Purpose: Clinical response to glucagon-like peptide-1 receptor agonists (GLP1RAs) varies considerably among patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to examine the potential association between the genetic variants in GLP1R gene polymorphism with the therapeutic efficacy as well as gastrointestinal adverse drug reactions (ADRs) of GLP1RAs in Chinese T2DM patients.
Methods: Adult T2DM patients were eligible to participate in this prospective cohort study. Subjects received 12-week treatment with either exenatide (20 μg/day) or liraglutide (1.2 mg/day). GLP1R rs10305420 and rs3765467 genotyping was performed using the Sanger sequencing method. Clinical response to GLP1RAs was assessed in the patients who completed the 12-week treatment and defined by the change of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and body mass index (BMI) from the baseline.
Results: A total of 176 subjects (mean age 50.9 ± 12.7 years, 111 men) were enrolled. The planned 12-week treatment was completed by 156 patients. HbA1c reduction was significantly larger in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (1.7% ± 2.4% vs. 0.8% ± 1.8%; P = 0.002). Similarly, the 7.0% target HbA1c attainment rate was significantly higher in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (50.9% vs. 23.8%; P = 0.002). Gastrointestinal ADRs did not differ significantly among different genotypes.
Conclusion: GLP1R rs3765467 polymorphism is associated with therapeutic response to GLP1RAs in Chinese T2DM patients. HbA1c reduction is more pronounced in subjects with the GG genotype.
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