Association between variants in TCF7L2 , CTRB1/2 , and GLP-1R genes and response to therapy with glucagon-like peptide-1 receptor agonists.

OBJECTIVES: The factors determining the response to treatment with glucagon-like peptide-1 receptor agonists (GLP-1- RAs) have not been clarified. The present study investigated the association between polymorphisms in TCF7L2 , CTRB1/2 , and GLP-1 R genes and response to GLP-1 RAs regarding glycemic control and weight loss among Greek patients with type 2 diabetes mellitus (T2DM).

METHODS: Patients ( n  = 191) treated with GLP-1 RAs for at least 6 months were included. Participants were genotyped for TCF7L2 rs7903146 (C>T), CTRB1/2 rs7202877 (T>G) and GLP-1 R rs367543060 (C>T) polymorphisms. Clinical and laboratory parameters were measured before, 3, and 6 months after treatment initiation. The patients were classified into responders and non-responders according to specific criteria.

RESULTS: Carriers of at least one rs7903146 'T' allele and rs7202877 'G' allele presented similar glucose control and weight loss response to GLP-1 RAs with the respective homozygous wild-type genotypes [odds ratio (OR): 1.08, 95% confidence interval (CI): 0.5, 2.31, p  = 0.85 and OR: 1.35, 95% CI: 0.66, 2.76, p  = 0.42; OR: 1.4, 95% CI: 0.56, 3.47, p  = 0.47 and OR: 1.28, 95% CI: 0.55, 2.98, p  = 0.57, respectively]. Regarding the GLP-1 R polymorphism, all participants were homozygous for the wild-type allele; thus, no comparisons were feasible. Female sex ( p  = 0.03) and lower baseline weight ( p  = 0.024) were associated with an improved glycemic and weight loss response, respectively.

CONCLUSION: There is no evidence suggesting a role for the variants studied in response to GLP-1 RA therapy in people with T2DM. However, specific demographic and clinical factors may be related to a better response to treatment with these agents.