scholarly journals Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes

2015 ◽  
Vol 33 (4) ◽  
pp. 511-514 ◽  
Author(s):  
T. Dujic ◽  
A. Causevic ◽  
T. Bego ◽  
M. Malenica ◽  
Z. Velija-Asimi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Gastrointestinal Side Effects ◽  
Organic Cation Transporter 1

scholarly journals Variation in the plasma membrane monoamine transporter (PMAT, encoded in SLC29A4) and organic cation transporter 1 (OCT1, encoded in SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes: an IMI DIRECT study

2018 ◽  
Author(s):  
Adem Y Dawed ◽  
Kaixin Zhou ◽  
Nienke van Leeuwen ◽  
Anubha Mahajan ◽  
Neil Robertson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Membrane ◽  
Side Effects ◽  
Logistic Regression Model ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Gastrointestinal Intolerance ◽  
Gastrointestinal Side Effects ◽  
Organic Cation Transporter 1

AbstractObjectives20-30% of patients with metformin treated type 2 diabetes experience gastrointestinal side effects leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localised high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin into the circulation via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe GI side effects.Research Design and MethodsThe study included 286 severe metformin intolerant and 1128 tolerant individuals from the IMI DIRECT consortium. We assessed the association of patient characteristics, concomitant medication and the burden of mutations in the SLC29A4 and SLC22A1, genes that encode PMAT and OCT1, respectively, on odds of metformin intolerance using a logistic regression model.ResultsWomen (p < 0.001) and older people (p < 0.001) were more likely to develop metformin intolerance. Concomitant use of metformin transporter inhibiting drugs increased the odds of intolerance by more than 70% (OR = 1.72 [1.26-2.32], p < 0.001). In a logistic regression model adjusted for age, sex, weight and population substructure, the G allele at rs3889348 (SLC29A4) was associated with GI intolerance (OR = 1.34[1.09-1.65], p = 0.005). rs3889348 is the top cis-eQTL for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with metformin transporter inhibiting drugs had over three times higher odds of intolerance compared to carriers of no G allele and not treated with inhibiting drugs (OR = 3.23 [1.71-6.39], p < 0.001). Using a genetic risk score (GRS) derived from SLC29A4 (rs3889348) and previously reported SLC22A1 variants (M420del, R61C, G401S), the odds of intolerance was more than twice in individuals who carry three or more risk alleles compared with those carrying none (OR = 2.15 [1.20-4.12], p = 0.01).ConclusionsThese results suggest that intestinal metformin transporters and concomitant medications play an important role in gastrointestinal side effects of metformin.

scholarly journals Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes

Medicine ◽  
2018 ◽  
Vol 97 (27) ◽  
pp. e11349 ◽  
Author(s):  
Edith Pascale Mofo Mato ◽  
Magellan Guewo-Fokeng ◽  
M. Faadiel Essop ◽  
Peter Mark Oroma Owira
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Polymorphisms ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Metformin Therapy ◽  
Organic Cation Transporter 1

scholarly journals Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study

Diabetes ◽  
2014 ◽  
Vol 64 (5) ◽  
pp. 1786-1793 ◽  
Author(s):  
Tanja Dujic ◽  
Kaixin Zhou ◽  
Louise A. Donnelly ◽  
Roger Tavendale ◽  
Colin N.A. Palmer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 1

scholarly journals The Importance of Reducing Hyperglycemia While Preserving Insulin Secretion—The Rationale for Sodium-coupled Glucose Co-transporter 2 Inhibition in Diabetes

2009 ◽  
Vol 05 (01) ◽  
pp. 75 ◽  
Author(s):  
Serge A Jabbour ◽  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Side Effects ◽  
Sglt2 Inhibitors ◽  
Serious Adverse Events ◽  
Gastrointestinal Side Effects ◽  
Important Addition

The prevalence of type 2 diabetes continues to rise in a number of countries, presenting a need for additional effective therapeutic options to be developed. This condition has often been treated with medications that can lead to hypoglycemia (sulfonylureas), weight gain (thiazolidinediones), or other side effects, including the gastrointestinal side effects sometimes experienced with metformin. Sodium-coupled glucose co-transporter 2 (SGLT2) inhibitors are a novel class of drugs under investigation that target the kidney’s ability to reabsorb glucose into the bloodstream, improving glycemic control and aiding weight loss without inducing hypoglycemia. These compounds have shown encouraging results in several studies without any serious adverse events. They could therefore potentially become an important addition to the currently available diabetes treatments.

The Polymorphic Variants rs3088442 and rs2292334 in the Organic Cation Transporter 3 (OCT3) Gene and Susceptibility Against Type 2 Diabetes: Role of their Interaction

2017 ◽  
Vol 48 (2) ◽  
pp. 162-168 ◽  
Author(s):  
Abdolkarim Mahrooz ◽  
Ahad Alizadeh ◽  
Mohammad Bagher Hashemi-Soteh ◽  
Maryam Ghaffari-Cherati ◽  
Seyyedeh Raheleh Hosseyni-Talei
Keyword(s):  
Type 2 Diabetes ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Polymorphic Variants ◽  
Organic Cation Transporter 3
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