Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome

J Clin Endocrinol Metab. 2020 Jan 1;105(1):136-151. doi: 10.1210/clinem/dgz028.

Abstract

Context: Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired 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-blind, crossover study. They received sitagliptin either 100 mg or placebo daily for 1 month, with crossover treatments separated by an 8-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT) and assessments 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 glucagon-like peptide-1 (P < 0.001), early insulin secretion (from mean [± SD] insulinogenic index 1.9 ± 1.2 to 3.2 ± 3.1; P = 0.02), and decreased peak glucose (mean -17.2 mg/dL [95% CI, -27.7 to -6.6]; P < 0.01). At 1 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.

Clinical trial registration: This study was registered at www.clinicaltrials.gov as NCT02122380 prior to enrollment of the first participant.

Keywords: dipeptidyl peptidase-4; growth hormone; insulin like growth factor-1; polycystic ovarian syndrome; visceral adiposity.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Cross-Over Studies
  • Dipeptidyl Peptidase 4 / chemistry*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glucose Tolerance Test
  • Human Growth Hormone / metabolism
  • Humans
  • Intra-Abdominal Fat / drug effects*
  • Middle Aged
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / metabolism*
  • Polycystic Ovary Syndrome / pathology
  • Prognosis
  • Sitagliptin Phosphate / therapeutic use*
  • Young Adult

Substances

  • Biomarkers
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Human Growth Hormone
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Sitagliptin Phosphate

Associated data

  • ClinicalTrials.gov/NCT02122380