The Study of Sulphonylurea Synergy with DPP4 Inhibitors (SSS Study) will establish whether a very low dose of sulphonylurea will have a synergistic role on augmentation of insulin secretion when given in combination with a DPP4 inhibitor as a primary outcome. The study will recruit 30 patients with type 2 diabetes mellitus controlled with no treatment or metformin monotherapy with an HbA1c <64mmol/mol (<8%). In this unblinded, randomised physiological study, participants will receive four 14-day intervention blocks: low dose sulphonylurea alone, DPP4 inhibitor alone, low dose sulphonylurea + DPP4 inhibitor or no treatment change. The primary outcome will be assessed through evaulation of insulin secretion and sensitivity at mixed meal test at the end of each treatment block. Glycaemic variability on continuous glucose monitoring for each intervention block will be evaluated as a secondary outcome. In addition, the primary outcome will be evaulated for KCNJ11 genotype as an additional secondary outcome.
Name: DPP4 Inhibitor
Description: Comparison of four mixed meal tests performed at the end of each intervention block. Meal tests will evaluate 1) No intervention 2) Low dose sulphonylurea alone 3) DPP4 inhibitor alone 4) Low dose sulphonylurea + DPP4 inhibitor. Measures of the incretin effect will be compared between the different blocks.Measure: Difference in incretin effect between mixed meal tests Time: Through four mixed meal tests which take place at the end of each 14 day intervention block. The four intervention blocks will be completed during an 8 week clinical phase of study.
Description: Difference in insulin secretory response to low dose gliclazide calculated by insulin/cpeptide levels in each meal test visit. 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 Time: Through 4 meal test visits completed over an 8 week clinical phase of study. Outcome will also be evaluated through variability of glucose levels observed on continuous glucose monitoring worn for duration of 8 week clinical phase.
Description: Comparison time-in-range of blood sugars as low, target and high on continuous glucose monitoring between each intervention blockMeasure: Variation in blood glucose during intervention blocks analysed by continuous glucose monitoring Time: Meansurements taken via continuous glucose monitoring sensors worn by participants for duration of 8 week clinical phase
There is one SNP
insulin secretory response for E23K, E23E, K23K variants.. Variation in blood glucose during intervention blocks analysed by continuous glucose monitoring. --- E23K ---