Sitagliptin reduces FAP-activity and increases intact FGF21 levels in patients with newly detected glucose abnormalities

Introduction: Fibroblast growth factor 21 (FGF21), a hormone with pleiotropic metabolic effects, is inactivated by fibroblast activation protein (FAP), a member of the dipeptidyl peptidase-IV (DPP-IV) family. We investigate if sitagliptin (DPP-IV inhibitor) inhibits FAP-activity and increases intact FGF21.Methods: Patients with impaired glucose metabolism were randomized to 100 mg sitagliptin (n = 34) or placebo (n = 37) treatment for 12 weeks. Plasma samples obtained at study entry and at 12-weeks were analysed for FAPactivity, FAP, total FGF21 and intact FGF21.Results: Sitagliptin significantly inhibited FAP-activity (497 +/- 553 vs. 48 +/- 712 RFU/min, p < 0.01) and correspondingly increased intact FGF21 (253 +/- 182 vs 141 +/- 80 ng/L, p < 0.01) compared to placebo in plasma. Sitagliptin dose-dependently inhibited the FAP-activity in vitro. Intact FGF21 was higher in patients obtaining a normal glucose tolerance regardless of treatment (p = 0.03).Conclusion: A sitagliptin-induced increase of intact FGF21 may contribute to an improved metabolic effect in patients with impaired glucose metabolism.

Automated summary

This study found that sitagliptin can inhibit FAP activity and increase intact FGF21 levels, which may contribute to improved metabolic effects in patients with impaired glucose metabolism.