As mentioned above, B-type natriuretic peptide (BNP) and substance P are both substrates of the DPP4 enzyme and may have implications on the possible association between heart failure and gliptins use, since it is already known that BNP levels increased more than 100 times in patients with heart failure and substance P is able to increase sympathetic activity during combined inhibition of angiotensin-converting enzyme and DPP4 [30, 77, 83, 84]. Here, ACE is linked to heart failure.