Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial

Holman, Rury R.; Bethel, M. Angelyn; George, Jyothis T.; Sourij, Harald; Doran, Zoë; Keenan, Joanne F.; Khurmi, Nardev S.; Mentz, Robert J.; Oulhaj, Abderrahim; Buse, John B.; Chan, Juliana C.N.; Iqbal, Nayyar; Kundu, Sudeep; Maggioni, Aldo P.; Marso, Steven P.; Öhman, Peter; Pencina, Michael J.; Poulter, Neil; Porter, Lisa; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F.

doi:10.1016/j.ahj.2015.12.009

Cited by 82 publications

(71 citation statements)

References 35 publications

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“…If an appreciation and understanding of patients’ preference for treatment can be gained and a patient-centered approach is used during clinical decision-making, then adherence is likely to improve [7]. If adherence can be increased, then improvements in diabetes-related outcomes will be likely, including improvements in glycemic control, and reductions in short-term and long-term diabetes-related complications, and healthcare resource utilization [10, 12, 14, 34–37]. Medication regimens with less frequent dosing regimen are associated with greater adherence to medication [38].…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like Peptide-1 Receptor Agonist Treatment Attributes Important to Injection-Naïve Patients with Type 2 Diabetes Mellitus: A Multinational Preference Study

Qin

Chen

Flood³

et al. 2017

Diabetes Ther

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IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1RAs) differ in efficacy, side effects, dosing frequency, and device-related attributes. This study assessed the relative importance of treatment-related attributes in influencing preferences for GLP-1RAs among injection-naïve patients with type 2 diabetes mellitus (T2DM).MethodsInjection-naïve T2DM patients from five countries completed a Web-based discrete choice experiment (DCE) survey. Patients chose between hypothetical treatment profiles reflecting important and differentiating attributes of GLP-1RAs. Eight attributes were included: efficacy, side effects, device size, needle size, titration, preparation, evidence of long-term efficacy/safety, and dosing frequency. Odds ratios (ORs) and 95% confidence intervals were calculated using a conditional logit model to indicate the likelihood of choosing a treatment with a given attribute level versus a reference attribute level. The influence of individual attributes when considering full treatment profiles was examined using exenatide once weekly (QW) and liraglutide once daily (QD) as case examples.ResultsA total of 1482 patients with T2DM completed the DCE survey. Side effects, efficacy, and dosing frequency were the three most important attributes influencing preferences; needle size, device size, and required preparation were least important. Total sample analysis indicated that a profile of GLP-1RA approximating exenatide QW (single pen) was preferred over a profile approximating liraglutide QD (OR 3.36; p < 0.001), when efficacy was assumed to be equal.ConclusionThe most influential drivers of treatment preferences for a hypothetical GLP-RA profile were side effects, efficacy, and dosing frequency among injection-naïve T2DM patients. Preference elicitation can promote patient-centered care and inform new generations of T2DM treatments, which can lead to improved adherence and health outcomes.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0230-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Glucagon-like Peptide-1 Receptor Agonist Treatment Attributes Important to Injection-Naïve Patients with Type 2 Diabetes Mellitus: A Multinational Preference Study

Qin

Chen

Flood³

et al. 2017

Diabetes Ther

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“…The long-term benefit of exenatide QW on cardiovascular outcomes is being investigated in the phase 3/4, double-blind, placebo-controlled EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial 45. Recruitment has now been completed, with an estimated 14,000 adult patients with T2D with or without cardiovascular disease enrolled worldwide 46.…”

Section: Cardiovascular Outcomesmentioning

confidence: 99%

Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists

Courtney¹,

Nayar²,

Rajeswaran³

et al. 2017

DMSO

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Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy. This review summarizes the key efficacy and safety findings from prospective phase 3 clinical studies of at least 76 weeks’ duration for the GLP-1RAs currently approved in the United States and the European Union (albiglutide, dulaglutide, exenatide twice daily [BID], exenatide once weekly [QW], liraglutide, and lixisenatide). Currently, most of the long-term data are from uncontrolled extension studies, and continuous patient benefit has been observed for up to 3 years with multiple GLP-1RAs. Four-year comparative data demonstrated a longer time to treatment failure for exenatide BID than for sulfonylurea, and 3-year comparative extension data demonstrated greater glycated hemoglobin (HbA1c) reductions and weight loss with exenatide QW than with insulin glargine. Currently, the longest extension study for a GLP-1RA is the DURATION-1 study of exenatide QW, with >7 years of clinical data available. Data from DURATION-1 demonstrated that continuous HbA1c reductions and weight loss were observed for the patients continuing on the treatment, with no unexpected adverse events. Taken together, these data support GLP-1RAs as a long-term noninsulin treatment option after the failure of oral therapies.

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“…Reported recently, its results place LEADER in the same league as the DCCT (Diabetes Control and Complications Trial) (NCT00360815) and UKPDS trials [24, 25]. These studies have contributed immeasurably to modern diabetes care, and their impact cannot be understated.…”

Section: Cardiovascular Outcome Trialsmentioning

confidence: 99%

“…These studies have contributed immeasurably to modern diabetes care, and their impact cannot be understated. The results of ongoing trials such as EXSCEL (exenatide once weekly) and REWIND (dulaglutide) will also modify the way in which we view LEADER [25, 26]. The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) study (NCT01144338) will assess the impact of exenatide once weekly on major CV outcomes.…”

Section: Cardiovascular Outcome Trialsmentioning

confidence: 99%

Follow the LEADER—Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results Trial

Kalra

2016

Diabetes Ther

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This commentary analyzes the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, which has reported the cardiovascular benefits of liraglutide. It places the results of this seminal trial in the context of the evolution of diabetes care, compares them with other recently published cardiovascular outcome trials, and suggests novel mechanisms to explain the benefits and properties of liraglutide. The editorial discusses the potential impact that LEADER will have on the prevention and management of diabetes and its vascular complications.

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Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial

Cited by 82 publications

References 35 publications

Glucagon-like Peptide-1 Receptor Agonist Treatment Attributes Important to Injection-Naïve Patients with Type 2 Diabetes Mellitus: A Multinational Preference Study

Glucagon-like Peptide-1 Receptor Agonist Treatment Attributes Important to Injection-Naïve Patients with Type 2 Diabetes Mellitus: A Multinational Preference Study

Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists

Follow the LEADER—Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results Trial

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