Aims Recent studies indicate that brain natriuretic peptide (BNP 1-32) may be truncated into BNP 3-32 by dipeptidyl peptidase IV (DPP4) and that BNP 3-32 has reduced biological activities compared with BNP 1-32. We investigated if DPP4 contributes to the cardiorenal alterations and to the attenuated response to BNP seen in heart failure. Methods and results Haemodynamic and renal assessment was performed in 12 pigs at baseline, 4 weeks after pacing-induced heart failure, and during BNP infusion. They were randomized to either placebo or treatment with a DPP4 inhibitor, sitagliptin. After 4 weeks of pacing, heart rate was reduced compared with baseline in the sitagliptin group (60 ± 2 vs. 95 ± 16 b.p.m. P