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a lower dose will almost always produce a milder effect

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Elevated hospitalisation for HF incidence remains a concern, as reported in the SAVOR-TIMI 53 trial.5557 However, in the EXAMINE and the latest CARMELINA trials, HF incidences were neutral.58,59 DPP-4 inhibitors have been reported to inhibit degradation of endogenous peptides other than GLP-1, including stromal-cell-derived factor (SDF) 1, neuropeptide Y and substance P ( Figure 2 ).60 Potentiation of these peptides results in sympathetic activation via cyclic AMP signalling and beta-receptor activation, which may contribute to HF development and cardiac fibrosis