Evaluation of Semaglutide in Glycemic Control for Patients with Type 1 Diabetes and Insulin Resistance: A Randomized, Open-Label Study

The primary objective of this study is to evaluate the effect of a 6-month additional treatment with **semaglutide** in patients with type 1 diabetes and "double diabetes" on the change in the percentage of time spent within the glycemic target range (0.70-1.80 g/l) compared to standard treatment. This is clinically relevant as maintaining blood glucose levels within the target range is crucial for reducing the risk of diabetes-related complications.

Secondary objectives include assessing the impact of semaglutide on various parameters over a 6-month period compared to standard treatment in the same patient population. These parameters are:

• **HbA1c** levels
• Weight and waist circumference
• Daily dose of insulin administered
• Glycemic variability
• Occurrence of hypoglycemia
• Possible occurrence of undesirable effects
• Percentage of time spent within the glycemic target range between D0 and D90, as well as between D90 and D180

The clinical trial involves participants diagnosed with **type 1 diabetes** who also exhibit characteristics of "double diabetes." The study population includes both male and female subjects, with an age range starting from 18 years and above. Participants are required to have a body mass index (BMI) of 27 kg/m² or higher and must have been diagnosed with type 1 diabetes before the age of 35. All participants are treated with optimized insulin therapy and have undergone specific therapeutic education on insulin dose adaptation. The trial population was selected based on specific criteria, including a family history of type 2 diabetes or obesity, elevated triglycerides, and specific HDL cholesterol levels. Participants must have an HbA1c level between 7.5% and 12% in the three months prior to inclusion and must use continuous glucose monitoring systems. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effect of **semaglutide** in patients with type 1 diabetes who also exhibit characteristics of type 2 diabetes, a condition often referred to as "double diabetes." This study is a randomized, open-label trial, which means that participants will be randomly assigned to treatment groups, and both the researchers and participants will know which treatment is being administered. The trial will span a total duration of 6 months, with the primary objective being to assess the change in the percentage of time patients spend within the glycemic target range of 0.70-1.80 g/l over this period.

Participants will be required to attend several study visits throughout the trial. The initial visit will serve as a screening to confirm eligibility based on criteria such as age, type 1 diabetes diagnosis, and body mass index (BMI). Following successful screening, participants will be enrolled and begin treatment with semaglutide administered via subcutaneous injection. Follow-up visits will occur at regular intervals to monitor various health parameters, including HbA1c levels, weight, waist circumference, and insulin dosage. Continuous glucose monitoring will be employed to assess glycemic variability and other secondary endpoints. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary and secondary endpoints.

The expected length of participant involvement is 6 months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events or non-compliance with the study protocol. Participants are required to provide written consent and meet specific inclusion criteria, such as being over 18 years of age, having a confirmed diagnosis of type 1 diabetes, and a BMI of 27 kg/m² or higher. The trial aims to provide valuable insights into the management of "double diabetes" and the potential benefits of semaglutide in this patient population.

The clinical trial involves the administration of **semaglutide**, an active substance classified as a protein of other origin. The experimental medication is provided in the form of a solution for injection, specifically in pre-filled pens. Three different dosages of the medication are utilized in the study: Ozempic 0.25 mg, Ozempic 0.5 mg, and Ozempic 1 mg. Each of these formulations is designed for **subcutaneous use**. The maximum daily dose for each formulation is 1 mg, with a total maximum dose of 19 mg over the course of the treatment period. The treatment duration is set for a maximum of 180 days. The administration of the medication is conducted on a weekly basis, ensuring consistent dosing throughout the study period.

In addition to the experimental treatment, participants in the study may receive standard-of-care therapy for type 1 diabetes, which is not specified in the trial data. The study does not include a placebo or comparator treatment. Participant compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol. The trial aims to evaluate the effect of semaglutide on the percentage of time patients with type 1 diabetes and "double diabetes" spend within the glycemic target range over a six-month period.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the percentage of time spent within the glycemic target range of 0.70-1.80 g/l between Day 0 and Day 180. This will be measured using continuous glucose monitoring systems such as Free Style Libre, Guardian, or Dexcom. Secondary endpoints include changes in **HbA1c**, weight, waist circumference, daily insulin dose, and glycemic variability. Glycemic variability will be assessed using the Standard Deviation (SD) and Mean Amplitude of Glycemic Excursions (MAGE) from continuous glucose monitoring data. Additionally, the trial will evaluate interstitial glucose time below 0.7 g/l and 0.54 g/l, as well as the percentage of adverse events in the two groups. Measurements will be collected at multiple timepoints, including baseline (t0), 3 months (t3), and 6 months (t6), to analyze variations in each criterion between these intervals.