The GAPSID Study - How GLP-1 Analogues Prevent Steroid-Induced Diabetes

TITLE: How GLP-1 Analogues prevent steroid-induced diabetes (The GAPSID Study) DESIGN: A double-blind study evaluating how GLP-1 analogues, compared with metformin, prevent hyperglycaemia in response to a 7-day course of dexamethasone (DEX) 6 mg once daily. This is a mechanistic experimental medicine study. AIMS: To evaluate the mechanisms by which GLP-1 analogues reduce steroid-induced hyperglycaemia compared to metformin. OUTCOME MEASURES: * Primary: Glucose tolerance in response to standardised mixed meal test (MMT) lasting for 240 minutes, measured in all participants at baseline and on day 7 DEX. * Secondary: Indices of insulin resistance (M-value), beta-cell function (acute insulin response to glucose) and disposition, as measured by a combined IV glucose tolerance test and hyperinsulinaemic-euglycaemic clamp, performed at baseline and on day 7 DEX. * Exploratory: Tissue specific changes in adipose AMPK determined from adipose and muscle biopsies, taken from a subset of approximately 8 individuals in each group. ELIGIBILITY: People living with pre-diabetes or lifestyle controlled diabetes STUDY DURATION: This study will take place over 3 weeks for each partcipant. Study procedures include 10 days of baseline continuous glucose monitoring (CGM) followed by 7 days of dexamethasone with GLP-1, metformin or placebo. Participants will attend a follow-up visit 3-5 days after completing the 7-day course of study drug. The study will run over a period of 3 years. ANTICIPATED IMPACT: Mechanistic evidence for the use of GLP-1 analogues, compared with metformin, in the treatment of steroid-induced diabetes.