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A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes.

ABSTRACT: Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes.Genetic variations of rs3765467 in GLP-1 receptor were explored in 246 patients with type 2 diabetes who received DPP-4 inhibitors treatment for 24 weeks in addition to previous medication. Patients with glycated hemoglobin (HbA1c) > 7% and who were naive to any DPP-4 inhibitors were enrolled. Responders were defined as those who showed a > 10% reduction in HbA1c after DPP-4 inhibitor treatment.DPP-4 inhibitors improved glycemic parameters and lipid profiles. Compared to the major genotype (GG), a larger proportion of patients with the minor allele genotype (GA/AA) were responders (P?=?0.018), and also showing greater HbA1c reductions (1.3?±?1.1 vs 0.9?±?1.2%; P?=?0.022). This genetic effect remained significant even after adjustment for other confounding factors (OR?=?2.00, 95% CI?=?1.03-3.89).Polymorphism in the GLP-1 receptor may influence DPP-4 inhibitor response. Further studies in larger population will help determine the association between genetic variation and interindividual differences in DPP-4 inhibitor therapy.

SUBMITTER: Han E

PROVIDER: S-EPMC5591096 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes.

Han Eugene E Park Hye Sun HS Kwon Obin O Choe Eun Yeong EY Wang Hye Jin HJ Lee Yong-Ho YH Lee Sang-Hak SH Kim Chul Hoon CH Kim Lee-Kyung LK Kwak Soo Heon SH Park Kyong Soo KS Kim Chul Sik CS Kang Eun Seok ES

Medicine 20161101 44

Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients ...[more]

PMID: 27858848

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Project description:IntroductionOral antidiabetes medications, including dipeptidyl peptidase-4 inhibitors (DPP-4is) saxagliptin and sitagliptin, are used for the treatment of type 2 diabetes (T2D). The study objective was to compare all-cause and diabetes-related costs following initiation of saxagliptin or sitagliptin.MethodsPatients aged ≥ 18 years initiating saxagliptin or sitagliptin between January 1, 2009 and January 31, 2012 in the Truven Health MarketScan Commercial and Medicare Supplemental databases were identified. Patients were required to have continuous enrollment for ≥ 365 days before and ≥ 365 days after the index date (date of the first saxagliptin or sitagliptin claim). Additionally, patients were required to have a claim with a T2D diagnosis (ICD-9-CM 250.×0, 250.×2) and no claims for a DPP-4i medication before the index date. All-cause and diabetes-related medical costs and total costs (including pharmacy costs) were captured over the 1-year follow-up period. Generalized linear models with log link and gamma distribution were fit to compare costs between the two cohorts using cost ratios, controlling for patient baseline characteristics. Recycled prediction methods were used to generate adjusted predicted costs and confidence intervals.ResultsThe final sample comprised 3354 saxagliptin initiators and 26,895 sitagliptin initiators. The average age of saxagliptin and sitagliptin initiators was 57 years and just over 50% were males. After adjusting for baseline characteristics, saxagliptin patients had significantly lower average all-cause medical costs (cost ratio = 0.901, P < 0.001; predicted mean costs: $8687 vs. $9646) compared with sitagliptin patients over the 1-year follow-up. Findings were consistent for diabetes-related medical costs (cost ratio = 0.890, P < 0.001; predicted mean costs: $2180 vs. $2450). Total costs were also lower for saxagliptin initiators (cost ratio = 0.950, P = 0.002; predicted mean costs: $13,911 vs. $14,651) over the 1-year follow-up period.ConclusionInitiation of treatment with saxagliptin was associated with lower medical costs over 1 year compared with initiation of sitagliptin among adults with T2D.FundingAstraZeneca.

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A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes.

Publications

A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes.

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