Semaglutide Treatment in Type 1 Diabetes

Phase 3

Not yet recruiting

• Conditions: Obesity in Diabetes; Obesity/therapy; Type 1 Diabetes Mellitus (T1DM); Insulin Sensitivity/Resistance; Semaglutide; Lipidomics; Metabolomics; Weight Loss; Glycemic Control for Diabetes Mellitus
• Interventions: Drug: Semaglutide 2.4mg; Drug: Semaglutide placebo

• Registration Number: NCT06909006
• Lead Sponsor: Nordsjaellands Hospital

Brief Summary

The goal of this clinical trial is to investigate the efficacy of semaglutide on body weight, insulin dose requirements and improvements in glucose control and safety aspects in regards to risk of hypoglycemia and diabetic ketoacidosis for patients with established Type 1 Diabetes.

Detailed Description

This is a multicentre, randomised, double-blinded, placebo-controlled and investigator-initiated trial aimed to investigate the efficacy of semaglutide in patients with Type 1 Diabetes.

Patients from all included diabetes care centres will at routine visits be screened for eligibility for the trial and offered participation. If accepted, the patients will be randomised to one of two intervention arms and undergo a series of different examinations prior to start of the intervention.

The two arms consist of treatment with subcutaneous semaglutide injections or subcutaneous injections with semaglutide placebo. The baseline examinations entail documentation of insulin doses, dietary patterns, diabetes distress and treatment satisfaction questionnaires, anthropoimetric data (height, weight and calculation of BMI, waist circumference, waist-hip-ratio), blood work (HbA1c, fasting glucose, fasting c-peptide, lipids, liver and kidney markers incl. Fib-4-scoring, hematology, hsCRP), ECG, capturing of data from continuous/flash glucose monitors.

The first 40 included in the study from the centres of SDCA and NOH will further be examined through hyperinsulinemic euglycemic clamps to determine their insulin sensitivity and asses their transcriptome through muscle and fat cell biopsies in relation to the clamp and also be assessed through DXA scans to look at body composition and bone density.

Patients will then be handed out their trial drug-pens and start the uptitration proces.

The efficacy of semaglutide will be evaluated through the above mentioned array of different investigations by comparing parameters prior to trial drug start, during (throughout the study period), at the end of the drug and at a 6 week post-study followup in an intention-to-treat analysis primarily and secondarily a per-protocol analysis.

The safety will be assessed through evaluation of standardized adverse event reporting (including hypoglycemic events and diabetic ketoacidosis).

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-17
• Study First Submitted QC: 2025-03-26
• Last Update Submitted: 2025-03-26
• Study First Posted: 2025-04-03
• Last Update Posted: 2025-04-03
• Study Start: 2025-10
• Primary Completion: 2028-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 122

Inclusion Criteria

• Type 1 Diabetes for more than 3 years
• BMI ≥ 30 or ≥ 27 and atleast one comorbidity (hypertension, hypercholesterolemia, microalbuminuria, ischemic heart disease, history of stroke, atherosclerosis or arthrosis

Exclusion Criteria

• Other forms of diabetes
• Pregnant or nursing women
• Fertile women not using chemical (hormonal) or mechanical (spiral) contraceptives
• Liver disease with elevated plasma alanine aminotransferase (ALT) > five times and plasma aspartate aminotransferase (AST) > five times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
• Acute or chronic pancreatitis
• Cancer, unless in complete remission for > 5 years
• History of thyroid adenoma or carcinoma
• Alcohol/drug abuse
• Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation
• Receipt of an investigational drug within 30 days prior to visit 0 / Simultaneous participation in any other clinical intervention trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semaglutide	Semaglutide 2.4mg	Subcutaneous injection through injector pen with the active comparator Semaglutide once a week in monthly increasing doses as given: 0.25mg - 0.5mg - 1.0mg - 1.7mg - 2.4mg
Semaglutide placebo	Semaglutide placebo	Visually identical injector pen without the active comparator.

Primary Outcome Measures

Name	Time	Method
Body weight	74 weeks	Body weight will be measured both prior to and following treatment for 68 weeks with either semaglutide or placebo. Changes in body weight will be compared for the two intervention arms, before, throughout and at the end of treatment and then at followup 6 weeks later.

