Association of a glucagon-like peptide-1 receptor gene variant with glucose response to a mixed meal

Diabetes Obes Metab. 2021 Jan;23(1):281-286. doi: 10.1111/dom.14216. Epub 2020 Oct 22.


Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.

Keywords: DPP-4; GLP-1; GLP1R; dipeptidyl peptidase-4; glucagon-like peptide 1; sitagliptin.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / genetics
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Glucagon-Like Peptide-1 Receptor / genetics
  • Glucose
  • Humans
  • Sitagliptin Phosphate


  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Glucose
  • Sitagliptin Phosphate

Associated data