Acta Diabetologica

, Volume 53, Issue 3, pp 461–468 | Cite as

Association of Sitagliptin with cardiovascular outcome in diabetic patients: a nationwide cohort study

  • Tsung-Yuan Yang
  • Yung-Po Liaw
  • Jing-Yang Huang
  • Horng-Rong Chang
  • Kai-Wei Chang
  • Kwo-Chang Ueng
Original Article



Although dipeptidyl peptidase-4 (DPP-4) inhibitor improves glycemic control, the actual cardiovascular outcomes remain unclear. The objective of this cohort study was to thus evaluate the cardiovascular outcome in diabetic patients who received DPP-4 inhibitors (Sitagliptin).


A total of 104,756 new diabetic patients were identified from the Taiwan National Health Insurance Research Database during the period from March 1, 2003 to December 31, 2011. Patients who received Sitagliptin therapy were included as exposures, and up to four age- and sex-matched controls were selected by risk-set sampling. Outcomes such as major adverse cardiovascular diseases (CVD) and deaths were assessed. Logistic regression models were applied to estimate the hazard ratios and 95 % CIs between DPP-4 inhibitor use and cardiovascular outcome.


Over a mean of 14 months, the rates of total CVD per 1000 person-months were significantly lower in Sitagliptin users (3.41 vs. 5.17, p < 0.001), whereas other different CVDs (hazard ratio [HR] 0.59; 95 % confidence interval [CI] 0.48–0.72 for coronary heart disease; HR 0.75; 95 % CI 0.59–0.96 for ischemic stroke; HR 0.86; 95 % CI 0.45–1.65 for peripheral artery occlusive disease) and all-cause mortality (HR 0.56; 95 % CI 0.41–0.74]) were also fewer after adjustment for covariates.


The results showed a favorable outcome of Sitagliptin as a class on lowering CVD incidence in patients with type 2 diabetes.


Sitagliptin Diabetes Cardiovascular outcome Mortality 



This study was supported by the Department of Internal Medicine, Chung Shan Medical University Hospital (CSH-2014-A-018), Taiwan. The authors thank Chiu-Ping Shang and Ai-Lun Yu for their assistance with regard to statistical analysis and data collection.

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interest directly relevant to the contents of this article.

Ethical standard

This study was approved by the ethical committee of Chung Shan Medical University Hospital.

Human and animal rights disclosure

This article does not contain any studies with human or animal subjects performed by any of the authors.

Informed consent

Informed consent was obtained from individual participants included in the study.


  1. 1.
    American Diabetes Association (2013) Standards of medical care in diabetes—2013. Diabetes Care 36(Suppl 1):S11–S66CrossRefPubMedCentralGoogle Scholar
  2. 2.
    Duckworth W, Abraira C, Moritz T et al (2009) Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360:129–139CrossRefPubMedGoogle Scholar
  3. 3.
    Patel A, MacMahon S, Chalmers J et al (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358(24):2560–2572CrossRefPubMedGoogle Scholar
  4. 4.
    Gerstein HC, Miller ME, Genuth S et al (2011) Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 364(9):818–828CrossRefPubMedGoogle Scholar
  5. 5.
    Cheng CL, Kao YH, Lin SJ et al (2011) Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 20(3):236–242CrossRefPubMedGoogle Scholar
  6. 6.
    UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or Insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853CrossRefGoogle Scholar
  7. 7.
    Holman RR, Paul SK, Bethel A et al (2008) 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577–1589CrossRefPubMedGoogle Scholar
  8. 8.
    Guidance for industry (2008) Diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes; availability. Food Drug Adm 73(245):77724–77725Google Scholar
  9. 9.
    Engel SS, Golm GT, Shapiro D et al (2013) Cardiovascular safety of Sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis. Cardiovasc Diabetol 12:3CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Frederich R, Alexander JH, Fiedorek FT et al (2010) A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 122(3):16–27CrossRefPubMedGoogle Scholar
  11. 11.
    Williams-Herman D, Engel S, Round E et al (2010) Safety and tolerability of Sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord 10:7CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Mosenzon O, Raz I (2012) Potential cardiovascular effects of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: current evidence and ongoing trials. Eur Heart J Suppl 14(Supplement B):B22–B29CrossRefGoogle Scholar
  13. 13.
    Patil HR, Al Badarin FJ, Al Shami HA et al (2013) Comparative safety and effectiveness of Sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ 346:f2267CrossRefGoogle Scholar
  14. 14.
    Eurich DT, Simpson S, Senthilselvan A, Asche CV, Sandhu-Minhas JK, McAlister FA (2013) Comparative safety and effectiveness of Sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ 346:f2267CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Scheller NM, Mogensen UM, Andersson C et al (2014) All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor Sitagliptin compared with metformin, a retrospective cohort study on the Danish population. Diabetes Obes Metab 16(3):231–236CrossRefPubMedGoogle Scholar
  16. 16.
    Chen DY, Wang SH, Mao CT et al (2015) Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney disease and acute myocardial infarction: a nationwide cohort study. Int J Cardiol 181(15):200–206CrossRefPubMedGoogle Scholar
  17. 17.
    Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369(14):1317–1326CrossRefPubMedGoogle Scholar
  18. 18.
    White WB, Cannon CP, Heller SR et al (2013) Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 369(14):1327–1335CrossRefPubMedGoogle Scholar
  19. 19.
    Green JB, Bethel MA, Armstrong PW et al (2015) Effect of Sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. doi: 10.1056/NEJMoa1501352 PubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Tsung-Yuan Yang
    • 1
  • Yung-Po Liaw
    • 2
  • Jing-Yang Huang
    • 3
  • Horng-Rong Chang
    • 4
  • Kai-Wei Chang
    • 1
  • Kwo-Chang Ueng
    • 4
  1. 1.Institute of Medicine, Chung Shan Medical University, Department of Internal MedicineChung Shan Medical University HospitalTaichungTaiwan
  2. 2.Department of Family and Community MedicineChung Shan Medical University HospitalTaichungTaiwan
  3. 3.Department of Public Health and Institute of Public HealthChung Shan Medical UniversityTaichungTaiwan
  4. 4.School of Medicine, Chung Shan Medical University, Department of Internal MedicineChung Shan Medical University HospitalTaichungTaiwan

Personalised recommendations