scholarly journals The Impacts ofSLC22A1rs594709 andSLC47A1rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Di Xiao ◽  
Yu Guo ◽  
Xi Li ◽  
Ji-Ye Yin ◽  
Wei Zheng ◽  
...  

Background. We aimed to investigate the distributive characteristics ofSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients.Methods. The distributions ofSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy.Results. No significant difference was found between T2DM patients and healthy subjects inSLC22A1rs594709 andSLC47A1rs2289669 allele frequencies and genotype frequencies. After metformin treatment,SLC22A1rs594709 GG genotype patients showed a higher increase in FINS (p=0.015) and decrease in HOMA-IS (p=0.001) and QUICKI (p=0.002) than A allele carriers.SLC47A1rs2289669 GG genotype patients had a higher decrease in TChol (p=0.030) and LDL-C (p=0.049) than A allele carriers. AmongSLC22A1rs594709 AA genotype, patients withSLC47A1rs2289669 AA genotype showed a higher decrease in FBG (p=0.015), PINS (p=0.041), and HOMA-IR (p=0.014) than G allele carriers. However, amongSLC22A1rs594709 G allele carriers,SLC47A1rs2289669 AA genotype patients showed a higher decrease in TChol (p=0.013) than G allele carriers.Conclusion. Our data suggest thatSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients.

2019 ◽  
Author(s):  
jinfang song ◽  
Mingzhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
Yi-Qing Zhao

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 newly diagnosed T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Result: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). A total of 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a less reduction in fasting plasma glucose (FPG) levels with a less increase in homeostasis model assessment for β cell HOMA-β in the carriers of G allele at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.


2020 ◽  
Vol 30 (Suppl 1) ◽  
pp. 211-216
Author(s):  
Yuri Clement ◽  
Shamjeet Singh ◽  
Shastri Motilal ◽  
Rohan Maharaj ◽  
Marcella Nunez-Smith

Background: Metformin is the drug of first choice in people newly diagnosed with type 2 diabetes. Most patients respond to metformin monotherapy, but many others remain uncontrolled even at maximal doses. Although non-adherence is a major con­tributor to non-response, genetic polymor­phisms of organic cation transporters play an important role in clinical response. We hypothesize that genetic variants are partly responsible for non-response.Objective: This study aims to determine the allele and genotype frequencies of three single nucleotide polymorphisms (SNPs; ATM rs11212617, SLC22A1 rs594709 and SLC47A1 rs2289669) most commonly asso­ciated with failure to respond to metformin.Setting: Ten primary health care facilities in the North Central Regional Health Authority region of Trinidad.Patients: The study population will include 216 patients with diabetes adherent to metformin monotherapy for at least three months.Methods: Following a 12-hour overnight fast, blood samples will be taken to measure fasting insulin and HbA1c. DNA would be isolated and PCR will be used to determine the allele and genotype frequencies of these three SNPs in adherent diabetic patients. DNA samples will be stored for future se­quencing of these three genes to determine whether other, possibly novel, mutations are associated with poor metformin response in Trinidad.Clinical Significance: This study will high­light the prevalence of these polymorphisms in our population. Should an association be found between the polymorphisms tested and glycemic control in adherent patients on metformin monotherapy, this will have implications for further research on medica­tion initiation in newly diagnosed patients with diabetes in Trinidad.Ethn Dis. 2020; 30(Suppl 1):211-216; doi:10.18865/ed.30.S1.211


2019 ◽  
Author(s):  
Jinfang Song ◽  
Mingzhu Zhang ◽  
Jiang Ni ◽  
Tao Wang ◽  
Yi-Qing Zhao

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Results: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a reduction in fasting plasma glucose (FPG) levels with an increase in homeostasis model assessment for β cell HOMA-β in the carriers of genotype CG + GG at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers. Trial registration: This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536).


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Jia Liu ◽  
Yanjin Hu ◽  
Yuan Xu ◽  
Yumei Jia ◽  
Li Miao ◽  
...  

Aims. The present study assessed the therapeutic effect of exenatide and metformin as the initial therapy on overweight/obese patients with newly diagnosed type 2 diabetes (T2D). Methods. The prospective, nonrandomized, interventional study enrolled a total of 230 overweight or obese patients with newly diagnosed T2D who were administrated exenatide or metformin hydrochloride for 12 weeks. Results. 224/230 patients, including 106 in the exenatide group and 118 in the metformin group, completed the 12-week treatment. Both exenatide and metformin significantly decreased the HbA1c levels in overweight/obese patients with newly diagnosed T2D (all P<0.05). The reduction in HbA1c and the proportion of patients with HbA1c < 7.0% (53 mmol/mol) were higher in the exenatide group than in the metformin group (all P<0.05). The exenatide treatment caused a greater decline in the body weight and BMI as compared to the metformin treatment (all P<0.01). The exenatide treatment (β = 0.41, P<0.01) and baseline HbA1c level (β = −0.84, P<0.01) were independent influencing factors for the decrease in HbA1c level. Conclusions. For an initial therapy in overweight/obese patients with newly diagnosed T2D, exenatide causes a better glycemic control than metformin. This trial is registered with NCT03297879.


Author(s):  
Brenda Bongaerts ◽  
Bianca Kollhorst ◽  
Oliver Kuss ◽  
Iris Pigeot ◽  
Wolfgang Rathmann

Abstract Aims To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany. Materials and methods Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment. Results A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment. Conclusions Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.


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