) daily simple oral treatment (tablets without administration requirements), (2) daily oral semaglutide (with administration requirements per product label), (3) weekly dulaglutide injection, (4) weekly semaglutide injection. Results Interviews were completed by 201 participants (52.7% male; mean age = 58.7). Preferences between treatment processes varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral semaglutide, 0.878 for dulaglutide injection, and 0.859 for semaglutide injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences between utilities (p Conclusions Results suggest that routes of administration cannot be compared using only the simplest descriptions (e.g., oral versus injectable). Dose frequency and specific details of the treatment process administration had an impact on patient preference and health state utilities. The utilities estimated in this study may be useful in cost-utility models comparing these treatments for T2D. Results also suggest that it may be helpful to consider patient preferences for treatment process when selecting medications for patients in clinical settings.

Introduction This study aimed to describe utilization patterns, persistence, resource utilization and costs in patients with type 2 diabetes mellitus initiating treatment with glucagon-like peptide 1 receptor agonists in routine clinical practice in Spain. Methods This retrospective study of medical records in the Big-Pac database identified adults starting treatment with once-weekly (QW) dulaglutide, exenatide-QW or once-daily liraglutide between 1 November 2015 and 30 June 2017. Patients were followed for up to 18 months from treatment initiation. Data on clinical characteristics of patients, treatment patterns, average daily dose and costs were obtained for the three cohorts. Persistence over the 18-month period was evaluated using Kaplan–Meier curves. All analyses were descriptive. Results A total of 1402 patients were included in this study (dulaglutide [n = 492], exenatide-QW [n = 438] or liraglutide [n = 472]); 52.8% were men, and the mean (SD) age was 62 (11) years, glycated haemoglobin (HbA1c) was 8.1% (1.2) and body mass index was 35.5 (3.2) kg/m2 at treatment initiation. Persistence at 18 months was 59.1% (95% confidence interval [CI] 54.8–63.4) for dulaglutide, 45.7% (95% CI 41.0–50.4) for exenatide-QW and 46.6% (95% CI 42.1–51.1) for liraglutide. The average (SD) dose was 1.2 (0.4) mg/week for dulaglutide, 1.9 (0.3) mg/week for exenatide-QW and 1.1 (0.3) mg/day for liraglutide. The average reduction in HbA1c levels at 1 year was − 0.68% for patients who initiated dulaglutide, − 0.54% for patients who initiated exenatide-QW and − 0.50% for patients who initiated liraglutide. The mean (SD) total annual health care costs were €4072 (1946) for dulaglutide, €4418 (2382) for exenatide-QW and €4382 (2389) for liraglutide. Conclusion Results suggest that patients who started treatment with dulaglutide had higher persistence over 18 months, presented lower HbA1c levels at 12 months and incurred lower annual total healthcare costs than patients who initiated exenatide-QW or liraglutide. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01039-5., Plain Language Summary Type 2 diabetes has a major impact on patients psychologically and socially, as well as on healthcare costs. The glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are drugs that help maintain blood sugar at healthy levels. They are often used as the first injectable drugs if oral treatments are no longer effective. This study aimed to analyse the use of GLP-1 RAs, and the costs involved, among patients with type 2 diabetes who started treatment with once-weekly dulaglutide, once-weekly exenatide or liraglutide in routine clinical practice in Spain. An electronic database of medical records was used to obtain data from 1402 patients who started treatment with these drugs and were followed for a 1.5-year period. Results of this study suggest that patients who were prescribed dulaglutide stayed on their treatment longer and could reduce their blood sugar levels more efficiently, and at a lower cost, than those who received once-weekly exenatide or liraglutide. These findings could be helpful to physicians prescribing these drugs when considering how to improve the management of type 2 diabetes. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01039-5.

Background Health economic evaluations require cost data as key inputs. Many countries do not have standardized reference costs so costs used often vary between studies, thereby reducing transparency and transferability. The present review provided a comprehensive overview of cost sources and suggested unit costs for France, Germany and Italy, to support health economic evaluations in these countries, particularly in the field of diabetes. Methods A literature review was conducted across multiple databases to identify published unit costs and cost data sources for resource items commonly used in health economic evaluations of antidiabetic therapies. The quality of unit cost reporting was assessed with regard to comprehensiveness of cost reporting and referencing as well as accessibility of cost sources from published cost-effectiveness analyses (CEA) of antidiabetic medications. Results An overview of cost sources, including tariff and fee schedules as well as published estimates, was developed for France, Germany and Italy, covering primary and specialist outpatient care, emergency care, hospital treatment, pharmacy costs and lost productivity. Based on these sources, unit cost datasets were suggested for each country. The assessment of unit cost reporting showed that only 60% and 40% of CEAs reported unit costs and referenced them for all pharmacy items, respectively. Less than 20% of CEAs obtained all pharmacy costs from publicly available sources. Conclusions This review provides a comprehensive account of available costs and cost sources in France, Germany and Italy to support health economists and increase transparency in health economic evaluations in diabetes.

