Semaglutide Treatment in Type 1 Diabetes (OBES1TY)

Obesity and Semaglutide in Type 1 Diabetes Therapy: A Multicentre, Randomised, Double-Blinded, Placebo-Controlled, Investigator-Initiated Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Weight Loss; Insulin Sensitivity/Resistance; Semaglutide; Metabolomics; Obesity in Diabetes; Obesity/Therapy; Type 1 Diabetes Mellitus (T1DM); Lipidomics; Glycemic Control for Diabetes Mellitus
• Intervention / Treatment: Drug: Semaglutide 2.4mg; Drug: Semaglutide placebo

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 Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thomas F Dejgaard, MD, ph.d., endocrinologist; Phone Number: 0045 26 79 61 03; Email: Thomas.fremming.dejgaard@regionh.dk
• Study Contact Backup: Name: Hasan I Mirza, MD, ph.d.-student; Phone Number: 0045 42 37 58 40; Email: hasan.imran.mirza@regionh.dk

Study Locations

• Denmark
  • Hillerød, Denmark, 3400
    • Nordsjaellands Hospital
    • Contact: Thomas F Dejgaard, MD, ph.d., endocrinologist; Phone Number: 0045 26 79 61 03; Email: Thomas.fremming.dejgaard@regionh.dk
    • Contact: Hasan I Mirza, MD, ph.d.-student; Phone Number: 0045 42 37 58 40; Email: hasan.imran.mirza@regionh.dk
    • Principal Investigator: Thomas F Dejgaard, MD, ph.d., endocrinologist
    • Sub-Investigator: Hasan I Mirza, MD, ph.d.-student

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

• Treated with GLP1-RAs within last 6 months
• Known intolerance for semaglutide
• 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 or unless basocellular carcinomas
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Semaglutide; 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	Drug: Semaglutide 2.4mg; The active comparator of the intervention is s.c. Semaglutide injection once a week in increasing doses every month from 0.25 mg to 0.5 mg to 1.0 mg to 1.7 mg to 2.4 mg and the placebo comparator is s.c. injection with a visually identical and same label pen as described for the active comparator; Other Names: Active semaglutide
Placebo Comparator: Semaglutide placebo; Visually identical injector pen without the active comparator.	Drug: Semaglutide placebo; Visually identical and same label as the active comparator intervention; Other Names: Placebo semaglutide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	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.	74 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure	Systolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.	74 weeks
Diastolic blood pressure	Diastolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.	74 weeks
Resting heart rate	Systolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.	74 weeks
Waist circumference	Waist circumference will be assessed and evaluated for changes during and after treatment for 68 weeks with semaglutide compared to before treatment.	74 weeks
Hip-waist-ratio	Hip-waist-ratio will be assessed and evaluated for changes during and after treatment for 68 weeks with semaglutide compared to before treatment.	74 weeks
Hemoglobin	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.	74 weeks
Leucocytes	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.	74 weeks
Thrombocytes	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.	74 weeks
HbA1c	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.	74 weeks
Fasting plasma-glucose	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.	74 weeks
Fasting c-peptide	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.	74 weeks
Total cholesterol	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.	74 weeks
HDL cholesterol	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.	74
LDL cholesterol	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.	74 weeks
VLDL cholesterol	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.	74 weeks
Triglycerides	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.	74 weeks
non-HDL cholesterol	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.	74 weeks
Sodium	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.	74 weeks
Potassium	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.	74 weeks
Creatinine/eGFR	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.	74 weeks
Alanine transaminase (ALT)	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.	74 weeks
Aspartate transaminase (AST)	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.	74 weeks
Fibrosis-4-score (Fib-4)	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.	74 weeks
Amylase	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.	74 weeks
Lipase	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.	74 weeks
High sensitivity C-reactive protein (hsCRP)	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.	74 weeks
Albumin	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.	74 weeks
Ketones	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	74 weeks
CGM data - Time in range (TIR)	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.	68 weeks
CGM data - Time in tight range (TITR)	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.	68 weeks
CGM data - Time above range (TAR)	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.	68 weeks
CGM data - Time below range (TBR)	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.	68 weeks
CGM data - coefficient of variation (CV)	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.	68 weeks
Total daily dose of insulin	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.	74 weeks
Electrocardiogram	Electrocardiograms (ECG) will be recorded at initiation and end of treatment period to assess and evaluate if any rhytm changes occur.	68 weeks
Insulin sensitivity	For a subgroup consisting of the first 40 patients from two specified sites: Insulin sensitivity will be assessed through the golden standard hyperinsulinemic euglycemic clamping method. This will be done before treatment and at the end of treatment.	68 weeks
Fat percentage	For a subgroup consisting of the first 40 patients from two specified sites: The fat percentage is measured by DXA scan at randomisation and at end-of-treatment.	68 weeks
Lean mass	For a subgroup consisting of the first 40 patients from two specified sites: Lean body mass is measured by DXA scan at randomisation and at end-of-treatment.	68 weeks
Bone density (through bone mineral content)	For a subgroup consisting of the first 40 patients from two specified sites: Bone density (through bone mineral content) is measured by DXA scan at randomisation and at end-of-treatment.	68 weeks
Omics / Metabolome	For a subgroup consisting of the first 40 patients from two specified sites: Blood samples will be analyzed to assess metabolomic profile (entailing both lipidome and proteome) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up	74 weeks
Muscle tissue biopsy	For a subgroup consisting of the first 40 patients from two specified sites: Muscle tissue biopsies will be taken to assess changes in transcriptome at randomisation and at end-of-treatment.	68 weeks
Fat tissue biopsy	For a subgroup consisting of the first 40 patients from two specified sites: Fat tissue biopsies will be taken to assess changes in transcriptome at randomisation and at end-of-treatment.	68 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported outcome measures - Dietary patterns	Questionnaires (DNBCs FFQ) will be analyzed to evaluate changes in dietary patterns before treatment, throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.	74 weeks
Adverse events	Tolerability will be assessed through standardized adverse event reporting (including episodes of hypoglycemia) throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.	74 weeks
Patient reported outcome measures - Diabetes treatment satisfaction	Questionnaires (DTSQ-s and DTSQ-c) will be analyzed to evaluate changes in diabetes treatment satisfaction before treatment, throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.	74 weeks
Patient reported outcome measures - Diabetes distress	Questionnaires (PAID) will be analyzed to evaluate changes in diabetes treatment satisfaction before treatment, throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.	74 weeks

Collaborators and Investigators

• Sponsor: Nordsjaellands Hospital
• Collaborators: Zealand University Hospital; Steno Diabetes Center Copenhagen; Steno Diabetes Center Odense; Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital
• Investigators: Study Chair: Thomas F Dejgaard, MD, ph.d., endocrinologist, Nordsjaellands Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Insulin resistance; Semaglutide; Weight loss; Type 1 Diabetes; Insulin sensitivity; GLP1; Wegovy; GLP1-RA; Obese Type 1 Diabetics
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Autoimmune Diseases; Immune System Diseases; Body Weight Changes; Glucose Metabolism Disorders; Hyperinsulinism; Overweight; Obesity; Weight Loss; Hypersensitivity; Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Resistance; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: U1111-1304-0713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared upon request for it.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No