Becker, F

Bethel, MA

Dakin, H

Gray, AM

Gustavson, SM

Hernandez, AF

Holman, RR

Kartman, B

Leal, J

Li, Y

Mentz, RJ

Pagidipati, N

Reed, SD

Wittbrodt, E

Dakin, Helen

Becker, Frauke

Leal, Jose

Gray, Alastair

Holman, Rury

Oxford University Research Archive

DCRI COMMUNICATIONS • MAY 2018Exenatide Study of Cardiovascular Event LoweringRESULTS ■ The total number of participants with data available for this ITT analysis was 14,752. ■ Median (IQR) follow-up was 3.2 (2.2–4.4) years. ■ Nearly 40% of patients were hospitalized at least once in both groups.CONTACT INFORMATIONYanhong Li, MD yanhong.li@duke.edu DISCLOSURESNone.FUNDINGThe EXSCEL trial was funded by Amylin Pharmaceuticals, Inc., a wholly owned subsidiary of AstraZeneca.BACKGROUND■■ The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) was a randomized, placebo-controlled pragmatic clinical trial designed to assess the long-term cardiovascular safety and efficacy of exenatide, a glucagon-like peptide-1 (GLP) receptor agonist, 2mg administered once weekly, in patients with type 2 diabetes with or without previous cardiovascular diseases. ■■ Patients with type 2 diabetes with a glycated hemoglobin level of 6.5 to 10.0% (48 to 96 mmol/mol) and any level of cardiovascular risk were eligible for participation in the trial.■■ The primary outcome was time to first occurrence to any component of the major adverse cardiovascular event composite outcome (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke), with 14,752 patients from 35 countries included in the intention-to-treat (ITT) analysis. ■■ EXSCEL demonstrated a numerical reduction in major adverse cardiovascular events (hazard ratio [HR]: 0.91; 95% CI: 0.83–1.00) and a nominally significant reduction in all-cause mortality (HR: 0.86; 95% CI, 0.77–0.97) with exenatide once-weekly administration. CONCLUSIONS ■ Type 2 diabetes patients treated with exenatide in addition to usual care incurred small but significant reductions in inpatient hospital days.  ■ Although outpatient care visits to their usual diabetes care provider were significantly reduced, total outpatient care visits to all providers measured were similar.OBJECTIVESTo evaluate the economic impact of exenatide 2mg once-weekly versus placebo, given in addition to usual care, on medical resource use among patients with type 2 diabetes enrolled in EXSCEL.METHODSThis economic evaluation was conducted by health economics researchers from Duke Clinical Research Institute and the University of Oxford Health Economics Research Centre according to a prespecified detailed Health Economic Analysis Plan.DATA COLLECTIONDetailed data on medical resource use during the trial, including hospitalizations, major cardiovascular and non-cardiovascular procedures, study visits, outpatient visits to usual diabetes care providers and other providers, concomitant cardiovascular and diabetic medications, and study medications were collected in the trial case report form at 1 week, 2, 6 and 12 months, and every 6 months thereafter until end of study.STATISTICAL ANALYSES ■ Descriptive statistics, including means, standard deviations, and proportions were used to summarize medical resource use and costs by treatment group. ■ Hierarchical generalized linear models were used to compare medical resource use between groups, with an offset to account for patient-level of follow-up duration. Random intercepts modeled country-specific variations in resource use and a fixed effect model was used to assess the relative impact of exenatide vs placebo. ■ Results represent relative rates of medical resource use for exenatide versus placebo.EXSCEL: Once-Weekly Exenatide Reduces Medical Resource Utilization in Patients With Type 2 Diabetes MellitusReed SD1, Li Y1, Dakin H2, Becker F2, Leal J2, Gustavson SM3, Kartman B4, Wittbrodt E3, Mentz RJ1, Pagidipati N1, Bethel MA5, Gray AM2, Holman RR5, Hernandez AF11Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA; 2Oxford Health Economic Research Centre, University of Oxford, Oxford, UK; 3AstraZeneca Research and Development, Gaithersburg, MD, USA; 4AstraZeneca, Mölndal, Sweden; 5Diabetes Trials Unit, University of Oxford, Oxford, UK ■ The mean number of hospitalizations per patient over the study duration was similar between the two groups (0.83 in the exenatide group vs 0.84 in the placebo group; p=0.31), as were annual hospitalization rates, ranging from 0.24–0.29 per person-year from Year 1 to Year 5.  ■ The mean cumulative number of inpatient days over the trial follow-up period was 0.41 days lower in the exenatide group than in the placebo group (7.05 days vs 7.46 days, respectively; relative rate ratio: 0.910; p=0.048).  ■ Patients treated with exenatide had an average of 8.88 outpatient visits to usual diabetes care providers compared to 9.14 for patients treated with placebo (p=0.048). Outpatient visits to other healthcare providers were similar at 12.19 for the exenatide group vs 11.78 for the placebo group (p=0.80).  This results in similar number of total assessed outpatient visits between the two groups over the trial follow-up period.Figure 2. Mean Cumulative Number of hospitalizations over time by treatment group.Figure 1. Mean counts of medical resources by group*All the models were specified with negative binomial error distributions and log links and with an offset variable to account for patient-level of follow-up duration. Table 1. Number of hospitalizations per patient by ITT treatment groupNumber of  hospitalizations, n (%)Exenatide  (N=7,356)Placebo  (N=7,396)0 4,522 (61.5%) 4,508 (61.0%)1 1,445 (19.6%) 1,518 (20.5%)2 656 (8.9%) 640 (8.7%)3 316 (4.3%) 298 (4.0%)4+ 417 (5.7%) 432 (5.8%)Table 2. Medical resource use throughout trialMedical resource useExenatide  (N=7,356)Placebo  (N=7,396)Relative rate/ Means ratio (95%CI) P value*All-cause hospitalizations 0.83 (1.68) 0.84 (1.62) 0.97 (0.91 to 1.03) 0.314Inpatient days 7.05 (18.24) 7.46 (19.32) 0.91 (0.83 to 1.00) 0.048Outpatient care visits— 21.07 (23.26) 20.92 (23.55) 0.99 (0.97 to 1.02) 0.656    —to usual diabetes care provider 8.88 (11.49) 9.14 (13.10) 0.97 (0.94 to 1.00) 0.048    —to other care provider(s) 12.19 (17.61) 11.78 (16.83) 1.01 (0.97 to 1.05) 0.8040.00.10.20.30.40.50.60.70.80.91.0EQW 2 mg PlaceboMean number of all-cause hospitalizations0.83 0.8402468101214EQW 2 mg PlaceboMean inpatient days7.05 7.4602468101214EQW 2 mg PlaceboOutpatient care visits to usual diabetes care provider8.88 9.1402468101214EQW 2 mg PlaceboOutpatient care visits to other care provider12.19 11.78

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EXSCEL—once-weekly exenatide reduces medical resource utilization in patients with type 2 diabetes mellitus

EXSCEL—once-weekly exenatide reduces medical resource utilization in patients with type 2 diabetes mellitus

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