The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes
Open accessAbstract
BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).
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In the citing paper
“It was then found that patients with diabetes and high cardiovascular risk that were treated with liraglutide and semaglutide, but not exenatide, had a lower risk of non-fatal myocardial infarction and stroke [66, 70, 71] and another GLP-1R agonist, dulaglutide, reduced major adverse cardiovascular events [72].”
From Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes (2024) · cites this paper as [71]
The cited source says what the claim attributes to it.
In the citing paper
“However, lixisenatide and extended-release exenatide were not superior to placebo with respect to the primary end point of cardiovascular outcomes (265).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [265]
The cited source says what the claim attributes to it.
In the citing paper
“No increased risk of heart failure hospitalization has been identified in the cardiovascular outcomes trials of the GLP-1 RAs lixisenatide, liraglutide, semaglutide, exenatide once weekly, albiglutide, or dulaglutide compared with placebo (261,264,265,296,297).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [265]
The cited source says what the claim attributes to it.
In the citing paper
“Lixisenatide and extended-release exenatide were not superior to placebo with respect to the primary end point of cardiovascular outcomes (260) and therefore are not recommended for CVD risk reduction.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [260]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Risk factors include metabolic syndrome, IFG, and IGT.638–640”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [640]
Experimental — accuracy not yet measured
In the citing paper
“the results demonstrated that dulaglutide effectively and safely improves glycaemic control in diabetic patients with advanced renal disease, with impact on HbA1c fluctuations comparable to basal insulin glargine therapy.”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [59]
In the citing paper
“These findings were confirmed in all categories of patients with CKD of varying severity (baseline eGFR >60 or <60 mL/min/1.73 m2).”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [57]
In the citing paper
“dulaglutide was more effective than insulin glargine in attenuating the decline in renal function (eGFR reduction of −1.1, −1.5 and −2.9 mL/min/1.73 m2 in the three groups, respectively)”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [59]
In the citing paper
“the authors did not observe any significant correlation between the variation of creatinine (whose serum concentrations are known to depend on the patient's muscle mass) of cystatin C (which is not influenced by muscle mass) and that of body weight.”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [59]
In the citing paper
“exenatide did not produce any significant improvement in eGFR decline and incidence of ESRD and renal-related death in the EXSCEL trial”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [57]
In the citing paper
“The results showed that exenatide is noninferior to placebo in terms of safety but is not superior in terms of efficacy in preventing MACEs.”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [57]
In the citing paper
“there were no statistically significant differences on the reduction of UACR.”
From GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: state of the art (2022) · cites this paper as [59]
In the citing paper
“There were insufficient data to report a meta-analytic estimate for the frontotemporal dementia subtype (1 trial).39”
From Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis (2025) · cites this paper as [39]
In the citing paper
“In the EXSCEL trial of patients with T2DM in whom 73% had experienced a previous CV event, exenatide extended-release 2 mg once weekly showed non-inferiority but not superiority to placebo for the primary outcome of CV death, MI, and stroke.159”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [159]
In the citing paper
“Most GLP-1 RAs had a neutral effect on risk of HF hospitalization in the placebo-controlled RCTs assessing CV safety of glucose-lowering medications in patients with T2DM with or at high risk of ASCVD, despite increasing heart rate by 3-5 b.p.m. 70,72,158- 163,544”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [159]
In the citing paper
“GLP-1 RAs (lixisenatide, liraglutide, semaglutide, exenatide ER, dulaglutide, efpeglenatide) have a neutral effect on the risk of HF hospitalization, and should be considered for glucose-lowering treatment in patients with T2DM at risk of or with HF. 70,158-164,545 IIa A”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [159]
In the citing paper
“EXSCEL (Exenatide Study of Cardiovascular Event Lowering Trial; n=14 752), found extended-release exenatide to be neutral for MACEs”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [225]
In the citing paper
“However, all-cause mortality was lower in the exenatide group (HR 0.86 [95% CI 0.77 -0.97]).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [209]
In the citing paper
“The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial also reported results with the once-weekly GLP-1 receptor agonist extended-release exenatide and found that major adverse cardiovascular events were numerically lower with use of extended-release exenatide compared with placebo, although this difference was not statistically signi fi cant (209).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [209]
In the citing paper
“The incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ signi fi cantly between the two groups.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [209]
In the citing paper
“No increased risk of heart failure hospitalization has been identi fi ed in the cardiovascular outcomes trials of the GLP-1 receptor agonists lixisenatide, liraglutide, semaglutide, exenatide once-weekly, albiglutide, or dulaglutide compared with placebo ( Table 10.3 B ) (203,204,207 -209).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [209]
In the citing paper
“However, two GLP-1 analogues tested in two studies demonstrated no advantage in influencing cardiovascular outcome.278,279”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [278]
In the citing paper
“In addition, several GLP-1RAs are approved for effective glucose lowering in patients with T2DM and improve cardiovascular outcomes.20,21”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [21]
In the citing paper
“In mechanistic studies, GLP-1RAs were shown to improve cardiac function in patients with T2DM.”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [21]
In the citing paper
“Not all DPP4 inhibitors are associated with higher rates of HF (Table 8).16 -24,184-186”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [24]
In the citing paper
“In these trials, GLP-1 receptor agonists had a neutral effect on the risk for HF hospitalization.”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [24]
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Citations
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Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., & Matthews, D. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611925 · Cited by 7,830
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629
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Scirica, B. M., Bhatt, D. L., Braunwald, E., Steg, P. G., Davidson, J., Hirshberg, B., Ohman, P., Frederich, R., Wiviott, S. D., Hoffman, E. B., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1307684 · Cited by 3,470
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Green, J. B., Bethel, M. A., Armstrong, P. W., Buse, J. B., Engel, S. S., Garg, J., Josse, R., Kaufman, K. D., Koglin, J., Korn, S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501352 · Cited by 2,577
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Zoungas, S., Arima, H., Gerstein, H. C., Holman, R. R., Woodward, M., Reaven, P., Hayward, R. A., Craven, T., Coleman, R. L., & Chalmers, J. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30104-3 · Cited by 529
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Metadata
- Authors
- Holman, R. R., Bethel, M. A., Mentz, R. J., Thompson, V. P., Lokhnygina, Y., Buse, J. B., Chan, J. C., Choi, J., Gustavson, S. M., Iqbal, N., Maggioni, A. P., Marso, S. P., Öhman, P., Pagidipati, N. J., Poulter, N., Ramachandran, A., Zinman, B., & Hernandez, A. F.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-09-28
- Volume
- 377
- Issue
- 13
- Pages
- 1228-1239
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC9792409
- OpenAlex
- W2754041380
- Cited by
- 2,162
- References
- 21
- Citations by year
- 2026: 166 · 2025: 215 · 2024: 231 · 2023: 199 · 2022: 226 · 2021: 273 · 2020: 298 · 2019: 257 · 2018: 253 · 2017: 42
- FWCI
- 183.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion)
- Digital Access to Libraries (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (5t32hl069749-20)
- National Heart, Lung, and Blood Institute (T32-HL069749)
- Duke Clinical Research Institute
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- exenatide, type 2 diabetes, cardiovascular outcomes, major adverse cardiovascular events, GLP-1 receptor agonists, myocardial infarction, stroke, heart failure hospitalization, acute coronary syndrome, pancreatitis, pancreatic cancer, medullary thyroid carcinoma, non-inferiority
- MeSH terms
- Exenatide, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Administration Schedule, Female, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Male, Middle Aged, Peptides, Venoms, Incidence, Least-Squares Analysis, Kaplan-Meier Estimate
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