The increased dipeptidyl peptidase‐4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin‐treated patients

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Abstract
Aim: Dipeptidyl peptidase (DPP)‐4 in responsible for incretin degradation and some observations suggest that DPP‐4 activity is increased in type 2 diabetes (T2D). We aimed to assess the effect of T2D and glucose control on DPP‐4 activity. Methods: In the first set (SET1) of patients, we compared plasma DPP‐4 activity between 30 T2D and 20 age‐ and sex‐matched non‐diabetic subjects. In the second set (SET2), we measured serum DPP‐4 activity in 42 T2D patients before and after a trial of glucose control achieved by add‐on basal insulin therapy (NCT00699686). Serum/plasma DPP‐4 activity was determined using chromogenic and fluorigenic substrates, as well as several positive and negative controls. Results: In SET1, plasma DPP‐4 activity was significantly higher in T2D vs. controls (32.2 ± 1.2 U/l vs. 21.2 ± 1.1 U/l, p < 10 −6 ). From a meta‐analysis of the literature, we found that T2D is associated with a 33% increase in DPP‐4 activity compared to controls. In SET2, serum DPP‐4 activity was not lowered by intensified glucose control, despite an average haemoglobin A1c (HbA1c) reduction of 1.5%. In both sets of diabetic patients, the use of metformin was associated with a significantly lower DPP‐4 activity, independently of age, sex, body mass index and HbA1c. Conclusion: DPP‐4 activity is increased in T2D, but is not lowered by glucose control, suggesting that hyperglycaemia is not a direct determinant of DPP‐4 activity. However, metformin may indirectly reduce DPP‐4 activity.

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