Introduction Although patient-reported outcome (PRO) measures provide important information beyond clinical data, studies that assess the PROs of type 2 diabetes mellitus (T2DM) patients initiating injectable glucose-lowering medications in routine clinical practice are limited. We describe the perspectives of patients based on a diversified panel of generic and disease-specific PRO measures at the time of enrollment (baseline) in the TROPHIES study. Methods TROPHIES is a 24-month prospective observational study performed in France, Germany, and Italy in patients with T2DM who initiated their first injectable glucose-lowering medication with once-weekly dulaglutide or once-daily liraglutide. To better understand the perspectives of these patients regarding their overall health, treatment satisfaction, and quality of life and work, the patients’ responses to the following questionnaires were collected at baseline before they initiated treatment with dulaglutide or liraglutide: EQ-5D-5L (scale: 0–1), EQ-VAS (visual analog scale: 0–100), Impact of Weight on Self-Perceptions Questionnaire (IW-SP; scale: 0–100), Diabetes Treatment Satisfaction Questionnaire Status (DTSQs; scale: 0–36), and Diabetes Productivity Measure (DPM; scale: 0–100). Analyses were descriptive in nature, with higher scores reflecting better outcomes. Results Data from patients at the time of enrollment were analyzed. At baseline, patients initiating dulaglutide (N = 1130) or liraglutide (N = 1051) rated their quality of life in terms of mean EQ-5D-5L index as 0.84 and 0.83, and in terms of mean EQ-VAS as 67.5 and 67.5, respectively. The mean baseline scores in patients initiating dulaglutide or liraglutide were 59.8 and 61.3 for IW-SP, 24.6 and 25.8 for DTSQs, 78.6 and 79.5 for DPM Life Productivity, and 87.5 and 86.8 for DPM Work Productivity, respectively. Conclusion The information from this varied panel of PRO instruments collected at baseline complements clinical outcomes data. Electronic supplementary material The online version of this article (10.1007/s13300-020-00908-9) contains supplementary material, which is available to authorized users.

Introduction Patients with type 2 diabetes mellitus (T2DM) who fail to meet glycaemic control are at increased risk of diabetes complications. For patients who cannot maintain glycaemic control with oral medication, one recommended option is to add an injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) to their treatment regimen. The purpose of this study was to examine time to treatment intensification with GLP-1 RAs, including the duration of time that patients did not maintain glycaemic control with oral medication. Methods This was a medical record review conducted in the UK via a physician survey. Patients eligible to have their records reviewed were required to be ≥ 18 years of age, have a confirmed T2DM diagnosis, and have initiated GLP-1 RA treatment for T2DM in the past 6 months. All glycated haemoglobin (HbA1c) values within 5 years prior to GLP-1 RA initiation were collected. Results A total of 113 physicians contributed data for 1096 patients (mean age at the time of GLP-1 RA initiation was 54.9 years, 55.4% were male, and 71.4% were White). Median time from T2DM diagnosis to GLP-1 RA initiation was 6.1 years. Median consecutive time patients taking oral regimens were not under glycaemic control (HbA1c > 7.0%) prior to GLP-1 RA initiation was 13.5 months. Patients treated by general practitioners (GPs) had a significantly longer duration of time with insufficient glycaemic control prior to GLP-1 RA initiation compared with patients treated by diabetes specialists (median time for specialists was 11.0 months vs. 17.0 months for GPs; p = 0.038). Conclusions Results suggest that treatment intensification is often delayed despite consistently poor glycaemic control for more than 12 months, contrary to treatment guideline recommendations. Findings from this study highlight that some T2DM patients may benefit from more rapid treatment intensification, which could improve glycaemic control and reduce the risk for many short- and long-term health complications.

