Sitagliptin Use in Heart Failure
Sitagliptin can be used in patients with heart failure, as it has demonstrated no increased risk for heart failure hospitalization in large cardiovascular outcome trials, unlike some other DPP-4 inhibitors such as saxagliptin. 1, 2
Evidence on DPP-4 Inhibitors and Heart Failure
Different DPP-4 inhibitors have shown varying effects on heart failure outcomes in cardiovascular outcome trials 1:
- Saxagliptin showed a 27% relative increase in the risk of heart failure hospitalization in the SAVOR-TIMI 53 trial and is not recommended in patients with heart failure 1
- Alogliptin showed no significant difference in heart failure hospitalization risk in the EXAMINE trial 1
- Sitagliptin demonstrated no impact on heart failure hospitalization risk in the TECOS trial 1, 2
The 2019 AHA/HFSA scientific statement indicates that sitagliptin specifically has not been associated with increased heart failure risk, making it a safer choice among DPP-4 inhibitors for patients with heart failure 1
Clinical Considerations for Sitagliptin in Heart Failure
The TECOS trial conclusively demonstrated that sitagliptin had no impact on the risk of cardiovascular events or heart failure hospitalization compared to placebo 1, 2
Meta-analyses evaluating the risk of heart failure hospitalization with DPP-4 inhibition as a class have shown no statistically significant increase in risk compared with placebo 1
The 2020 ESC guidelines specifically state that sitagliptin has a neutral effect on the risk of heart failure and may be considered in patients with diabetes and heart failure 1
Dose adjustment may be necessary in patients with reduced renal function, but this is not specifically related to heart failure status 3
Patient Selection and Monitoring
Patients with diabetes and heart failure should be monitored regularly for signs and symptoms of worsening heart failure when starting any diabetes medication, including sitagliptin 1
In patients with end-stage renal disease on dialysis, caution may be warranted as one study suggested an increased risk of heart failure hospitalization with sitagliptin in this specific population 4
The most recent evidence from a 2020 study showed that even higher-dose sitagliptin did not increase the risk of death or hospitalization with heart failure in older adults with chronic kidney disease 3
Comparison with Other Antidiabetic Medications
SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) are preferred first-line agents for patients with diabetes and heart failure as they have been shown to reduce heart failure hospitalizations 1
Thiazolidinediones have a strong and consistent relationship with increased risk of heart failure and should be avoided in patients with heart failure 1
Metformin remains a first-line agent for diabetes that can be safely used in stable heart failure patients with adequate renal function 1
When comparing antidiabetic medications, the risk of heart failure was higher with DPP-4 inhibitors as a class than with either GLP-1 receptor agonists or SGLT-2 inhibitors, but sitagliptin specifically has shown a neutral effect 1
Conclusion
While sitagliptin is not the preferred first-line agent for patients with diabetes and heart failure (SGLT2 inhibitors are), it represents a safe option among DPP-4 inhibitors for these patients when other medications cannot be used or as part of combination therapy. Unlike saxagliptin, which is specifically not recommended in patients at risk for heart failure, sitagliptin has demonstrated cardiovascular safety in large clinical trials.