Efficacy and Safety Evaluation of Weekly Insulin Icodec Versus Daily Insulin Glargine in Adults with Type 2 Diabetes Transitioning from Basal Insulin

The primary objective of this study is to evaluate the effect on **glycaemic control** of once-weekly **insulin icodec**, switched unit-to-unit from a daily basal insulin, in participants with **Type 2 Diabetes** (T2D) treated with basal insulin. This includes comparing the difference in change from baseline in **HbA1c** between insulin icodec and insulin glargine U100 after 26 weeks of treatment to a non-inferiority margin of 0.3%-point. The clinical relevance of this objective lies in determining whether insulin icodec can provide comparable glycaemic control to the widely used insulin glargine U100, potentially offering a more convenient dosing schedule for patients.

Secondary objectives include:

• Comparing parameters of glycaemic control, patient-reported outcomes, and safety of once-weekly insulin icodec, switched unit-to-unit from a daily basal insulin, compared to once-daily insulin glargine U100. This comparison will be conducted in both treatment arms with or without non-insulin anti-diabetic drugs in participants with T2D treated with basal insulin.

The clinical trial involves a total of **259 participants** diagnosed with **Type 2 Diabetes**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including a diagnosis of Type 2 Diabetes at least 180 days prior to screening and an HbA1c level between 7.0-10.0% at screening. They must have been treated with basal insulin for at least 90 days before screening, with or without stable doses of non-insulin anti-diabetic drugs. The trial includes individuals with a body mass index (BMI) of 40.0 kg/m² or less. The population is considered vulnerable, indicating additional ethical considerations in the study design. Lifestyle factors such as diet and physical activity are not specified, but the inclusion of stable anti-diabetic regimens suggests a focus on maintaining consistent treatment conditions.

The clinical trial is designed to evaluate the efficacy and safety of **insulin icodec**, a once-weekly insulin, compared to the daily administration of **insulin glargine** in adults with **Type 2 Diabetes**. This study employs a randomized, double-blind, controlled trial design to ensure unbiased results. Participants will be randomly assigned to receive either insulin icodec or insulin glargine, with neither the participants nor the investigators aware of the group assignments. The trial is expected to last for 26 weeks, with participant involvement beginning from the screening visit and concluding at the end-of-study visit.

The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as a diagnosis of Type 2 Diabetes at least 180 days prior, an HbA1c level between 7.0-10.0%, and a body mass index (BMI) of ≤40.0 kg/m². Following successful screening, participants will undergo randomization and commence treatment. Regular follow-up visits will be scheduled to monitor glycemic control, safety, and any adverse events. The primary endpoint is the change in HbA1c from baseline to week 26, while secondary endpoints include changes in time in range, treatment satisfaction, and the incidence of hypoglycemic episodes.

The expected length of participant involvement is approximately 26 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The trial aims to demonstrate the non-inferiority of insulin icodec compared to insulin glargine, with a non-inferiority margin set at 0.3%-point for HbA1c change. The study will conclude with an end-of-study visit to assess final outcomes and gather comprehensive data for analysis.

The clinical trial involves the administration of two **insulin** formulations to evaluate their efficacy and safety in adults with Type 2 Diabetes. The experimental medication, **insulin icodec**, is provided as a 700 U/mL solution for injection. It is administered using the PDS290 pen-injector, a disposable, pre-filled, multi-dose device capable of delivering subcutaneous doses of 10 U/increment. The dosing schedule for insulin icodec is once weekly, with a maximum treatment period of 26 weeks. The active substance, insulin icodec, is a protein of non-human origin, and the product is manufactured by Novo Nordisk A/S.

The comparator treatment in this study is **insulin glargine**, marketed as Lantus SoloStar. This formulation is a 100 units/mL solution for injection, provided in a pre-filled pen for subcutaneous administration. Insulin glargine is administered once daily, with the same maximum treatment period of 26 weeks. The active substance, insulin glargine, is also a protein of non-human origin, and the product is manufactured by Sanofi-Aventis Deutschland GmbH. Both treatments are designed to manage blood glucose levels in participants with Type 2 Diabetes, with the primary objective of comparing the change in HbA1c levels from baseline between the two insulin formulations over the course of the study.

The efficacy of the clinical trial will be assessed by evaluating the change in **HbA1c** levels from baseline at week 0 to week 26. This primary endpoint will determine the glycaemic control achieved by participants switching from daily basal insulins to once-weekly insulin icodec, compared to once-daily insulin glargine U100. The trial aims to demonstrate non-inferiority with a margin of 0.3%-point.

Secondary endpoints include changes in the time spent within the glucose range of 3.9–10.0 mmol/L (70–180 mg/dL), total treatment satisfaction as measured by the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs), and the number of severe hypoglycaemic episodes (level 3) and clinically significant hypoglycaemic episodes (level 2) confirmed by blood glucose meters. Additional secondary measures involve the time spent below 3.0 mmol/L (54 mg/dL), changes in time spent above 10.0 mmol/L (180 mg/dL), mean weekly insulin dose, and changes in body weight.

Data collection will occur at specified intervals throughout the 26-week treatment period, with the use of validated scales and laboratory tests to ensure accuracy and reliability. The PDS290 pen-injector, a disposable, pre-filled, multi-dose device, will be utilized for administering insulin icodec subcutaneously, delivering 10 U/increment doses of 700 U/mL insulin icodec.