Exenatide Study Of Cardiovascular Event Lowering Research Articles

Identification of Subpopulations Exhibiting the Greatest Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide-1 Receptor Agonists—A Combined Analysis of Large Cardiovascular Outcome Trials

Background: By combining the results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major cardiovascular events (MACE) and identify subpopulations exhibiting the greatest cardiovascular (CV) benefit. Methods: Three multicenter, randomized, double-blind, placebo-controlled CVOTs of long-acting GLP-1 RAs were included: LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results), SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and EXSCEL (Exenatide Study of Cardiovascular Event Lowering). The primary endpoint was three-point MACE (i.e., CV death, non-fatal myocardial infarction, and non-fatal stroke). Overall effect estimates were calculated as hazard ratios (HRs) and 95% confidence intervals (CIs) using the random-effects model; pre-defined subgroup analyses were performed. Results: Overall, significant risk reductions in MACE (relative risk [RR]: 0.88 [95% CI: 0.81-0.97]) and CV death (RR: 0.85 [95% CI: 0.75-0.95]) were observed. Subgroup analysis indicated significant racial differences in this CV benefit (P for test of difference < 0.001). Risk reductions were observed in subjects of black race (RR: 0.78 [95% CI: 0.60-0.99]) and Asians (RR: 0.35 [95% CI: 0.09-1.32]). However, post-hoc analysis using Bonferroni correction revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with subjects of white race (P < 0.0001). Conclusions: Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in diabetic study populations, and racial difference in the CV benefit was observed. The existence of extra CV benefit in Asians and the underlying mechanisms should be investigated in the future. Disclosure Y. Kang: None. Y. Cho: None. J. Choi: None. C. Woo: None. W. Lee: None. J. Park: None. C. Jung: None.

EXSCEL—Once-Weekly Exenatide Reduces Medical Resource Utilization in Patients with Type 2 Diabetes Mellitus

Objectives: To evaluate the effect of exenatide 2mg once-weekly vs. placebo in addition to usual care on medical resource use among 14,572 patients with type 2 diabetes enrolled in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL), which demonstrated a statistically non-significant reduction in major adverse cardiovascular events and a nominally significant reduction in all-cause mortality with exenatide once-weekly administration. Methods: Data on medical resource use were collected from randomization to study end. 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 modeled the relative impact of exenatide vs. placebo. Results: Mean follow-up was 3.3 years in both groups. The mean number of hospitalizations 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.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). Country-level variations in resource use were significant. Conclusions: Type 2 diabetes patients treated with exenatide in addition to usual care incurred significant reductions in inpatient hospital days and outpatient visits to their diabetes care providers compared to patients treated with placebo in addition to usual care. Disclosure S.D. Reed: Research Support; Self; AstraZeneca, Merck & Co., Inc.. Y. Li: None. H.A. Dakin: Research Support; Self; AstraZeneca, Pfizer Inc.. F. Becker: None. J. Leal: None. S. Gustavson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; AstraZeneca. B. Kartman: Employee; Self; AstraZeneca. E.T. Wittbrodt: Employee; Self; AstraZeneca. R.J. Mentz: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc. N. Pagidipati: Research Support; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi, Amgen Inc., Novo Nordisk Inc., Intarcia Therapeutics, Inc. M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. A.M. Gray: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novartis AG. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca. A.F. Hernandez: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation.

Inconclusive effects of once‐weekly exenatide on cardiovascular outcomes in type 2 diabetes

Inconclusive effects of once‐weekly exenatide on cardiovascular outcomes in type 2 diabetes

Baseline characteristics of patients enrolled in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)

EXSCEL is a randomized, double-blind, placebo-controlled trial examining the effect of exenatide once-weekly (EQW) versus placebo on time to the primary composite outcome (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in patients with type 2 diabetes mellitus (DM) and a wide range of cardiovascular (CV) risk. Patients were enrolled at 688 sites in 35 countries. We describe their baseline characteristics according to prior CV event status and compare patients with those enrolled in prior glucagon-like peptide-1 receptor agonist (GLP-1RA) outcomes trials. Of a total of 14,752 participants randomized between June 2010 and September 2015, 6,788 (46.0%) patients were enrolled in Europe; 3,708 (25.1%), North America; 2,727 (18.5%), Latin America; and 1,529 (10.4%), Asia Pacific. Overall, 73% had at least one prior CV event (70% coronary artery disease, 24% peripheral arterial disease, 22% cerebrovascular disease). The median (IQR) age was 63 years (56, 69), 38% were female, median baseline HbA1c was 8.0% (7.3, 8.9) and 16% had a prior history of heart failure. Those without a prior CV event were younger with a shorter duration of diabetes and better renal function than those with at least one prior CV event. Compared with prior GLP-1RA trials, EXSCEL has a larger percentage of patients without a prior CV event and a notable percentage who were taking a dipeptidyl peptidase-4 inhibitor at baseline (15%). EXSCEL is one of the largest global GLP-1RA trials, evaluating the safety and efficacy of EQW with a broad patient population that may extend generalizability compared to prior GLP-1RA trials (ClinicalTrials.gov number, NCT01144338).

Baseline characteristics of patients enrolled in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)

Baseline characteristics of patients enrolled in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)

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

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

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

Exenatide once-weekly is an extended release formulation of exenatide, a glucagon-like peptide-1 receptor agonist, which can improve glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usual care with usual care alone on major cardiovascular outcomes. EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35 countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years. Participants will be randomized (1:1) to receive exenatide once-weekly 2 mg or matching placebo by subcutaneous injections. The trial will continue until 1,360 confirmed primary composite cardiovascular end points, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, have occurred. The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary composite cardiovascular end point. EXSCEL is powered to detect a 15% relative risk reduction in the exenatide once-weekly group, with 85% power and a 2-sided 5% alpha. The primary safety hypothesis is that exenatide once-weekly is noninferior to usual care with respect to the primary cardiovascular composite end point. Noninferiority will be concluded if the upper limit of the CI is <1.30. EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broad range of cardiovascular risk. It will also provide long-term safety information on exenatide once-weekly in people with T2DM. ClinicalTrials.gov Identifier: NCT01144338.

Anticipation Runs High for Coming Megatrials in General Cardiology

trials due to r Preventive cardiovascular medicine will get a big boost from ongoing major randomized controlled eport results during the next several years, Eric D. Peterson, MD, MPH, predicted at the annual meeting of the American College of Cardiology in San Diego. He presented an overview of eagerly anticipated clinical trials approaching completion in three of the hottest areas of research in general cardiology: new cardiovascular disease prevention agents and strategies; innovative health policy initiatives; and optimal antithrombotic regimens across the range of chronic coronary artery disease, peripheral arterial disease, patients with atrial fibrillation who’ve undergone percutaneous coronary intervention, and cerebrovascular disease. Dr. Peterson is executive director of the Duke Clinical Research Institute (DCRI), and professor of medicine at Duke University in Durham, N C.