Secondary Outcome Measures

Name	Time	Method
Systolic blood pressure	74 weeks	Systolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.
Diastolic blood pressure	74 weeks	Diastolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.
Resting heart rate	74 weeks	Systolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.
Waist circumference	74 weeks	Waist circumference will be assessed and evaluated for changes during and after treatment for 68 weeks with semaglutide compared to before treatment.
Hip-waist-ratio	74 weeks	Hip-waist-ratio will be assessed and evaluated for changes during and after treatment for 68 weeks with semaglutide compared to before treatment.
Hemoglobin	74 weeks	Blood samples will be analyzed to assess hemoglobin before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Leucocytes	74 weeks	Blood samples will be analyzed to assess leucocytes levels before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Thrombocytes	74 weeks	Blood samples will be analyzed to assess thrombocytes levels before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
HbA1c	74 weeks	Blood samples will be analyzed to assess HbA1c before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Fasting plasma-glucose	74 weeks	Blood samples will be analyzed to assess fasting plasma-glucose before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Fasting c-peptide	74 weeks	Blood samples will be analyzed to assess fasting c-peptide before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Total cholesterol	74 weeks	Blood samples will be analyzed to assess total cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
HDL cholesterol	74	Blood samples will be analyzed to assess HDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
LDL cholesterol	74 weeks	Blood samples will be analyzed to assess LDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
VLDL cholesterol	74 weeks	Blood samples will be analyzed to assess VLDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Triglycerides	74 weeks	Blood samples will be analyzed to assess triglycerides levels before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
non-HDL cholesterol	74 weeks	Blood samples will be analyzed to assess non-HDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Sodium	74 weeks	Blood samples will be analyzed to assess sodium before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Potassium	74 weeks	Blood samples will be analyzed to assess potassium before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Creatinine/eGFR	74 weeks	Blood samples will be analyzed to assess creatinine levels to calculate estimated Glomerular Filtration Rates (eGFR, based on sex, age and creatinine leve) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Alanine transaminase (ALT)	74 weeks	Blood samples will be analyzed to assess alanine transaminase (ALT) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Aspartate transaminase (AST)	74 weeks	Blood samples will be analyzed to assess aspartate transaminase (AST) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Fibrosis-4-score (Fib-4)	74 weeks	Blood samples will be analyzed for fibrosis-4-scores (based on age, thrombocytes, ALT and AST) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Amylase	74 weeks	Blood samples will be analyzed to assess pancreatic amylase before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Lipase	74 weeks	Blood samples will be analyzed to assess pancreatic lipase before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
High sensitivity C-reactive protein (hsCRP)	74 weeks	Blood samples will be analyzed to assess high sensitivity C-reactive protein (hsCRP) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Albumin	74 weeks	Blood samples will be analyzed to assess serum albumin before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Ketones	74 weeks	Blood samples will be analyzed to assess total serum ketones before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up
CGM data - Time in range (TIR)	68 weeks	Data from CGMs will be analyzed to asses time in range (TIR) before treatment and evaluated for changes in TIR throughout the 68-week regimen and at its conclusion.
CGM data - Time in tight range (TITR)	68 weeks	Data from CGMs will be analyzed to asses time in tight range (TITR) before treatment and evaluated for changes in TITR throughout the 68-week regimen and at its conclusion.
CGM data - Time above range (TAR)	68 weeks	Data from CGMs will be analyzed to asses time above range (TAR) before treatment and evaluated for changes in TAR throughout the 68-week regimen and at its conclusion.
CGM data - Time below range (TBR)	68 weeks	Data from CGMs will be analyzed to asses time in range (TBR) before treatment and evaluated for changes in TBR throughout the 68-week regimen and at its conclusion.
CGM data - coefficient of variation (CV)	68 weeks	Data from CGMs will be analyzed to asses coefficient of variation (CV) before treatment and evaluated for changes in CV throughout the 68-week regimen and at its conclusion.
Total daily dose of insulin	74 weeks	Total daily dose will be assessed at randomization and evaluated for changes throughout treatment regimen, at the end of study and at six weeks followup through the use of insulin dose diaries.
Insulin sensitivity	74 weeks	Insulin sensitivity will be assessed through the golden standard hyperinsulinemic euglycemic clamping method. This will be done before treatment, at the end of treatment and for followup six weeks later
Fat percentage	68 weeks	The fat percentage is measured by DXA scan at randomisation, after 36 weeks and at end-of-treatment.
Lean mass	68 weeks	Lean body mass is measured by DXA scan at randomisation, after 36 weeks and at end-of-treatment.
Bone density (through bone mineral content)	68 weeks	Bone density (through bone mineral content) is measured by DXA scan at randomisation, after 36 weeks and at end-of-treatment.
Omics / Metabolome	74 weeks	Blood samples will be analyzed to assess metabolomic profile (entailing both lipidome and transcriptome) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up
Electrocardiogram	68 weeks	Electrocardiograms (ECG) will be recorded at initiation and end of treatment period to assess and evaluate if any rhytm changes occur.

Trial Locations

Locations (1)

Nordsjaellands Hospital; 🇩🇰 Hillerød, Denmark