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NCT Number: NCT06318442

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.

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Key information

Conditions

Steroid-Induced Diabetes Steroid Induced Hyperglycemia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location status: Recruiting

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Semaglutide Oral Product

Drug

Oral semaglutide 3mg once uptitrated to twice daily

Metformin Oral Tablet

Drug

Metformin modified release tablets 500mg once daily uptitrated to twice daily).

Placebo

Drug

Placebo tablets

Primary outcomes

  1. Difference in Glucose tolerance

    Time frame: 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 outcomes

  1. Difference in insulin secretion

    Time frame: 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

  2. Difference in insulin sensitivity

    Time frame: Day 6

    This will be measured by the M value, based on the glucose infusion rate during the last 60 minutes of a 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

  3. Difference in insulin sensitivity

    Time frame: Day 6

    This will be measured by the M/I index, calculated by the M value divided by the mean steady state insulin levels during the last 60 minutes of a 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

  4. Difference in insulin sensitivity

    Time frame: 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.

Other outcomes

  1. Mean glucose and glycaemic variation by continuous glucose monitoring (CGM), using a validated blinded system (Dexcom G7).

    Time frame: Through study completion

    A baseline recording will be made for 10 days prior to DEX. A second 10-day recording will be made covering the 7 days of DEX and for 3 days after.

  2. Changes in fasting gut hormones

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Fasting glucose will be measured at baseline and after a 7-day course of DEX and treatment intervention.

  3. Changes in fasting gut hormones

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Fasting insulin and c-peptide levels will be measured at baseline and after a 7-day course of DEX and treatment intervention.

  4. Changes in fasting gut hormones

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Fasting glucagon levels will be measured at baseline and after a 7-day course of DEX and treatment intervention.

  5. Changes in fasting lipid profile

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Fasting lipid profiles will be measured at baseline and after a 7-day course of DEX and treatment intervention.

  6. Changes in post prandial gut hormones

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Post prandial insulin and c-peptide levels will be measured during the mixed meal test, performed at baseline and after a 7-day course of DEX and treatment intervention.

  7. Changes in post prandial gut hormones

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Post prandial glucagon levels will be measured during the mixed meal test, performed at baseline and after a 7-day course of DEX and treatment intervention.

  8. Changes in anthropometrics

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Anthropometric measurements of height and weight will be combined to report BMI kg/m2 before and after a 7-day course of DEX and treatment intervention.

  9. Changes in anthropometrics

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    Measurements of hip and waist circumference will be combined to calculate the waist:hip ratio before and after a 7-day course of DEX and treatment intervention.

  10. Tissue specific changes in AMPK determined from adipose and muscle biopsies

    Time frame: Through study completion, on day 7 dexamethasone and study medication

    This will be taken from a subset of approximately 8 individuals in each group prior to, and at the end of a 7 day course of DEX. Depending on emerging data and participant uptake, this may be subject to change.

Study contacts

Contact information is provided by the study sponsor or research team.

Katharine Lazarus, MBChB, BSc

CONTACT

[email protected]

07555717544

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Registry information

Official study title

How GLP-1 Analogues Prevent Steroid-Induced Diabetes

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Mar 19, 2024
Registry last updated
Oct 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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