Sitagliptin decreases visceral fat and blood glucoses in women with polycystic ovarian syndrome

Context Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can increase visceral adiposity (VAT) and impair vascular function. GH releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion. Objective We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS. Methods Eighteen women with PCOS participated in a double-blinded, cross-over study. They received sitagliptin 100 mg vs. placebo daily for one month separated by an eight-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT), assessment of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm. Results During OGTT, sitagliptin increased GLP-1 (p<0.001), early insulin secretion (from mean insulinogenic index 1.9±1.2 (SD) to 3.2±3.1; p=0.02) and decreased peak glucose (mean −17.2 mg/dL [95% CI −27.7, −6.6]; p<0.01). At one month, sitagliptin decreased VAT (from 1141.9±700.7 to 1055.1±710.1 g; p=0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9±3.6 to 17.0±6.8 min, N=16; p=0.04) and interpulse interval (from 53.2±20.0 to 77.3±38.2 min, N=16; p<0.05) but did not increase mean overnight GH (p=0.92 vs. placebo). Conclusions Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval. Precis Sitagliptin improved body composition and blood glucoses following oral glucose load in women with PCOS. Sitagliptin potentiated GH half-life but did not increase overnight GH levels.