Table 3: Various non-glycemic actions of DPP-4 inhibitors.

Tissues/systemsEffects of DPP-4 inhibitor

Heart(i) Reduce infarct size after myocardial ischemia/reperfusion injury [21]
(ii) Decrease cardiac fibrosis in uremic cardiomyopathy model [22]
(iii) Prevent left ventricular hypertrophy caused by continuous infusion of isoproterenol [23]

Vascular systems(i) Decrease RAGE expression [24]
(ii) Vascular relaxation and increase nitric oxide release [25]
(iii) Reduce atherosclerotic lesion [26]
(iv) Attenuate soluble DPP-4-induced VSMC proliferation [27]
(v) Increase the number of circulating EPCs and plasma level of SDF-1 in type 2 diabetic patients [28]
(vi) Neuroprotective in ischemic stroke model [29]
(vii) Reduce lipid and protein oxidation [30]
(viii) Abolish the BP-lowering effects of enalapril in patients with metabolic syndrome [31]
(ix) Prothrombotic effect [32]
(x) receptor-mediated endothelial and medial hypertrophy/hyperplasia of arterioles in a specific condition [33]

Kidney(i) Decrease NaHCO3 reabsorption in renal proximal tubule by inhibiting Na+/H+ exchanger type 3 activity [34]
(ii) Inhibit glomerulosclerosis, fibrosis, and albuminuria [35]
(iii) Stimulate extracellular matrix production in mesangial cells mediated by receptor activation [36]

LiverImprove hepatic steatosis [37]

Neuro-endocrine systems(i) Increase plasma norepinephrine after meals [38]
(ii) Enhance receptor-mediated renovascular responses to Angiotensin II in kidneys from genetically-susceptible kidneys [39]

Immune systems(i) Suppress MMP-1, proliferation and some cytokine production (IL-6, IL-1 ) in histiocytic cell lines [40, 41]
(ii) Anti-inflammatory actions [42]
(iii) Attenuation of ischemia/reperfusion injury in lung transplants in association with increased levels of intrapulmonary VIP [43]
(iv) May inhibit the cytopathic effects of HIV-1 [8]

Hematopoietic system(i) Anti-platelet effect [44]
(ii) Increased recovery of hematopoiesis after bone marrow suppression
(iii) Expansion of HPCs [45, 46]

Note: presumed problematic actions that may cause adverse CV effects are in italic.