The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes
Open accessAbstract
BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic cancer (P=0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.).
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“There are a number of other trials regarding cardiovascular outcomes in high-risk cohorts of patients with type 2 diabetes in which similar magnitude effects on glycemic control have been shown but without significant benefits with respect to rates of cardiovascular events or death.”
From Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (2016) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“have shown that DPP4i exhibit cardiovascular neutrality in T2DM patients.”
From The effect of GLP ‐1 receptor agonists on circulating inflammatory markers in type 2 diabetes patients: A systematic review and meta‐analysis (2025) · cites this paper as [136]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Evidence that glucose lowering reduces the rates of cardiovascular events and death has not been convincingly shown, 4-6”
From Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (2015) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Across the trials of this drug class, there appears to be no interaction by age-group (110-112).”
From 13. Older Adults: Standards of Care in Diabetes—2024 (2024) · cites this paper as [111]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“However, three other cardiovascular outcomes trials-Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) (293), Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) (294), and the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) (295)-did not find a significant increase in risk of heart failure hospitalization with D”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [294]
The cited source says what the claim attributes to it.
In the citing paper
“However, three other cardiovascular outcomes trials—Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) (312), Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) (313), and the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) (314)—did not find a significant increase in risk of heart failure hospitalization with D”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [313]
The cited source says what the claim attributes to it.
In the citing paper
“The comparator, sitagliptin, served as a placebo proxy regarding the outcome of interest as it showed no effect on heart failure events in a major randomized clinical trial and previously successfully served as a placebo proxy in claims data analyses.15,18,19”
From Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction (2025) · cites this paper as [19]
In the citing paper
“The observed annualized primary endpoint event rate for placebo patients in REDUCE-IT was 5.74%, which is consistent with historical cardiovascular outcome studies, including those published since the design of REDUCE-IT, with comparable patient populations and expanded or hard major adverse cardiovascular events (MACE) (4,8,9,30-44).”
From Effects of Icosapent Ethyl on Total Ischemic Events (2019) · cites this paper as [31]
In the citing paper
“Excepting glimepiride, which was assessed for CV safety and efficacy head-to-head against linagliptin in the CAROLINA trial, and gliclazidemodified release, which was compared with usual care (that could have included treatment with a sulphonylurea other than gliclazide) in the ADVANCE trial, dedicated CV safety assessments have not been conducted for the other sulphonylureas.132,173,174,184”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [174]
In the citing paper
“Sitagliptin and linagliptin had a neutral effect.174,[178][179][180]”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [174]
In the citing paper
“In 4 trials to date, the DPP4 inhibitors have been shown to be neutral in terms of cardiovascular outcomes.”
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 [215]
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 [18]
In the citing paper
“Likewise, sitagliptin in the TECOS trial had no signal of excess rates of HF. 18,185”
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 [18]
In the citing paper
“In mice, GLP-1 causes vasodilation through both GLP-1 receptor-dependent and -independent mechanisms.211”
From The Vasculature in Prediabetes (2018) · cites this paper as [211]
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Citations
Cites
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Self-citation10-year follow-up of intensive glucose control in type 2 diabetes
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Self-citationEffect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
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Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus
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
Self-citationAlogliptin after acute coronary syndrome in patients with type 2 diabetes
White, W. B., Cannon, C. P., Heller, S. R., Nissen, S. E., Bergenstal, R. M., Bakris, G. L., Perez, A. T., Fleck, P. R., Mehta, C. R., Kupfer, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305889 · Cited by 2,502
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The role of gut hormones in glucose homeostasis
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Pancreatic safety of incretin-based drugs–FDA and EMA assessment
Egan, A. G., Blind, E., Dunder, K., de Graeff, P. A., Hummer, B. T., Bourcier, T., & Rosebraugh, C. (2014) · New England Journal of Medicine · doi:10.1056/nejmp1314078 · Cited by 498
Pancreatic Safety of Incretin-Based Drugs — FDA and EMA Assessment
(2014) · New England Journal of Medicine · doi:10.1056/nejmx140026 · Cited by 372
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McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O. D., et al. (2021) · PubMed · doi:10.1093/eurheartj/ehab670 · Cited by 19,890
2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab368 · Cited by 13,344
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315
Self-citationLiraglutide 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
Self-citation2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Benetos, A., Biffi, A., Boavida, J.-M., Capodanno, D., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab484 · Cited by 6,485
Metadata
- Authors
- 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., Lachin, J. M., McGuire, D. K., Pencina, M. J., Standl, E., Stein, P. P., Suryawanshi, S., Van de Werf, F., Peterson, E. D., & Holman, R. R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Oxford (GB)
- University of Alberta (CA)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Duke University (US)
- St. Michael's Hospital (CA)
- George Washington University (US)
- The University of Texas Southwestern Medical Center (US)
- Helmholtz Munich (DE)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-07-16
- Volume
- 373
- Issue
- 3
- Pages
- 232-242
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2142830692
- Semantic Scholar
- 5f5aabad35a6c6137b19d8640d5d6cafc91815e5
- Cited by
- 2,577
- References
- 16
- Citations by year
- 2026: 68 · 2025: 121 · 2024: 120 · 2023: 139 · 2022: 170 · 2021: 210 · 2020: 289 · 2019: 267 · 2018: 343 · 2017: 343 · 2016: 378 · 2015: 120
- FWCI
- 341.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (acceptedVersion, cc-by-nc-nd)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Lithuanian University of Health Sciences (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- UNC Libraries
- Funders
- South Australian Health and Medical 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
- sitagliptin, type 2 diabetes, cardiovascular disease, DPP-4 inhibitors, major adverse cardiovascular events, heart failure hospitalization, acute pancreatitis, pancreatic cancer, HbA1c, glycemic control, non-inferiority
- MeSH terms
- Sitagliptin Phosphate, Administration, Oral, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Follow-Up Studies, Heart Diseases, Heart Failure, Glycated Hemoglobin, Hospitalization, Humans, Hypoglycemic Agents, Pyrazines, Triazoles, Kaplan-Meier Estimate
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