Introduction The glucagon-like peptide-1 receptor agonist (GLP-1 RA) class is evolving and expanding. This retrospective database study evaluated recent real-world treatment and dosing patterns of patients with type 2 diabetes (T2D) initiating GLP-1 RAs in Belgium (BE), France (FR), Germany (DE), Italy (IT), the Netherlands (NL), and Canada (CA). Methods Adult T2D patients initiating GLP-1 RA therapy (dulaglutide [DULA], exenatide twice daily [exBID], exenatide once weekly [exQW], liraglutide [LIRA], or lixisenatide [LIXI]) from 2015 to 2016 were identified using the IQVIA (IQVIA, Durham, NC, and Danbury, CT, USA) Real-World Data Adjudicated Pharmacy Claims. The therapy initiation date was termed the ‘index date.’ Eligible patients had ≥ 180 days pre-index and ≥ 360 days post-index. Persistence (until discontinuation or switch) was evaluated over the variable follow-up using Kaplan–Meier (KM) survival analysis. Average daily dose (ADD) was calculated until discontinuation or switch. Results A total of 34,649 DULA, 3616 exBID, 11,138 exQW, 48,317 LIRA, and 2,204 LIXI patients were included in the analysis (34.9–63.2% female; median age range 53–62 years; median follow-up 16–30 months). Proportion persistent at 1-year post-index was 36.8–67.2% for DULA, 5.9–44.4% for exBID, 24.7–44.2% for exQW, 22.2–57.5% for LIRA, and 15.5–40.0% for LIXI. Median time persistent (days) was 245–381 for DULA, 62–243 for exBID, 121–319 for exQW, 103–507 for LIRA, and 99–203 for LIXI. Mean ADD was 13.21–20.43 µg for exBID, 1.44–1.68 mg for LIRA, and 19.88–20.54 µg for LIXI. Mean average weekly dose (AWD) ranged from 2.03 to 2.14 mg for exQW. Mean AWD for DULA was 1.25 mg in Canada and ranged from 1.43 to 1.53 mg in the other countries. Conclusion Across six countries, persistence was highest among DULA patients and generally lowest among exBID patients. ADD/AWD for all GLP-1 RAs was in line with the recommended label. Longer-term data would be useful to obtain a better understanding of GLP-1 RA treatment patterns over time. Funding Eli Lilly and Company, Indianapolis, IN, USA. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-0615-5) contains supplementary material, which is available to authorized users.

Introduction In type 2 diabetes (T2D), persistence with injectable glucose-lowering therapy is associated with better outcomes. This study used real-world pharmacy data to report on persistence with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D in France. Methods This retrospective cohort analysis presents longitudinal data from approximately 7500 French retail pharmacies that filled GLP-1-RA prescriptions for GLP-1 RA-naïve patients with T2D (‘index therapy’: dulaglutide; once-weekly exenatide [exenatide QW]; twice-daily exenatide [exenatide BID]; liraglutide) between January 2015 and December 2016 (follow-up ≥ 12 months). The main outcome was treatment persistence (absence of discontinuation [gap following index therapy prescription ≥ 2-fold the expected duration of that prescription] or switch [new non-index glucose-lowering prescription issued ≤ 30 days before/after index therapy discontinuation]). Persistence was calculated as the median duration through Kaplan–Meier survival analysis over the variable follow-up period and as the proportion of patients persistent at 12 months. In addition to persistence outcomes (discontinuation/switch), three other treatment modifications were assessed: augmentation/intensification with a new non-index glucose-lowering therapy; off-label dose increase (daily dose > 20 μg for exenatide BID; two consecutive prescriptions with daily dose > 1.8 mg for liraglutide); and off-label dose decrease (two consecutive prescriptions with average daily dose lower than the index dose). Off-label dose changes were not assessed for dulaglutide or exenatide QW (as single-dose, prefilled pens). Results Median persistence was longest for dulaglutide (373 days) versus liraglutide (205 days), exenatide QW (184 days) and exenatide BID (93 days). Twelve months after treatment initiation, the percentage of persistent patients ranged from 51% (dulaglutide) to 21% (exenatide BID). Overall, treatment modification occurred less commonly for dulaglutide than for the other index GLP-1 RAs. Conclusion This analysis revealed marked differences in persistence among GLP-1 RAs, which was highest for dulaglutide and lowest for exenatide BID. The prospective TROPHIES study will provide additional information about persistence with dulaglutide and liraglutide, including reasons for treatment modifications. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01055-5., Plain Language Summary Patients with type 2 diabetes (T2D) who continue to take injectable glucose-lowering therapy for the duration of time recommended by their physician (i.e. those who are ‘persistent’) usually have better outcomes than those who do not. Persistence may be quantified as the “the duration of time from initiation to discontinuation of therapy”. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are glucose-lowering agents that are often used as the first injectable drug if oral treatments are no longer effective. The aim of the current study was to use data from approximately 7500 retail pharmacies to report persistence with each of four GLP-1 RAs (dulaglutide, once-weekly exenatide [exenatide QW], twice-daily exenatide [exenatide BID] or liraglutide) in GLP-1 RA-naïve patients with T2D in France. Patients (N = 15,074) initiated treatment between January 2015 and December 2016 and were followed for ≥ 12 months. The total duration of follow-up varied among patients. Among patients, persistence over the variable follow-up period was highest for dulaglutide and lowest for exenatide BID: median persistence was longer for dulaglutide (373 days) than for liraglutide (205 days), exenatide QW (184 days) or exenatide BID (93 days). Twelve months after treatment initiation, the percentage of persistent patients ranged from 51% (dulaglutide) to 21% (exenatide BID), with intermediate values for exenatide QW (35%) and liraglutide (36%). This analysis has revealed marked differences in the persistence of patients for various GLP-1 RAs, with patients on dulaglutide showing the highest persistence and those on exenatide BID the lowest. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01055-5.

