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

Not Applicable

Recruiting

• Conditions: Steroid-Induced Diabetes; Steroid Induced Hyperglycemia
• Interventions: Drug: Semaglutide Oral Product; Drug: Metformin Oral Tablet; Drug: Placebo

• Registration Number: NCT06318442
• Lead Sponsor: Imperial College London

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-06
• Study First Submitted QC: 2024-03-12
• Study First Posted: 2024-03-19
• Study Start: 2024-05-15
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-02
• Primary Completion: 2027-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Adults ≥ 18 years;
• Male or female;
• Pre-diabetes (HbA1c ≥42 and <47 mmol/mol, or lifestyle-controlled diabetes (HbA1c ≥48 and ≤52 mmol/mol); measurements within range on two separate occasions ≥90 days apart)
• Body mass index ≥22.5 kg/m2

Exclusion Criteria

• Prior treatment with any diabetes medication within 90 days;
• Current or planned pregnancy, or current breastfeeding;
• Previous treatment with GC (topical, oral, injected) within 30 days or 90 days for extended-release injected GCs (e.g. Depo-Medrone);
• Continuing requirement for GC treatment (e.g. for steroid replacement, chronic inflammatory or immunological condition);
• Treatment with medications altering DEX pharmacokinetics (e.g. phenytoin, carbamazepine, ritonavir).
• History of pancreatitis, renal disease (eGFR <30), severe hepatic impairment, gallbladder disorders, or GI disease (e.g. IBD), heart failure, history of medullary thyroid cancer (MTC), or previous skin reactions.
• History of bleeding disorders of anticoagulant therapies (exclusion from the biopsy substudy only)
• History of giving blood or having taken part in another non-related study in the last three months
• History of any other medical, psychological condition, or use of any medications, which, in the opinion of the investigators, would either interfere with the study or compromise the safety of the participant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Once daily semaglutide	Semaglutide Oral Product	Once daily semaglutide 3 mg (uptitrated to 3 mg twice daily after two days).
- Metformin	Metformin Oral Tablet	Metformin modified release tablets (500mg once daily for the first two days, then 500 mg twice daily).
Placebo	Placebo	Placebo tablets

Primary Outcome Measures

Name	Time	Method
Difference in Glucose tolerance	Through study completion, on day 7 dexamethasone and study medication	Glucose tolerance as measured by glucose area under the curve (AUC), in response to standardised mixed meal test (MMT) lasting for 240 minutes. This will be measured in all participants at baseline and at the end of the study medication period (after 7 days of dexamethasone and study medication).

Secondary Outcome Measures

Name	Time	Method
Difference in insulin secretion	Day 6 of dexamethasone and study medication	This will be measured by the acute insulin response to glucose based on the incremental AUC for insulin during the first 10 minutes of an IVGTT and the second phase insulin response based on incremental AUC for insulin during +10 to +60 minutes.; This will be measured in a subset of patients (10 from each randomisation group), performed at baseline and on day 6 of dexamethasone and study medication
Difference in insulin sensitivity	Day 6	This will be measured by the disposition index. This will be calculated as the product of the AIRg and M value during the combined IVGTT and hyperinsulinaemic-euglycaemic clamp.; This will be measured in a subset of patients (10 from each randomisation group), performed at baseline and on day 6 of dexamethasone and study medication.

Trial Locations

Locations (1)

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom