protocolSection identificationModule nctId: NCT06318442, orgStudyIdInfo id: 22HH8018, briefTitle: The GAPSID Study - How GLP-1 Analogues Prevent Steroid-Induced Diabetes, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-04-06, primaryCompletionDateStruct date: 2027-06-01, completionDateStruct date: 2027-06-01, studyFirstPostDateStruct date: 2024-03-19, lastUpdatePostDateStruct date: 2024-03-19, sponsorCollaboratorsModule leadSponsor name: Imperial College London, class: OTHER, descriptionModule briefSummary: 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 diabetesSTUDY 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., conditionsModule conditions: Steroid-Induced Diabetes, conditions: Steroid Induced Hyperglycemia, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: BASIC_SCIENCE, maskingInfo masking: QUADRUPLE, whoMasked: PARTICIPANT, whoMasked: CARE_PROVIDER, whoMasked: INVESTIGATOR, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 60, type: ESTIMATED, armsInterventionsModule interventions name: Semaglutide Oral Product, interventions name: Metformin Oral Tablet, interventions name: Placebo, outcomesModule primaryOutcomes measure: Difference in Glucose tolerance, secondaryOutcomes measure: Difference in insulin secretion, secondaryOutcomes measure: Difference in insulin sensitivity, secondaryOutcomes measure: Difference in insulin sensitivity, secondaryOutcomes measure: Difference in insulin sensitivity, otherOutcomes measure: Mean glucose and glycaemic variation by continuous glucose monitoring (CGM), using a validated blinded system (Dexcom G7)., otherOutcomes measure: Changes in fasting gut hormones, otherOutcomes measure: Changes in fasting gut hormones, otherOutcomes measure: Changes in fasting gut hormones, otherOutcomes measure: Changes in fasting lipid profile, otherOutcomes measure: Changes in post prandial gut hormones, otherOutcomes measure: Changes in post prandial gut hormones, otherOutcomes measure: Changes in anthropometrics, otherOutcomes measure: Changes in anthropometrics, otherOutcomes measure: Tissue specific changes in AMPK determined from adipose and muscle biopsies, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Imperial College Healthcare NHS Trust, city: London, country: United Kingdom, geoPoint lat: 51.50853, lon: -0.12574, hasResults: False