Physicians' Academy for Cardiovascular Education

Increased HF-related hospitalizations with sitagliptin in diabetic patients with established heart failure

Weir DL et al., JACC Heart Fail. 2014 - JACC Heart Fail. 2014 Jun 25


Sitagliptin Use in Patients With Diabetes and Heart Failure: A Population-Based Retrospective Cohort Study

Weir DL, McAlister FA, Senthilselvan A, et al., 
JACC Heart Fail. 2014 Jun 25. doi: 10.1016/j.jchf.2014.04.005. [Epub ahead of print]


There is considerable controversy on how to best control blood glucose in patients with diabetes and heart failure (HF), which is a frequent complication of type 2 diabetes (T2D)[1]. Metformin is currently considered first-line treatment in this patient population [2,3]. Use of alternative treatment options sulfonylureas and insulin may be limited in these patients due to undesirable side effects such as fluid retention, weight gain and hypoglycaemia [2,3]. Thiazolidinediones (TZDs) are contraindicated in case of HF due to fluid retention.
Incretin therapies such as DPP4-inhibitors have received attention for the treatment of this patient group, since they may improve cardiorenal function, in addition to having antihyperglycaemic effects [4]. However, recent safety analyses have yielded conflicting results [5-9]. This population-based, retrospective cohort study aimed to evaluate the effects of sitagliptin in patients with T2D and HF. Primary outcome of interest was a composite endpoint of all-cause hospital admission or death. 7620 diabetic patients with incident HF were included, with median follow-up of 1.4 years (12.704 years at risk).

Main results

  • The primary composite endpoint occurred in 4137 patients (54.3%).
  • Sitagliptin users showed a similar risk of all-cause hospital admission or death as compared with patients not using sitagliptin (7.1% vs. 9.2%, adjusted odds ratio: 0.84, 95%CI: 0.69-1.03).
  • Metformin users showed a lower risk of all-cause death alone or all-cause hospitalisation alone (aOR: 0.8, 95%CI: 0.71-0.85), while users of insulin (aOR: 1.16, 95%CI: 1.05-1.28) or sulfonylureas (aOR: 1.10, 95%CI: 1.00-1.23) had a higher risk.
  • Sitagliptin use was not associated with an increased risk of HF-related hospital admission or death (9.0% vs. 9.1%, aOR: 1.34, 95%CI: 0.93-1.92). However, sitagliptin use was associated with an increased risk of HF-related hospital admission alone (aOR: 1.84, 95%CI: 1.16-2.92).


This population-based study shows that although sitagliptin is not associated with an increased risk of all-cause death or hospital admission in patients with T2D and HF, use of sitagliptin was associated with an increase in HF-related hospital admissions. The increase in HF events (yielding a number needed to harm of 29), thus may have implications for the choice of add-on therapy for patients with established HF and poorly controlled diabetes with other agents. Other studies should confirm these observations. Benefits and potential risks of sitagliptin should be carefully weighed in this patient group.  

Editorial comment [10]

The present findings are important and do add to a small but growing body of evidence that suggests DPP-4 inhibitors as a class of drugs, and possibly diabetes drugs in general, may increase the risk of heart failure. This increase in absolute risk, if present at all, appears to be small. Thus far, this association does not seem to increase significantly the risk of mortality given the neutral effects on mortality seen in the present analysis and the randomized clinical trials. The findings of this analysis, as well as other recent studies, highlight the need for well-designed trials that rigorously assess for heart failure in patients with diabetes. In the meantime, diabetic patients at risk for heart failure hospitalization (e.g., those with pre-existing heart failure) who are started on DPP-4 inhibitors, and perhaps diabetes medications in general, should be followed closely as outpatients for symptoms and signs of heart failure.”
Find this article on Pubmed


1. Eurich DT, McAlister FA, Blackburn DF, et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review. BMJ 2007;335:497.
2. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008;32 Suppl 1:S1–201.
3. Summary of revisions for the 2013 clinical practice recommendations. Diabetes Care 2013; 36 Suppl 1:S3.
4. Gomez N, Touihri K, Matheeussen V, et al. Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing-induced heart failure. Eur J Heart Fail 2012;14:14–21.
5. Patil HR, Al Badarin FJ, Al Shami HA, et al. Meta-analysis of effect of dipeptidyl peptidase-4 inhibitors on cardiovascular risk in type 2 diabetes mellitus. Am J Cardiol 2012;110:826–33.
6. Engel SS, Golm GT, Shapiro D, et al. Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis. Cardiovasc Diabetol 2013;12:3.
7. Monami M, Dicembrini I, Nardini C, et al. Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk: a metaanalysis of randomised clinical trials. Diabetes Obes Metab 2014;16:38–47.
8. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369:1317–26.
9. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369:1327–35.
10. Bhatt DL, Cavender MA. Do Dipeptidyl Peptidase-4 Inhibitors Increase the Risk of Heart Failure? JACC. Heart Failure. 2014. Doi: 10.1016 /j.jchf.2014.05.005