The influence of SLC22A1 rs622342 and ABCC8 rs757110 genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian patients with type 2 diabetes

Abstract

Background: The incidence of Type 2 Diabetes Mellitus (T2DM) in Egypt is considered one of the highest in the world. Metformin and Sulfonylureas are usually prescribed together due to their efficacy and their relatively low cost. Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action. Sulfonylureas enhance insulin release from pancreatic B- cells through binding to sulfonylurea receptor 1, encoded by ABCC8 gene. Single nucleotide polymorphisms in the SLC22A1 and ABCC8 genes might affect the response of each drug. Aims: To investigate the influence of SLC22A1 rs622342 (A>C) and ABCC8 rs757110 (A>C) genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian T2DM patients. Methods: Observational cross-sectional study in which patients receiving metformin and glimepiride combination therapy for at least 6 months were included for genotyping and classified into either responders or non-responders, based on their HbA1C level. Results: A total of 127 patients were included and genotyped. They were divided into 93 responders (HbA1C<7%) and 34 non-responders (HbA1C≥7%). Minor allele frequencies for rs622342 and rs757110 were 0.189 and 0.271, respectively. Only SLC22A1 rs622342 variant was found to be associated with the response of combination therapy, in which AA alleles carriers were 2.7-times more responsive to metformin than C allele carriers (Recessive model, odds ratio = 2.718, p = 0.025, 95% CI = 1.112–6.385). Conclusion: Genotyping of rs622342 can be useful in predicting the response to metformin in combination therapy in Egyptian T2DM patients.

Single Nucleotide Polymorphisms Associated with Metformin and Sulphonylureas’ Glycaemic Response among South African Adults with Type 2 Diabetes Mellitus

“…Furthermore, Naja et al [ 29 ] showed that Lebanese carriers of the AC or the AA genotype exhibited better glycaemic control in individuals with T2DM undergoing metformin/SU combination therapy. Similar effects were observed among Egyptian patients of T2DM [ 34 ]. These findings warrant the use of this polymorphism as a predictor of metformin/SU efficacy among patients of African origin with T2DM.…”

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

“…In addition, Umamaheswaran et al, who studied rs622342 on Indian population, showed that AA patients had a 5.6 times better chance to respond to metformin treatment when compared to CC patients [ 20 ]. Similarly, Reséndiz et al, who studied rs622342 on Mexican population, showed that CC genotype is significantly associated with an increase in HbA1c levels during the follow-up period [ 21 ], and Ebid et al showed in an Egyptian population that carriers of the A allele of rs622342 were more responsive to metformin in combination therapy than C allele carriers [ 22 ].…”

Impact of a Clinical Pharmacist Intervention Program on the Follow-up of Type-2 Diabetic Patients

“…That number was predicted to be doubled by 2045, and Egypt will climb to number 6th rank in the top 10 list. 8,9 There are no formal referral systems in the ministry of Health of Egypt in a delivery system, and most patients with diabetes are either treated in the private clinics through out-of-pocket fee for service, in the limited number of academic hospitals, or in the scarce dedicated diabetes centers in Cairo and some other major hospitals. According to the IDF, the current spending on diabetes in Egypt is among the lowest in the Middle-East and North Africa (MENA) at $116 per patient per year.…”

“…Diabetes is also the major cause of end-stage renal disease (ESRD) and leg amputation in Egypt. 9 Therefore DM progression and complication control are some of the important components for DM management in healthcare programs. 10…”