Background: Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD). Methods: B-type natriuretic peptide and NT-proBNP were measured using commercially available clinical-grade immune-assays at baseline and at the end of a 4-day treatment with placebo and linagliptin. Changes from baseline during each treatment arm, as well as placebo-subtracted effects of linagliptin on BNP and NT-proBNP were calculated. Results: 46 patients completed the study, 18 of whom were affected by CKD. Baseline BNP and NT-proBNP levels increased with age, were elevated in CKD patients, and inversely correlated with estimated glomerular filtration rate. No significant change was detected in BNP and NT-proBNP levels after treatment with linagliptin or placebo in patients with or without CKD. Only in CKD patients the placebo-subtracted effect of linagliptin indicated a significant reduction in NT-proBNP levels, but this finding was not statistically robust. Conclusions: Acute treatment with a DPP-4i exerts no clinically-meaningful effects on BNP and NT-proBNP. As routinely used immunoassays do not discriminate between intact/active and cleaved BNP, these data cannot rule out an effect of DPP-4i on HF pathophysiology.

DPP-4 inhibition has no acute effect on BNP and its N-terminal pro-hormone measured by commercial immune-assays. A randomized cross-over trial in patients with type 2 diabetes

FADINI, GIAN PAOLO;BONORA, BENEDETTA MARIA;ALBIERO, MATTIA;ZANINOTTO, MARTINA;PLEBANI, MARIO;AVOGARO, ANGELO
2017

Abstract

Background: Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD). Methods: B-type natriuretic peptide and NT-proBNP were measured using commercially available clinical-grade immune-assays at baseline and at the end of a 4-day treatment with placebo and linagliptin. Changes from baseline during each treatment arm, as well as placebo-subtracted effects of linagliptin on BNP and NT-proBNP were calculated. Results: 46 patients completed the study, 18 of whom were affected by CKD. Baseline BNP and NT-proBNP levels increased with age, were elevated in CKD patients, and inversely correlated with estimated glomerular filtration rate. No significant change was detected in BNP and NT-proBNP levels after treatment with linagliptin or placebo in patients with or without CKD. Only in CKD patients the placebo-subtracted effect of linagliptin indicated a significant reduction in NT-proBNP levels, but this finding was not statistically robust. Conclusions: Acute treatment with a DPP-4i exerts no clinically-meaningful effects on BNP and NT-proBNP. As routinely used immunoassays do not discriminate between intact/active and cleaved BNP, these data cannot rule out an effect of DPP-4i on HF pathophysiology.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/3226861
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