Effects of DPP‐4 inhibitor linagliptin and GLP‐1 receptor agonist liraglutide on physiological response to hypoglycaemia in Japanese subjects with type 2 diabetes: A randomized, open‐label, 2‐arm parallel comparative, exploratory trial

Dipeptidyl peptidase‐4 (DPP‐4) inhibitors reduce the risk of hypoglycaemia, possibly through augmentation of glucose‐dependent insulinotropic polypeptide (GIP) action, but not that of glucagon‐like peptide‐1 (GLP‐1) on glucagon secretion. To examine this model in Japanese individuals with type 2 diabetes (T2D), the effects of the DPP‐4 inhibitor linagliptin on glucagon and other counter‐regulatory hormone responses to hypoglycaemia were evaluated and compared with those of the GLP‐1 receptor agonist liraglutide in a multi‐centre, randomized, open‐label, 2‐arm parallel comparative, exploratory trial. Three‐step hypoglycaemic clamp glucose tests preceded by meal tolerance tests were performed before and after 2‐week treatment with the drugs. Glucagon levels were increased during the hypoglycaemic clamp test at 2.5 mmol/L. This increase was similar in the linagliptin and liraglutide groups, both before and after the 2‐week treatment. Changes in other counter‐regulatory hormones (ie, growth hormone, cortisol, epinephrine and norepinephrine) were also similar between the groups, but were suppressed substantially after 2‐week treatment compared to baseline. In conclusion, we confirmed that the glucagon response to hypoglycaemia was not affected by linagliptin or liraglutide treatment in Japanese individuals with T2D.