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

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

Mona Mashayekhi  1 , Jessica R Wilson  2 , Scott Jafarian-Kerman  3 , Hui Nian  4 , Chang Yu  4 , Megan M Shuey  5 , James M Luther  6 , Nancy J Brown  6   7
Affiliations
Clinical Trial

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

Mona Mashayekhi et al. Diabetes Obes Metab. 2021 Jan.

Abstract

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.

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Conflict of interest statement

CONFLICTS OF INTEREST

None declared.

Figures

FIGURE 1
FIGURE 1
Relationship between GLP1R rs6923761 genotype and postprandial glucose, intact glucagon-like peptide-1 (GLP-1) and insulin after 1-week treatment with either placebo or sitagliptin. Plots show mean ± SD for A, glucose, B, decrease in glucose with sitagliptin treatment, C, insulin and D, GLP-1. Time zero marks ingestion of mixed meal. In B, time 0 subtracted average glucose from 45 to 240 minutes was calculated for GG versus GA/AA individuals during placebo and sitagliptin treatment, and subtracted to yield the average decrease in glucose with sitagliptin
See this image and copyright information in PMC

References

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