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

Diabetes, Obesity and Metabolism, 05/14/2012

Fadini GP et al. – Dipeptidyl peptidase (DPP)–4 activity is increased in type 2 diabetes (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.


  • In the first set (SET1) of patients, the authors compared plasma DPP-4 activity between 30 T2D and 20 age- and sex-matched non-diabetic subjects.
  • In the second set (SET2), they 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.


  • 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, they 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.

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