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.
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).



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.



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.



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. Trial registration NCT01617824.
Department of Medicine, University of Padova, Via Giustiniani,2, 35128, Padua, Italy. gianpaolofadini@hotmail.com.
Gian Paolo
GP
Fadini
Department of Medicine, University of Padova, Via Giustiniani,2, 35128, Padua, Italy.
Benedetta Maria
BM
Bonora
Department of Medicine, University of Padova, Via Giustiniani,2, 35128, Padua, Italy.
Mattia
M
Albiero
Department of Medicine, University of Padova, Via Giustiniani,2, 35128, Padua, Italy.
Martina
M
Zaninotto
Department of Medicine, University of Padova, Via Giustiniani,2, 35128, Padua, Italy.
Mario
M
Plebani
Department of Medicine, University of Padova, Via Giustiniani,2, 35128, Padua, Italy.
Angelo
A
Avogaro
D000368:Aged; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007118:Immunoassay; D007668:Kidney / Q000503:physiopathology; D000069476:Linagliptin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000503:physiopathology; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000069476:Linagliptin; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
Enzyme; Heart failure; Kidney disease; Linagliptin; Proteases