Effect of Dipeptidyl Peptidase 4 Inhibitors on Cardiovascular Events in Type-2 Diabetes Patients with Renal Impairment: A Systematic Review and Meta-analysis

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/1.73m(2)) 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.