Related Experiment Video
Updated: Dec 14, 2025
Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
Published on: May 26, 2022
Effect of Dipeptidyl Peptidase 4 Inhibitors on Cardiovascular Events in Type-2 Diabetes Patients with Renal
Maneesha Khalse1, B Ganapathy2
1Department of Medical Affairs, Lupin limited, Mumbai, Maharashtra, India.
Insights
Dipeptidyl peptidase-4 (DPP-4) inhibitors did not increase cardiovascular risks in type 2 diabetes patients, but moderate renal dysfunction showed a higher risk of heart failure hospitalization. Further research is needed for definitive conclusions.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Recent studies suggest a potential link between DPP-4 inhibitors and increased heart failure risk, possibly related to baseline estimated glomerular filtration rate (eGFR).
- Investigating the cardiovascular (CV) safety of DPP-4 inhibitors in type 2 diabetes (T2D) patients with varying degrees of renal function is crucial.
Purpose of the Study:
- To evaluate the cardiovascular safety of DPP-4 inhibitors in T2D patients.
- To determine the influence of renal function, specifically eGFR, on the CV safety profile of DPP-4 inhibitors.
Main Methods:
- A systematic literature search was conducted for randomized controlled trials (RCTs).
- Studies included T2D patients with renal impairment (eGFR ≤60 ml/min/1.73m²).
- Evaluated CV outcomes and hospitalization for heart failure (hHF) over at least 24 weeks.
Main Results:
- Analysis of four RCTs (11,789 patients) showed no increased primary composite CV endpoints with DPP-4 inhibitors, irrespective of baseline renal function.
- Hospitalization for heart failure (hHF) was non-inferior to placebo in patients with renal insufficiency (RR 1.07; 95% CI, 0.96-1.20).
- A significant increase in heart failure risk was observed in patients with moderate renal dysfunction compared to placebo (RR 1.27; 95% CI, 1.033-1.58).
Conclusions:
- DPP-4 inhibitors did not elevate overall cardiovascular event risk across different renal function levels.
- An increased risk of hHF in T2D patients with moderate renal dysfunction and high CV risk warrants careful consideration.
- Further research is necessary to fully understand the impact of declining renal function on the CV safety of DPP-4 inhibitors.
Background:
Recent studies suggested that the increased risk of heart failure by DPP-4 inhibitors may have an interconnection with patients' baseline eGFR. We decided to investigate the effect of DPP-4 inhibitors and the degree of renal function on cardiovascular (CV) safety in type 2 diabetes (T2D) patients.
Materials And Methods:
Systemic search of literature that examined the DPP-4 inhibitors and reported cardiovascular outcomes in diabetes patients with renal impairment were performed. Studies were examined for inclusion criteria: Randomized controlled trials with reduced renal function taking DPP-4 inhibitors alone or in combination with other anti-diabetes agents reporting evaluable CV events for at least 24 weeks.
Result:
Analysis of four CV outcome studies (11,789 patients with eGFR ≤60 ml/min/1.73m2) did not find any increase in primary composite endpoints with DPP-4 inhibitors in patients stratified by baseline renal function. Rate of hospitalization due to heart failure (hHF) is found to be non-inferior to placebo group in patients with renal insufficiency (RR 1.07; 95% CI, 0.96-1.20 P = 0.26). In moderate renal dysfunction, there is a significant increase in heart failure risk compared to placebo. (RR 1.27; 95% CI, 1.033 -1.5 8; P = 0.024).
Conclusion:
Treatment with DPP-4 inhibitors did not affect the risk of cardiovascular events regardless of baseline renal function, however, an increase in the risk of hHF in moderate renal function in T2D patients with high CV risk merits careful consideration. Further research would be necessitated to reach definitive conclusion to understand the effect of declining renal function on CV safety of DPP-4 inhibitors.
Related Concept Videos
01:23Dipeptidyl Peptidase 4 Inhibitors
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:22Heart Failure Drugs: Diuretics
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant