Impact of DPP-4 inhibitors on plasma levels of BNP and NT-pro-BNP in type 2 diabetes mellitus

Abstract

Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) decrease glucose levels by regulating incretin peptides in type 2 diabetes mellitus (T2DM). This study aimed to determine the modulatory effect of DPP-4i on brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in patients with T2DM. Methods PubMed, Embase and the Cochrane Library were systematically searched to identify randomized controlled trials (RCTs) evaluating the impact of DPP-4i on BNP or NT-pro-BNP. A fixed- or random-effects model was used for quantitative analysis, according to the heterogeneity. Sensitivity analysis and publication bias were performed using standard methods. Results Nine trials with 3056 patients with T2DM were included. Meta-analysis revealed that DPP-4i did not significantly modulate the BNP (0.21 pg/mL, 95% CI − 2.36–2.79) or NT-pro-BNP level (− 7.34 pg/mL, 95% CI − 24.27–9.59). DPP-4i demonstrated no stronger effect on modulating BNP (5.17 pg/mL, 95% CI − 7.48–17.82) or NT-pro-BNP (− 9.95 pg/mL, 95% CI − 44.61–24.71) than active comparators. Pooled analysis was robust and stable after sensitivity analysis. Conclusions DPP-4i exhibits no significant effect on modulating BNP or NT-pro-BNP and shows no stronger effect than traditional antidiabetic agents in T2DM.

NT-proBNP as a predictor of death and cardiovascular events in patients with type 2 diabetes

“…In an analysis of 9 trials involving 3056 patients with T2DM, dipeptidyl peptidase-4 inhibitors (DPP-4i) showed no significant effect on modulating BNP or NT-pro-BNP [ 41 ].…”

Cardiovascular protection by DPP-4 inhibitors in preclinical studies: an updated review of molecular mechanisms

“…However, in cardiac pathology, it seems that DPP4 is implicated in high levels of NPs as it was found that genetic deletion of DPP4 improved the elevated levels of ANP and BNP in rats subjected to myocardial ischemia/reperfusion (Ku et al 2011). However, a recent meta-analysis of clinical studies on diabetic patients treated with DPP4i reported no significant effect of DPP4 on NP levels (Mu et al 2022) and this finding needs further explanation. SDF-1α is a chemokine that promotes cardiac homing of endothelial progenitor cells, to stimulate angiogenesis, which consequently improves myocardial perfusion.…”

DPP4 as a Potential Candidate in Cardiovascular Disease

“…It is well known that BNP also has the effects of diuretics and natriuretic peptides, which will reduce blood volume, resulting in decrease in blood pressure. 60 Sixthly, DPP4 inhibitor has the ability to downregulate the activity of sodium/hydrogen exchanger-3 (NHE-3), a Na + /H + exchange isomer, to inhibit sodium ion reabsorption in the renal proximal tubules and increase water and sodium excretion, which also explains its beneficial antihypertensive effect. 61 , 62 Seventhly, DPP4 inhibitor interferes with the function of the RAAS system to exert antihypertensive effects as well.…”