Objective: Previous studies have examined health state utilities (which are preference weightings for use in cost-effectiveness analyses) associated with injectable GLP-1 receptor agonists for treatment of type 2 diabetes (T2D). An oral formulation of semaglutide (sema) has recently become available. This study estimates health state utilities representing preferences associated with routes of administration for daily oral sema and two weekly injectable GLP-1 receptor agonists. Methods: Participants with T2D in the UK valued four health state vignettes (drafted based on drug labels and device instructions for use) in time trade-off interviews to estimate preference-based utility scores. The vignettes had identical descriptions of T2D, but differed in treatment process: (1) daily simple oral treatment (tablets without specific administration requirements), (2) daily oral sema (tablet with administration requirements per product label), (3) weekly dulaglutide (dula) injection, (4) weekly sema injection. Results: Interviews were completed by 201 participants (52.7% male; mean age=58.7). Preferences among routes of administration varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral sema, 0.878 for dula injection, and 0.859 for sema injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences among the four utility scores (p Conclusions: While some participants preferred daily oral treatment, others preferred one of the weekly injections. Results suggest that patient preferences for routes of administration cannot be compared using only the simplest descriptions (e.g., “oral” vs. “injectable”). The details of treatment administration and treatment frequency have an impact on preference and should be considered. Disclosure K. Boye: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Eli Lilly and Company. K. Cutts: Employee; Self; Evidera. K. Stewart: Employee; Self; Evidera. K. Norrbacka: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L.E. García-Pérez: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L.S. Matza: Employee; Self; Evidera.

Introduction Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. Methods Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data). Patients with ≥ 6-month follow-up (defined as evidence of any prescription activity) were included. Proportions of patients who remained persistent (continued treatment until discontinuation/switch) in the first 6 months and of those who discontinued or switched to a different GLP-1 RA over the entire follow-up were recorded. For each treatment, the average daily/weekly dosage (ADD/AWD) while persistent during the available follow-up was calculated. Results We identified 7319 patients: 92 exBID, 970 exQW, 3368 DULA, 2573 LIRA and 316 LIXI. Across treatments, 89% patients were ≥ 50 years old, 54% were males, and the median follow-up duration ranged between 8.1 and 8.7 months. At 6 months, 35% exBID, 47% exQW, 62% DULA, 50% LIRA and 40% LIXI patients remained persistent. Over the entire follow-up, median persistence days varied from 73 (exBID) to > 300 days (DULA). The mean ± SD ADD/AWD was exBID: 17.7 ± 2.1 µg/day; exQW: 2.1 ± 0.1 mg/week; DULA: 1.5 ± 0.2 mg/week; LIRA: 1.5 ± 0.2 mg/day; LIXI: 21.0 ± 5.5 µg/day. Conclusions This real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs. Among the investigated treatments, patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy. Funding Eli Lilly and Co., Indianapolis, IN, USA. Electronic supplementary material The online version of this article (10.1007/s13300-018-0396-2) contains supplementary material, which is available to authorized users.

Introduction Dulaglutide is a novel onceweekly administered glucagon-like peptide 1 receptor agonist (GLP-1 RA) for the management of type 2 diabetes mellitus (T2DM). The objective of this analysis was to estimate the cost-effectiveness of dulaglutide 1.5 mg versus exenatide QW for the management of T2DM in France. Methods The QuintilesIMS CORE Diabetes Model was used to estimate the expected lifetime direct medical costs and outcomes of T2DM from the perspective of the French National Health Service. In the absence of head-to-head data, relative efficacy was derived from a network meta-analysis. Patient cohort characteristics were derived from the AWARD-2 trial. All patients were assumed to remain on treatment for 2 years before escalating to insulin therapy. Costs included treatment costs and costs associated with long-term complications of T2DM. Utilities were estimated based on a recent systematic review. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analysis (PSA) were conducted. Cost-effectiveness acceptability curves (CEACs) were generated. Results Dulaglutide 1.5 mg was associated with lower costs (lifetime costs €41,562 vs €43,021) and increased health benefits (lifetime quality-adjusted life years: QALYs 9.804 vs 9.757) versus exenatide QW for the treatment of T2DM in France. OWSA and PSA indicated that results were robust across a range of plausible input parameters. The CEAC indicated a 99.5% probability that dulaglutide would be considered cost-effective at a willingness to pay of €30,000. Conclusion Dulaglutide 1.5 mg reduced expected costs and increased expected QALYs when compared against exenatide QW for the treatment of T2DM in France. Compared with exenatide QW, dulaglutide 1.5 mg can provide additional health benefits for patients with T2DM and may result in cost savings for payers. Funding Eli Lilly. Electronic supplementary material The online version of this article (doi:10.1007/s13300-017-0321-0) contains supplementary material, which is available to authorized users.

Background Recent publications describing long-term follow-up from landmark trials and diabetes registries represent an opportunity to revisit modeling options in type 1 diabetes mellitus (T1DM). Objectives To develop a new product-independent model capable of predicting long-term clinical and cost outcomes. Methods After a systematic literature review to identify clinical trial and registry data, a model was developed (the PRIME Diabetes Model) to simulate T1DM progression and complication onset. The model runs as a patient-level simulation, making use of covariance matrices for cohort generation and risk factor progression, and simulating myocardial infarction, stroke, angina, heart failure, nephropathy, retinopathy, macular edema, neuropathy, amputation, hypoglycemia, ketoacidosis, mortality, and risk factor evolution. Several approaches novel to T1DM modeling were used, including patient characteristics and risk factor covariance, a glycated hemoglobin progression model derived from patient-level data, and model averaging approaches to evaluate complication risk. Results Validation analyses comparing modeled outcomes with published studies demonstrated that the PRIME Diabetes Model projects long-term patient outcomes consistent with those reported for a number of long-term studies. Macrovascular end points were reliably reproduced across five different populations and microvascular complication risk was accurately predicted on the basis of comparisons with landmark studies and published registry data. Conclusions The PRIME Diabetes Model is product-independent, available online, and has been developed in line with good practice guidelines. Validation has indicated that outcomes from long-term studies can be reliably reproduced. The model offers new approaches to long-standing challenges in diabetes modeling and may become a valuable tool for informing health care policy.

Objective: Dulaglutide 1.5 mg once weekly is a novel glucagon-like peptide 1 (GLP-1) receptor agonist, for the treatment of type two diabetes mellitus (T2DM). The objective was to estimate the cost-effectiveness of dulaglutide once weekly vs liraglutide 1.8 mg once daily for the treatment of T2DM in Spain in patients with a BMI ≥30 kg/m2.Methods: The IMS CORE Diabetes Model (CDM) was used to estimate costs and outcomes from the perspective of Spanish National Health System, capturing relevant direct medical costs over a lifetime time horizon. Comparative safety and efficacy data were derived from direct comparison of dulaglutide 1.5 mg vs liraglutide 1.8 mg from the AWARD-6 trial in patients with a body mass index (BMI) ≥30 kg/m2. All patients were assumed to remain on treatment for 2 years before switching treatment to basal insulin at a daily dose of 40 IU. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to explore the sensitivity of the model to p...

Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a relatively new class of injectable drugs used in the treatment of type 2 diabetes (T2D). This retrospective database study evaluated real-world treatment patterns of T2D patients initiating GLP-1 RAs in Belgium (BE), France (FR), Germany (DE), The Netherlands (NL) and Sweden (SE). Methods Adult T2D patients initiating exenatide twice daily (exBID), exenatide once weekly (exQW), liraglutide (LIRA) or lixisenatide (LIXI) during 2013 were identified using the QuintilesIMS (QuintilesIMS, Durham, NC, and Danbury, CT, USA) longitudinal retail pharmacy databases (LRx; BE/FR/DE/NL) and national health register data (SE). Therapy initiation date was termed ‘index date.’ Eligible patients had ≥180-day pre- and variable follow-up (minimum ≥360 days post-index). Baseline patient and treatment characteristics were assessed. Treatment modification and persistence were evaluated over the 1-year follow-up. Kaplan-Meier (KM) survival curves evaluated stopping of the index therapy (first of discontinuation or switch) over the available follow-up. Results A total of 4339 exBID, 1499 exQW, 20,955 LIRA and 1751 LIXI patients were included in the analysis (45.1–61.9% female; mean age range 57.1–62.9 years). Mean follow-up ranged from 17.7 to 30.7 months. Across countries/databases, the proportion experiencing a treatment modification at 1-year ranged from 84.1 to 93.8% for exBID, 53.3–73.4% for exQW and 59.5–80.5% for LIRA patients. The proportion of LIXI patients with treatment modification was 55.0% in Belgium (N = 20) and 96.9% in Germany (LIXI taken off the German market in April 2014). In KM analyses, LIRA patients had the lowest proportion stopping therapy, while exBID patients had the highest proportion stopping therapy, across databases, with the exception of LIXI patents. Conclusion Treatment patterns varied among GLP-1 RA patients, and persistence was generally highest among LIRA and lowest among exBID across countries. Longer term data would be useful, given the recent approval of several GLP-1 RA therapies. Funding: Eli Lilly and Co., Indianapolis, IN, USA. Electronic supplementary material The online version of this article (doi:10.1007/s13300-016-0224-5) contains supplementary material, which is available to authorized users.

Aim: The prevalence of Type 2 diabetes in Canada is estimated to be 7.6% and rising. Given the substantial economic burden associated with Type 2 diabetes treatment, optimizing healthcare expenditure is extremely important. In the present analysis, we evaluated the cost–effectiveness of dulaglutide 1.5 mg, a once-weekly glucagon-like peptide 1 agonist as third-line therapy relative to insulin glargine from the perspective of a Canadian healthcare payer. Methods: A patient-level cost-utility model of Type 2 diabetes was developed to capture seven microvascular and macrovascular complications and severe and nonsevere hypoglycemia. Cohort characteristics and the relative efficacy of dulaglutide 1.5 mg and insulin glargine were derived from the AWARD-2 head-to-head trial, which was identified by systematic literature review. Cost data were derived from Canadian sources and expressed in 2016 Canadian dollars (CAD), and future cost and quality-adjusted life expectancy (QALE) estimates were discounted at 1.5% per annum. One-way and probabilistic sensitivity analyses were conducted. Results: Based on the AWARD-2 trial, relative to insulin glargine, dulaglutide 1.5 mg was projected to increase QALE by 0.38 quality-adjusted life years and increase costs by CAD 19,773, resulting in an incremental cost–effectiveness ratio of CAD 52,580 per quality-adjusted life year gained. Conclusion: A computer simulation analysis showed that dulaglutide 1.5 mg would likely be cost-effective relative to insulin glargine in patients with Type 2 diabetes inadequately controlled on metformin and sulfonylurea in Canada.

Aims: Several glucagon like peptide-1 (GLP-1) receptor agonists are available as weekly injections for treatment of type 2 diabetes. These medications vary in their injection devices, and these differences could impact quality-of-life and patient preference. The purpose of this study was to examine patient preferences and estimate health state utilities associated with injection devices for two weekly GLP-1 therapies. Materials and methods: Participants with type 2 diabetes in Italy (Milan, Rome) valued three health state vignettes in time trade-off interviews. The health states had identical descriptions of type 2 diabetes, but differed in description of the treatment process: (1) oral treatment regimen, (2) oral plus weekly dulaglutide injection, and (3) oral plus weekly semaglutide injection. Results: A total of 216 participants completed interviews (57.9% male; mean age = 60.5). Almost all patients (99.5%) preferred the oral health state over either injection health state. Comparing between the two injections, 88.4% preferred the dulaglutide health state, while 11.6% preferred the semaglutide state. Mean (SD) utilities were 0.907 (0.076) for oral, 0.894 (0.085) for dulaglutide, and 0.887 (0.087) for semaglutide. The mean (SD) utility difference between the injection device health states was 0.007 (0.019). Limitations: Although the health states were designed to match the injection device instructions for use as closely as possible, vignette-based methods are inherently limited because results are based on perceptions of the health states rather than actual patient experience with the devices. Conclusions: Results provide insight into patient preferences associated with injection devices for weekly GLP-1 receptor agonists. The majority of patients preferred the dulaglutide device over the semaglutide device, and for some patients, this difference had an impact on utility valuations. Patient preferences for injection devices could be an important factor to consider when selecting treatments for type 2 diabetes.

Background and aims Type 1 diabetes is a chronic condition associated with micro- and macrovascular complications that have a notable impact on health-related quality of life, the magnitude of which can be quantified via the use of utility values. The aim of this review was to conduct a systematic literature review to identify and compare published health state utility values for adults with type 1 diabetes both, with and without diabetes-related complications. Methods Literature searches of the PubMed, EMBASE, and Cochrane Library databases were performed to identify English language studies on adults with type 1 diabetes, published from 2000 onward, reporting utility values for patients with or without diabetes-related complications or assessing the impact of changes in HbA1c or body mass index on quality of life. For inclusion, studies were required to report utilities elicited using validated methods. Results A total of 20 studies were included in the final review that included utility values elicited using the EuroQuol five dimensions questionnaire (n=9), 15D questionnaire (n=2), Quality of Well-Being scale (n=4), time trade-off (n=3), and standard gamble (n=2) methods. For patients with no complications, reported utility values ranged from 0.90 to 0.98. Complications including stroke (reported disutility range, -0.105 to -0.291), neuropathy (range, -0.055 to -0.358), and blindness (range, -0.132 to -0.208) were associated with the largest decrements in utility values. The magnitude of utility values and utility decrements was influenced by the assessment method used. Conclusion Complications lead to impaired health-related quality of life in patients with type 1 diabetes, the magnitude of which is influenced by the method used to determine utilities. There is currently a lack of utility data for certain complications of type 1 diabetes, meaning that many economic evaluations have relied on a combination of type 1 and type 2 diabetes utilities, despite differences between the conditions and populations, or type 1 diabetes-specific utilities derived from different instruments.

This retrospective database analysis complements previous research to understand treatment patterns for German patients newly-initiating or switching to subsequent GLP-1 RAs.Adult patients (≥18 years) initiating GLP-1 RA (Cohort 1 [C1]) or switching from a previous GLP-1 RA (Cohort 2 [C2]) to exenatide twice-daily (exBID), exenatide once-weekly (exQW), dulaglutide (DULA), or liraglutide (LIRA) were included in this analysis using IQVIA LRx from January 1, 2014-March 31, 2017. Patients were required to have ≥1 oral anti-hyperglycemic prescription during the 6-month pre-index period and ≥12 months follow-up. Persistence and treatment modifications were assessed within and beyond 12 months follow-up. Average daily/weekly dosage (ADD/AWD) was calculated during persistence.C1 included 13,417 patients, while C2 included 4,264 patients. Mean ± standard deviation (SD) age was similar (57.7 ± 11.1 years [C1], 58.9 ± 10.1 years [C2]). Most patients using DULA in C2 had switched from LIRA (56.6%). For C1, mean ADD for LIRA was 1.41 ± 0.10 mg, slightly higher in C2, and increased over time. ADD for exBID was 16.9 ± 1.0 mcg, slightly greater in C2. AWD was 2.00 ± 0.05 mg for exQW users and 1.42 ± 0.03 mg for DULA users in C1, similar to C2. For C1, 27.0% exBID, 35.3% exQW, 50.9% DULA, and 48.1% LIRA users remained persistent at 12 months. Patients using DULA had a higher probability of remaining persistent over time (Kaplan-Meier) for both cohorts.Patients using DULA had the highest probability of remaining persistent over time, followed by LIRA. ADD/AWD for DULA, exQW, and exBID were aligned with the recommended combination therapy dose; LIRA ADD suggests some patients use the 1.8 mg dose.

Louis S Matza,1 Kristina S Boye,2 Jessica B Jordan,1 Kirsi Norrbacka,3 Raffaella Gentilella,4 Amara R Tiebout,1 Chantelle Browne,5 Marco Orsini Federici,4 Giovanni Biricolti,4 Katie D Stewart1 1Patient-Centered Research, Evidera, Bethesda, MD, USA; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Eli Lilly and Company, Helsinki, Finland; 4Eli Lilly and Company, Florence, Italy; 5Modeling and Simulation, Evidera, London, UK Objectives: Several glucagon-like peptide-1 receptor agonists are administered as weekly injections for treatment of type 2 diabetes (T2D). These medications vary in their injection processes, and a recent study in the UK found that these differences had an impact on patient preference and health state utilities. The purpose of this study was to replicate the UK study in Italy to examine preferences of an Italian patient sample, while allowing for comparison between utilities in the UK and Italy.Materials and methods: Participants with T2D in Italy valued health states in time trade-off interviews. All health states had the same description of T2D, but differed in description of the treatment process. As in the original UK study, the first health state described an oral treatment regimen, while additional health states added a weekly injection. The injection health states differed in three injection-related attributes: requirements for reconstituting the medication, waiting during medication preparation, and needle handling.Results: Interviews were completed by 238 patients (58.8% male; mean age = 60.2 years; 118 from Milan, 120 from Rome). The oral treatment health state had a mean (SD) utility of 0.90 (0.10). The injection health states had significantly (p < 0.0001) lower utilities, which ranged from 0.87 (requirements for reconstitution, waiting, and handling) to 0.89 (weekly injection with none of these requirements). Differences in health state utility scores suggest that each administration requirement was associated with a disutility (ie, negative utility difference): -0.006 (reconstitution), -0.006 (needle handling), -0.011 (reconstitution, needle handling), and -0.022 (reconstitution, waiting, needle handling).Conclusion: Disutilities associated with the injection device characteristics were similar to those reported with the UK sample. Results suggest that injection device attributes may be important to some patients with T2D, and it may be useful for clinicians to consider these attributes when choosing medication for patients initiating these weekly treatments. Keywords: utility, type 2 diabetes, injection process, GLP-1 receptor agonist, time trade-off, weekly injection, Italy, injection device&nbsp

