The effects of DPP4 inhibitors on the levels of plasma catecholamines and their metabolites in patients with type 2 diabetes

Aims: Dipeptidyl peptidase 4 inhibitors (DPP4Is) can increase sympathetic activity. We aimed to evaluate the direct association between serum DPP4 activity and sympathetic activity in humans.

Methods: Fasting serum DPP4 activity and plasma levels of catecholamines and their metabolites were measured in 211 patients with type 2 diabetes mellitus (T2DM) treated with DPP4I (n = 146) or non-DPP4I therapy (n = 65) and in healthy control subjects (n = 30).

Results: Although there were no differences in plasma levels of catecholamines and their metabolites between the DPP4I and non-DPP4I groups, the levels in both of these groups were lower than those in the healthy control group. In DPP4I-treated patients, serum DPP4 activity showed an inverse correlation with plasma levels of norepinephrine (NE) (r = -0.339, p < 0.01), metanephrine (MET) (r = -0.251, p < 0.01) and normetanephrine (r = -0.312, p < 0.001). In addition, plasma MET level showed a weak inverse correlation with serum DPP4 activity in the combined T2DM group. In DPP4I-treated patients, the inverse correlation between DPP4 activity and plasma NE remained significant even after multiple adjustments.

Conclusions: Our results suggest that although sympathetic activity is lower in patients with T2DM, the greater the suppression of DPP4 activity by DPP4I therapy, the greater the increase in sympathetic activity is, which may have clinical implications in high risk T2DM patients.