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

Imperial College London

Status: Enrolling

Conditions: Steroid-Induced Diabetes; Steroid Induced Hyperglycemia

Treatments: Drug: Semaglutide Oral Product; Drug: Metformin Oral Tablet; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06318442

22HH8018

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 3 patient groups, including a placebo group

Once daily semaglutide

Experimental group

Description:

Once daily semaglutide 3 mg (uptitrated to 3 mg twice daily after two days).

Treatment:

Drug: Semaglutide Oral Product

- Metformin

Active Comparator group

Description:

Metformin modified release tablets (500mg once daily for the first two days, then 500 mg twice daily).

Treatment:

Drug: Metformin Oral Tablet

Placebo

Placebo Comparator group

Description:

Placebo tablets

Treatment:

Drug: Placebo