We sought to evaluate outcomes, costs of care, quality of life and predictors at 12 months in patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) and evaluated use of optimal secondary prevention therapy, defined as use of aspirin and clopidogrel along with ≥ 3 of the following 4 therapies at both hospital discharge and at one-year post-PCI: statins, beta-blockers, ARB/ACE-inhibitors, and exercise or diet.Data were from the prospective, observational APTOR study of 14 European countries from 2007 to 2009 (n=4184 patients).Optimal therapy was received in 43% of patients. Use of optimal therapy varied significantly by country. Diet or exercise at 1 year was more likely prescribed to the optimal cohort (34% vs 16%) as was dual antiplatelet therapy (99% vs 49%). Rates of CV event (3.1% vs 3.5%), bleeding (2.9% vs 2.8%) and mortality (0.9% vs 1.3%) at 1 year were similar between the optimal and non-optimal cohorts, respectively. Total costs were similar for both cohorts, but differences in post-discharge costs were observed (optimal: £1760 [£1682-£1844]; non-optimal: £1492 [£1434-£1554]), primarily due to post-discharge medication and resource use.In conclusion, in this contemporary, European ACS-PCI registry, optimal therapy was low (50%) overall, particularly for diet or exercise and dual antiplatelet therapy, highlighting a considerable gap between evidence-based guidelines and implementation of such treatments. Whether this gap reflects a missed opportunity to improve patient outcomes or whether it reflects appropriate deviation from guidelines by front-line clinicians requires further investigation.

The objective of this analysis was to estimate the cost-effectiveness of exenatide once weekly (EQW) for the treatment of type two diabetes mellitus (T2DM) in Spain. EQW was compared against exenatide twice daily (EBID) and insulin glargine (IG).The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with T2DM treated with EQW, EBID, and IG. Treatment effects and patient baseline characteristics were taken from the DURATION 3 and pooled DURATION 1 and 5 studies, in the comparison against IG and EBID, respectively. Unit costs and health state utility values were derived from published sources. To reflect diabetes progression, patients started on EQW or EBID, switching to insulin glargine after 3 years. The analysis was conducted from the perspective of the Spanish National Health Service over a time horizon of 35 years with costs and outcomes discounted at 3%. The base case included patients with a BMI 30 kg/m(2), which is in line with current prescription restrictions in Spain. Uncertainty was addressed through extensive one-way sensitivity analyses around key model parameters and a comprehensive probabilistic sensitivity analysis.When compared with EBID, EQW was the dominant strategy, i.e., less costly and more effective. When compared to IG, the incremental cost-effectiveness ratio was estimated at €12,084 per QALY gained. Sensitivity analysis indicated that the model projections were robust to the various scenarios tested.Primary limitations of the analysis are common to other T2DM analyses and include the extrapolation of short-term clinical data to the 35 year time horizon and uncertainty around optimum treatment durations.The analyses indicate that EQW is a cost-effective option for the treatment of T2DM patients in Spain for patients with a BMI 30 kg/m(2) considering a willingness-to-pay threshold of €30,000 per QALY gained.

Despite common European Society of Cardiology recommendations, adherence to guideline therapy varies, both temporally and geographically. We sought to examine current differences in the use of guideline-recommended therapies among 14 European countries in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).Data were obtained from the Antiplatelet Therapy Observational Registry (APTOR), a non-interventional, prospective observational cohort study enrolling patients with ACS undergoing PCI. Medication data were captured through 1 year. The large majority of patients in the APTOR registry received statins at hospital discharge (89%) and remained on statins at 1 year (87%), a finding that was consistent across countries. Likewise, beta-blocker use was similar at discharge and 1 year (83 and 81%, respectively). There was large disparity in aspirin loading dose between countries, but the discharge maintenance dose was more consistent, with most receiving ≤ 100 mg (87%). While 95% of patients were discharged on dual antiplatelet therapy, 71% remained on both treatments by 1 year, with wide variation by country in 1-year use.These data from the APTOR study provide key information on current European ACS patient care management from hospitalization through 1 year. Even with European Society of Cardiology (ESC) guidelines, variations in practice patterns exist among ACS patients treated with PCI between the 14 European countries studied, including the use of proven therapies, as well as appropriate duration and dosing of antiplatelet regimens. Efforts are needed to further explain why such variation exists and to continue to improve adherence to ESC guidelines to improve patient care.