Dataset Information

Rs622342 in SLC22A1, CYP2C92 and CYP2C93 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.

ABSTRACT: BACKGROUND AND OBJECTIVE:Since the treatment outcome with oral anti-diabetics differs between individuals, the objective of this study is to evaluate the significance of rs622342 in SLC22A1, CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) with regard to the efficacy of metformin/sulfonylurea combination therapy in individuals with type 2 diabetes mellitus (T2DM). METHODS:Eighty-eight Lebanese individuals with T2DM received metformin/sulfonylurea combination therapy over 3 and 6 months. The clinical and biochemical characteristics were collected. Genotyping of rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 was performed using hybridization probes on real-time polymerase chain reaction (PCR) instrument. Statistical analysis was performed using SPSS 22.0. RESULTS:The levels of fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) showed a statistically significant reduction over 3 and 6 months of follow-up (p < 0.001). An interaction between rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 (p = 0.035) was found associated with reduced levels of HbA1c levels after 3 and 6 months. A significant difference between the means of HbA1c was observed among the different groups after 3 and 6 months (p = 0.004 and p < 0.001, respectively). The most beneficial group was; AA and AC, *1*3, whereas the individuals that benefited the least were CC, *1*3 at 3 and 6 months. In contrast to HbA1c, no interaction was found between the three polymorphisms to affect FBS (p = 0.581). CONCLUSION:The combination of metformin/sulfonylurea therapy led to the maximum glycemic control in individuals with T2DM carrying AA or AC genotypes in SLC22A1 and *1*3 in CYP2C9.

SUBMITTER: Naja K

PROVIDER: S-EPMC7354490 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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rs622342 in <i>SLC22A1</i>, <i>CYP2C9</i>2 and <i>CYP2C9</i>3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.

Naja Khaled K Salami Ali A El Shamieh Said S Fakhoury Rajaa R

Journal of personalized medicine 20200620 2

<h4>Background and objective</h4>Since the treatment outcome with oral anti-diabetics differs between individuals, the objective of this study is to evaluate the significance of rs622342 in <i>SLC22A1</i>, <i>CYP2C9</i>*2 (rs1799853) and <i>CYP2C9</i>*3 (rs1057910) with regard to the efficacy of metformin/sulfonylurea combination therapy in individuals with type 2 diabetes mellitus (T2DM).<h4>Methods</h4>Eighty-eight Lebanese individuals with T2DM received metformin/sulfonylurea combination ther ...[more]

PMID: 32575674

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Project description:BackgroundMetformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment.MethodsThis cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment.ResultsFasting plasma glucose (FPG) levels, HbA1c levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele (P < 0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (P=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (P=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA1c (r = 0.629, P < 0.001) and negatively associated with Lg10 FPG (r = -0.708, P < 0.001).ConclusionsThe variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.

Project description:IntroductionENDURE (ClinicalTrials.gov identifier, NCT00856284), a multicenter, double-blind, active-controlled study of 2639 patients with uncontrolled type 2 diabetes mellitus (T2DM), found that metformin in combination with alogliptin (12.5 and 25 mg doses), when compared to standard add-on therapy (sulfonylurea, SU), exerted sustained antihyperglycemic effects over 2 years. This economic analysis of ENDURE aimed to quantify the relationship between increased glycemic durability and cost-effectiveness of alogliptin in the UK clinical setting, and communicate its sustained glycemic benefit in economic terms.MethodsUsing baseline characteristics and treatment effects from the ENDURE trial population, between-group cost-effectiveness analyses compared the combined use of metformin and alogliptin (MET + ALO12.5/25) in patients with inadequately controlled T2DM, as an alternative to metformin and SU (MET + SU). In scenario analyses, an intragroup cost-effectiveness analysis compared MET + ALO12.5/25 with MET + SU; a between-group cost-effectiveness analysis also compared MET + ALO12.5/25 versus MET + SU within a subpopulation of patients who achieved HbA1c control (<7.5%) at 2 years on study drug.ResultsCompared with baseline profiles of patients, combination therapies with alogliptin or SU were associated with improvements in length and quality of life and were cost-effective at established norms. Despite increased drug acquisition costs, alogliptin at 12.5 mg and 25 mg doses resulted in greater predicted lifetime quality-adjusted life year (QALY) gains with associated incremental cost-effectiveness ratios (ICERs) of £10,959/QALY and £7217/QALY compared to SU, respectively.ConclusionThe ENDURE trial and the present cost-effectiveness analysis found that the glycemic durability of alogliptin therapy was associated with improved long-term patient outcomes, QALY gains, and ICERs that were cost-effective when evaluated against standard threshold values. Alogliptin therefore represents a cost-effective treatment alternative to SU as add-on therapy to metformin in patients with poorly managed T2DM.FundingTakeda Development Centre Europe Ltd.

Dataset Information

Rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.

Publications

rs622342 in <i>SLC22A1</i>, <i>CYP2C9</i>*2 and <i>CYP2C9</i>*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.

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Rs622342 in SLC22A1, CYP2C92 and CYP2C93 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.

rs622342 in <i>SLC22A1</i>, <i>CYP2C9</i>2 and <i>CYP2C9</i>3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study.