Clinical trial NCT06909006: Semaglutide Treatment in Type 1 Diabetes
Official title: Obesity and Semaglutide in Type 1 Diabetes Therapy: A Multicentre, Randomised, Double-Blinded, Placebo-Controlled, Investigator-Initiated Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Obesity in Diabetes
Obesity/Therapy
Type 1 Diabetes Mellitus (T1DM)
Insulin Sensitivity/Resistance
Semaglutide
Lipidomics
Metabolomics
Weight Loss
Glycemic Control for Diabetes Mellitus
Keywords: Semaglutide
Obesity
Type 1 Diabetes
Obese Type 1 Diabetics
Insulin sensitivity
Insulin resistance
Weight loss
GLP1-RA
GLP1
Wegovy
Lead sponsor: Nordsjaellands Hospital
Sponsor class: OTHER
Collaborators: name: Steno Diabetes Center Copenhagen
name: Steno Diabetes Center Odense
name: Zealand University Hospital
name: Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital
First posted: 2025-04-03
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, double-blinded, placebo-controlled.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Body weight
timeFrame: 74 weeks
Secondary outcomes:
measure: Systolic blood pressure
timeFrame: 74 weeks
measure: Diastolic blood pressure
timeFrame: 74 weeks
measure: Resting heart rate
timeFrame: 74 weeks
measure: Waist circumference
timeFrame: 74 weeks
measure: Hip-waist-ratio
timeFrame: 74 weeks
measure: Hemoglobin
timeFrame: 74 weeks
measure: Leucocytes
timeFrame: 74 weeks
measure: Thrombocytes
timeFrame: 74 weeks
measure: HbA1c
timeFrame: 74 weeks
measure: Fasting plasma-glucose
timeFrame: 74 weeks
measure: Fasting c-peptide
timeFrame: 74 weeks
measure: Total cholesterol
timeFrame: 74 weeks
measure: HDL cholesterol
timeFrame: 74
measure: LDL cholesterol
timeFrame: 74 weeks
measure: VLDL cholesterol
timeFrame: 74 weeks
measure: Triglycerides
timeFrame: 74 weeks
measure: non-HDL cholesterol
timeFrame: 74 weeks
measure: Sodium
timeFrame: 74 weeks
measure: Potassium
timeFrame: 74 weeks
measure: Creatinine/eGFR
timeFrame: 74 weeks
measure: Alanine transaminase (ALT)
timeFrame: 74 weeks
measure: Aspartate transaminase (AST)
timeFrame: 74 weeks
measure: Fibrosis-4-score (Fib-4)
timeFrame: 74 weeks
measure: Amylase
timeFrame: 74 weeks
measure: Lipase
timeFrame: 74 weeks
measure: High sensitivity C-reactive protein (hsCRP)
timeFrame: 74 weeks
measure: Albumin
timeFrame: 74 weeks
measure: Ketones
timeFrame: 74 weeks
measure: CGM data - Time in range (TIR)
timeFrame: 68 weeks
measure: CGM data - Time in tight range (TITR)
timeFrame: 68 weeks
measure: CGM data - Time above range (TAR)
timeFrame: 68 weeks
measure: CGM data - Time below range (TBR)
timeFrame: 68 weeks
measure: CGM data - coefficient of variation (CV)
timeFrame: 68 weeks
measure: Total daily dose of insulin
timeFrame: 74 weeks
measure: Insulin sensitivity
timeFrame: 68 weeks
measure: Fat percentage
timeFrame: 68 weeks
measure: Lean mass
timeFrame: 68 weeks
measure: Bone density (through bone mineral content)
timeFrame: 68 weeks
measure: Omics / Metabolome
timeFrame: 74 weeks
measure: Muscle tissue biopsy
timeFrame: 68 weeks
measure: Fat tissue biopsy
timeFrame: 68 weeks
measure: Electrocardiogram
timeFrame: 68 weeks
Other outcomes:
measure: Patient reported outcome measures - Dietary patterns
timeFrame: 74 weeks
measure: Patient reported outcome measures - Diabetes treatment satisfaction
timeFrame: 74 weeks
measure: Patient reported outcome measures - Diabetes distress
timeFrame: 74 weeks
measure: Adverse events
timeFrame: 74 weeks
Locations:
city: Hillerød
country: Denmark
facility: Nordsjaellands Hospital
Study officials:
affiliation: Nordsjaellands Hospital
name: Thomas F Dejgaard, MD, ph.d., endocrinologist
role: STUDY_CHAIR
References: