There are 3 clinical trials
Gliclazide has greater glucose lowering efficacy than glibenclamide among type 2 diabetes mellitus patients with minor haplotype (K23/A1369) at the KCNJ11/ABCC gene locations.
Interestingly, the KCNJ11 E23K (rs5219) variant was shown to confer susceptibility to T2DM and the ABCC8 S1369A (rs757110) variant was found to be in complete linkage disequilibrium with it i.e. inherited together as a genetic block (haplotype). --- E23K ---
Description: Glycemic variability will be assessed using the EasyGV software (http://www.phc.ox.ac.uk/research/diabetes/software/easygv/) which is capable of calculating 10 different measures of glycemic variability from continuous glucose monitoring data, such as Standard Deviation (SD) and M-value, mean amplitude of glycemic excursions (MAGE).
Measure: Glycemic variability Time: 6 daysThe Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. A matched clamp consists of an of oral glucose tolerance test followed by an isoglycaemic intravenous glucose infusion (IGII). The study will investigate whether there is synergy between a physiological sulphonylurea (SU) stimulus and the incretin effect, causing augmentation of insulin secretion in patients with type 2 diabetes mellitus (T2DM). The study will take place at The Clinical Research Centre at Ninewells Hospital in Dundee over five visits. It will evaluate 20 patients with T2DM on no diabetes therapy, or metformin monotherapy. All participants will undergo two matched clamps. The first matched clamp will be with no intervention. The second intervention matched clamp, low-dose liquid gliclazide will be administered 1-hour prior to each test. The sulphonylurea, Gliclazide, in this this instance will be used as a physiological stimulus and will only be given on two occasions as part of the second matched clamp. The first eight participants will participate in the dose-ranging phase. They will receive either 10mg or 20mg gliclazide as a stimulus to augment the incretin effect. A further twelve participants will then be recruited to complete the study utilising the dose which caused the greatest increment in insulin secretion. LOGIC will also evaluate the cohort for effect of KCNJ11 genotype on physiological response.
Insulin secretory response analysed by KCNJ11 Genotype (E23K, E23E, K23K). --- E23K ---
insulin secretory response for E23K, E23E, K23K variants.. Inclusion Criteria: - Age 40 - 80, - Age of Diabetes Diagnoses ≥ 35 - T2DM on no treatment or metformin monotherapy - White British - HbA1c ≤ 8% (64mmol/mol) - eGFR ≥ 50ml/min-1 - ALT ≤ 2.5 x ULN - Able to consent Exclusion Criteria: - Type 1 Diabetes Mellitus - HbA1c > 8.0% (> 64mmol/mol) - eGFR <50ml/min-1 - ALT >2.5 x ULN - Anaemia (Haemoglobin <12.0 g/dL for women, <13.0 g/dL for men) - Pregnancy, lactation or a female planning to conceive within the study period - Established pancreatic disease - Participating in clinical phase of another interventional trial/study or have done so within the last 30 days - Any other significant medical reason for exclusion as determined by the investigator Inclusion Criteria: - Age 40 - 80, - Age of Diabetes Diagnoses ≥ 35 - T2DM on no treatment or metformin monotherapy - White British - HbA1c ≤ 8% (64mmol/mol) - eGFR ≥ 50ml/min-1 - ALT ≤ 2.5 x ULN - Able to consent Exclusion Criteria: - Type 1 Diabetes Mellitus - HbA1c > 8.0% (> 64mmol/mol) - eGFR <50ml/min-1 - ALT >2.5 x ULN - Anaemia (Haemoglobin <12.0 g/dL for women, <13.0 g/dL for men) - Pregnancy, lactation or a female planning to conceive within the study period - Established pancreatic disease - Participating in clinical phase of another interventional trial/study or have done so within the last 30 days - Any other significant medical reason for exclusion as determined by the investigator Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 The Study of Sulphonylurea Synergy with Incretins (LOGIC) is a Proof-of-Concept Physiological study in the form of two matched isoglycaemic clamps. --- E23K ---
Description: Comparison of two matched clamps (oral glucose tolerance test + isoglycaemic intravenous glucose infusion). Matched clamp 1 - control. Matched clamp 2 - low dose gliclazide. Levels of insulin/c-peptide, incretin hormones and plasma glucose will be compared in the presence and absence of low dose gliclazide
Measure: Difference in insulin secretion and incretin effect between two matched clamps (presence and absence of low dose gliclazide) Time: Through four study visits completed over 4 weeksDescription: Difference in insulin secretory response to low dose gliclazide calculated by insulin/cpeptide levels in matched clamp(gliclazide). Differences will then be compared by participants genotype e.g. insulin secretory response for E23K, E23E, K23K variants.
Measure: Insulin secretory response analysed by KCNJ11 Genotype (E23K, E23E, K23K) Time: Through four study visits completed over 4 weeksThe SUGAR-MGH investigators are studying the influence of inherited gene variants on the response to two commonly prescribed type 2 diabetes medications, metformin and glipizide. They hypothesize that variants in genes that are associated with type 2 diabetes or related traits may impact the effect of anti-diabetic medications. In addition, physiological responses to an insulin secretagogue or an insulin sensitizer may shed light on the mechanism of action of reported genetic associations.
In particular, sulfonylureas may have differential effects on individuals depending on the allelic variant they carry at KCNJ11 E23K; conversely, because TCF7L2 is postulated to influence insulin secretion by regulating the action of glucagon-like peptide 1 (GLP-1), and sulfonylureas act at a different step in the insulin secretion pathway, the effect of sulfonylureas on insulin secretion could be independent of genetic variation at TCF7L2. --- E23K ---
Description: Investigators will measure insulin and glucose levels for 240 minutes after Glipizide administration on Visit 1, and compare them by genotype at selected loci.
Measure: Glipizide response Time: Between 0-240 minutes, Visit 1Description: Investigators will measure the change in glycemic measures between Visit 1 and Visit 2 as an index of Metformin response, and compare them by genotype at selected loci.
Measure: Metformin response Time: 7 daysDescription: Investigators will measure GLP-1 and GIP during the 120 minutes of Visit 2, and compare them by genotype at selected loci.
Measure: Incretin levels Time: 120 minutes, Visit 2Description: Investigators will measure proinsulin and glucagon levels at regular intervals during Visits 1 and 2, and compare them by genotype at selected loci.
Measure: Proinsulin, glucagon Time: 7 daysDescription: Investigators will perform metabolomic profiling of plasma samples at regular intervals in Visits 1 and 2, by using initially a targeted approach on an existing platform that measures ~400 metabolites (both polar and non-polar); they will compare their relative concentrations by genotype at selected loci before and after the interventions.
Measure: Metabolomics Time: 7 daysDescription: Investigators will measure 25-hydroxy vitamin D levels at baseline, and examine its effects on glycemic measures during Visits 1 and 2.
Measure: Vitamin D Time: Baseline