DPP-4 Inhibitors May Protect Against Hypoglycemia

Aims/hypothesis

Glucose-lowering therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with a low risk of hypoglycaemia. We hypothesise that DPP-4 inhibition prevents hypoglycaemia via increased glucagon counterregulation through the incretin hormone glucose-dependent insulinotropic polypeptide (GIP).

Methods

Using a hyperinsulinaemic–hypoglycaemic clamp that targeted 2.5 mmol/l we examined the effects of the DPP-4 inhibitor vildagliptin and GIP infusion on steady state glucose infusion rate (GIR) and glucagon counterregulation in mice. Following up on this, we performed a hyperinsulinaemic–hypoglycaemic clamp in mice carrying a genetic deletion of the GIP receptor (GIPR −/− mice) or the glucagon receptor (GCGR −/− mice).

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