A Pragmatic Study Evaluating the Efficacy of Once-Weekly Insulin Icodec Versus Daily Basal Insulin Analogues in Insulin-Naïve Adults with Type 2 Diabetes

The primary objective of this study is to evaluate the **effectiveness** of once-weekly insulin icodec compared with once-daily basal insulin analogues in managing glycaemic control in individuals with type 2 diabetes (T2D) who are on non-insulin glucose-lowering medications. This includes assessing the difference in change from baseline in HbA1c levels between the two treatment regimens after 52 weeks, with a non-inferiority margin set at 0.3%. This objective is clinically relevant as it aims to determine if a less frequent dosing schedule can maintain effective glycaemic control, potentially improving patient adherence and quality of life.

Secondary objectives include evaluating the effectiveness of once-weekly insulin icodec versus once-daily basal insulin analogues on:

• Self-reported treatment adherence, satisfaction, and compliance
• Perceived treatment burden
• Safety profile

The clinical trial involves a total of **306 participants** diagnosed with **Type 2 diabetes**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their diagnosis of Type 2 diabetes at least 180 days prior to screening and their current treatment with non-insulin glucose-lowering medications. The trial does not include a vulnerable population. Participants are required to have a recorded HbA1c value of 7% or higher within the last 90 days prior to randomization, indicating a need for intensification with basal insulin. The trial population was chosen to evaluate the effectiveness of once-weekly insulin icodec compared to once-daily basal insulin analogues in real-world clinical practice. Lifestyle considerations such as diet and physical activity were not specified by the sponsor.

The clinical trial is designed to evaluate the effectiveness of once-weekly **insulin icodec** compared to once-daily basal insulin analogues in individuals with type 2 diabetes (T2D) who are on non-insulin glucose-lowering medications. This study is a randomized, double-blind, controlled trial with a primary objective to assess the change in HbA1c levels from baseline to week 52, with a non-inferiority margin of 0.3%. The trial is expected to commence recruitment on August 17, 2025, and conclude by August 4, 2028, with a total duration of 54 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of T2D at least 180 days prior, current treatment with specific non-insulin glucose-lowering medications, and a recorded HbA1c value of 7% or higher within the last 90 days. Following randomization, participants will attend follow-up visits at regular intervals to monitor treatment adherence, glycaemic control, and any adverse events. The end-of-study visit at week 52 will assess the primary and secondary endpoints, including changes in treatment satisfaction and the occurrence of severe hypoglycaemic episodes.

Participant involvement is expected to last for the entire 54-week period unless early termination is warranted due to adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial will utilize subcutaneous administration of the investigational products, ensuring adherence to the protocol's safety and efficacy standards. The study's design and methodology are structured to provide robust data on the comparative effectiveness of the insulin regimens in a real-world clinical setting.

The clinical trial involves the administration of several insulin formulations to evaluate their effectiveness in managing type 2 diabetes. The experimental medication, **insulin icodec**, is provided as a solution for injection in a pre-filled pen, marketed under the name Awiqli 700 units/mL. This formulation is administered subcutaneously once weekly. The pharmaceutical form is a solution for injection, and the maximum treatment period is 54 weeks. The dosing schedule is determined by the investigator, and participant compliance is monitored throughout the study.

In addition to the experimental treatment, the trial includes comparator treatments with other basal insulin analogues. **Insulin degludec** is available as Tresiba, in both 100 units/mL and 200 units/mL concentrations, provided in FlexTouch pre-filled pens or Penfill cartridges. These are administered subcutaneously once daily, with the same maximum treatment period of 54 weeks. The pharmaceutical form is a solution for injection, and dosing is adjusted based on individual patient needs.

Another comparator, **insulin glargine**, is available under the brand names Lantus and Toujeo. Lantus is provided in 100 units/mL concentration in cartridges, pre-filled pens, or vials, while Toujeo is available in 300 units/mL concentration in SoloStar or DoubleStar pre-filled pens. These formulations are also administered subcutaneously once daily, with a maximum treatment period of 54 weeks. The pharmaceutical form is a solution for injection, and dosing is tailored to the patient's requirements.

Lastly, **insulin detemir** is included as a comparator, marketed as Levemir FlexPen or Penfill, with a concentration of 100 units/mL. This formulation is administered subcutaneously once daily, with a maximum treatment period of 54 weeks. The pharmaceutical form is a solution for injection, and dosing is individualized based on patient response.

The efficacy of the clinical trial will be assessed by evaluating the effectiveness of once-weekly **insulin icodec** compared to once-daily basal insulin analogues in participants with type 2 diabetes (T2D) who are on non-insulin glucose-lowering medications. The primary endpoint for efficacy assessment is the change in HbA1c levels from baseline at week 0 to week 52. This will determine the non-inferiority of insulin icodec to a limit of 0.3% in HbA1c change.

Secondary endpoints include several measures to further assess efficacy and treatment impact. These include the Adelphi Adherence Questionnaire (ADAQ©) at week 52, changes in the Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction from baseline to week 52, and the TRIM-D compliance and treatment burden domains at week 52. Additionally, the number of severe hypoglycaemic episodes (level 3) from baseline to week 52, the mean weekly basal insulin dose from week 50 to week 52, and the achievement of individualised HbA1c targets at week 52 will be evaluated.