The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome
Open accessAbstract
BACKGROUND: Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event. METHODS: We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina. RESULTS: The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo. CONCLUSIONS: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).
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In the citing paper
“in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial,14 the GLP-1–receptor agonist lixisenatide, which is shorter-acting than and structurally dissimilar to liraglutide, did not show any cardiovascular benefit in patients with diabetes and a recent acute coronary syndrome.”
From Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (2016) · cites this paper as [14]
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 [297]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In the CVOTs Harmony Outcomes (albiglutide vs placebo), EXSCEL (exenatide LA vs placebo), and AMPLITUDE-O (efpeglenatide vs placebo), there were numerically fewer strokes, but HRs were not significant.472,641,644”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [641]
Experimental — accuracy not yet measuredIn the citing paper
“The study showed that lixisenatide is not inferior, although not superior, to placebo in cardiovascular safety.”
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 [55]
In the citing paper
“The indication is to effectively reduce glycosylated hemoglobin levels in patients with T2DM by reducing fasting and postprandial blood glucose levels (61, 62).”
From GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach (2023) · cites this paper as [61]
In the citing paper
“In the ELIXA trial, lixisenatide 10 or 20 μg o.d. was non-inferior to placebo, but did not significantly affect a four-point MACE (three-point MACE plus hospitalization for unstable angina) in patients with T2DM post-ACS.158”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [158]
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 [158]
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 [158]
In the citing paper
“ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) was the first to report and showed that the short-acting GLP-1 receptor agonist lixisenatide had no impact on MACEs in 6068 patients after an acute coronary syndrome.”
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 [224]
In the citing paper
“The primary outcome of cardiovascular death, MI, stroke, or hospitalization for unstable angina occurred in 406 patients (13.4%) in the lixisenatide group vs. 399 (13.2%) in the placebo group (HR 1.2 [95% CI 0.89 -1.17]), which demonstrated the noninferiority of lixisenatide to placebo ( P < 0.001) but did not show superiority ( P = 0.81).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [208]
In the citing paper
“The primary outcome of cardiovascular death, MI, stroke, or hospitalization for unstable angina occurred in 406 patients (13.4%) in the lixisenatide group vs. 399 (13.2%) in the placebo group (HR 1.2 [95% CI 0.89 -1.17]), which demonstrated the noninferiority of lixisenatide to placebo ( P < 0.001) but did not show superiority ( P = 0.81).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [208]
In the citing paper
“The primary outcome of cardiovascular death, MI, stroke, or hospitalization for unstable angina occurred in 406 patients (13.4%) in the lixisenatide group vs. 399 (13.2%) in the placebo group (HR 1.2 [95% CI 0.89 -1.17]), which demonstrated the noninferiority of lixisenatide to placebo ( P < 0.001) but did not show superiority ( P = 0.81).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [208]
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 [208]
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 [279]
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 [23]
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 [23]
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Citations
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Metadata
- Authors
- Pfeffer, M. A., Claggett, B., Diaz, R., Dickstein, K., Gerstein, H. C., Køber, L. V., Lawson, F. C., Ping, L., Wei, X., Lewis, E. F., Maggioni, A. P., McMurray, J. J. V., Probstfield, J. L., Riddle, M. C., Solomon, S. D., & Tardif, J.-C.
- Affiliations
- Brigham and Women's Hospital (US)
- Stavanger University Hospital (NO)
- McMaster University (CA)
- Copenhagen University Hospital (DK)
- Sanofi (United States) (US)
- University of Zurich (CH)
- University of Washington Medical Center (US)
- Oregon Health & Science University (US)
- Montreal Heart Institute (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-12-03
- Volume
- 373
- Issue
- 23
- Pages
- 2247-2257
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2282578582
- Cited by
- 2,409
- References
- 38
- Citations by year
- 2026: 136 · 2025: 175 · 2024: 182 · 2023: 165 · 2022: 191 · 2021: 250 · 2020: 281 · 2019: 251 · 2018: 290 · 2017: 278 · 2016: 202 · 2015: 4
- FWCI
- 224.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Research Bank (Australian Catholic University) (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- 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
- lixisenatide, type 2 diabetes, acute coronary syndrome, myocardial infarction, unstable angina, GLP-1 receptor agonists, cardiovascular outcomes, non-inferiority, major adverse cardiovascular events, heart failure hospitalization, serious adverse events, hypoglycemia, pancreatitis, pancreatic neoplasms, allergic reactions
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-2 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Angina, Unstable, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Male, Middle Aged, Myocardial Infarction, Peptides, Proportional Hazards Models, Treatment Failure, Kaplan-Meier Estimate, Acute Coronary Syndrome
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