Evaluation of Efficacy and Safety of Switching from Insulin Glargine 100 U/mL to Insulin Glargine 300 U/mL in Type 2 Diabetes Patients with Renal Impairment

The primary objective of this study is to evaluate the **efficacy** and **safety** of switching treatment from insulin glargine 100 U/ml (Gla-100) to insulin glargine 300 U/ml (Gla-300) using Continuous Glucose Monitoring (CGM) in patients with Type 2 Diabetes Mellitus (T2DM) and renal impairment. This is clinically relevant as it aims to optimize glycemic control and minimize adverse effects in a population with compromised renal function, where treatment adjustments can significantly impact patient outcomes.

Secondary objectives include:

• Determining glycemic variability and control during a 24-hour evaluation period using data from the CGM.
• Assessing the effectiveness of the treatment regimen of Gla-300 versus Gla-100 using data from Electronic Health Records (EHR).
• Evaluating the safety and tolerability profile during a 24-hour evaluation period from CGM data.
• Describing the incidence and severity of documented hypoglycemia events with Gla-300 and pretreatment (Gla-100) using EHR data.
• Describing the incidence of adverse events other than documented hypoglycemias with Gla-300 and pretreatment (Gla-100) using EHR data.
• Describing the characteristics of the patients using EHR data.
• Describing the patient's treatment patterns using EHR data.
• Determining patient satisfaction after the change in their treatment using the "Diabetes Treatment Satisfaction Questionnaire" (DTSQs) and the "Change Diabetes Treatment Satisfaction Questionnaire" (DTSQc).

The clinical trial involves participants diagnosed with **Type 2 Diabetes Mellitus** and renal impairment. The study population includes both male and female subjects aged 18 years and older. Participants are required to have been diagnosed with Type 2 Diabetes Mellitus for at least three years prior to enrollment and must have been treated with insulin glargine 100U/ml for a minimum of four months before joining the study. The trial does not include a vulnerable population. Participants must have an HbA1c level between 7.5% and 9% within three months prior to enrollment and an estimated glomerular filtration rate (eGFR) between 30-60 ml/min at least four weeks before enrollment. The body mass index (BMI) of participants should range from 25 to 40 kg/m². The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified. The selection criteria ensure that participants are capable and willing to comply with the study requirements, including wearing the Freestyle IQ Pro device as per protocol.

The clinical trial is designed to evaluate the **efficacy** and safety of switching from insulin glargine 100 U/ml to insulin glargine 300 U/ml in patients with Type 2 Diabetes Mellitus (T2DM) who have renal impairment. This study employs a randomized, double-blind, controlled methodology to ensure unbiased results. The trial is expected to span approximately 4 months, with participant involvement beginning from the screening visit and concluding at the end-of-study visit. The primary endpoint is the change in the percentage of Time in Range (TIR) from baseline to Month 5, while secondary endpoints include mean glucose profile over 24 hours, percentage of time below and above target glucose range, and changes in HbA1c and fasting plasma glucose levels.

Participants will undergo a sequence of study visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, duration of diabetes diagnosis, current treatment regimen, and renal function. Follow-up visits will be scheduled to monitor the participants' glucose levels and overall health, utilizing Continuous Glucose Monitoring (CGM) technology. The end-of-study visit will assess the final outcomes and any adverse events experienced during the trial. Participants are expected to remain in the study for the full duration unless conditions such as significant adverse events or withdrawal of consent necessitate early termination. The trial aims to provide valuable insights into the management of T2DM in patients with renal impairment, potentially influencing future treatment protocols.

The clinical trial involves the administration of **Insulin Glargine**, a long-acting basal insulin analog, to evaluate its efficacy and safety in patients with Type 2 Diabetes Mellitus (T2DM) and renal impairment. The experimental medication, **Insulin Glargine 300 U/ml** (Gla-300), is provided in a pharmaceutical form identified as PHF00231MIG. The medication is administered via the **subcutaneous route**. The dosing regimen allows for a maximum daily dose of 90 units, with a total maximum dose of 10,800 units over the course of the study. The maximum treatment period is set at four weeks. The trial aims to assess the outcomes of switching from **Insulin Glargine 100 U/ml** (Gla-100) to Gla-300 using Continuous Glucose Monitoring (CGM) to monitor efficacy and safety.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapy as a non-experimental treatment. This includes the administration of **Insulin Glargine 100 U/ml** (Gla-100) prior to switching to the experimental Gla-300. The trial does not utilize a placebo or comparator treatment, focusing instead on the direct comparison of the two formulations of Insulin Glargine. Participant compliance with the dosing schedule is monitored through regular assessments and CGM data to ensure adherence to the treatment protocol.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the change from baseline to Month 5 in the percentage of **Time in Range (TIR)**, which will be measured using Continuous Glucose Monitoring (CGM). Secondary endpoints include the mean glucose profile over 24 hours, percentage coefficient of variation, percentage of time below target glucose range (TBR), percentage of time above target glucose range (TAR), change from baseline to Month 5 in **HbA1c**, change from baseline to Month 5 in fasting plasma glucose (FPG), the number of participants with at least one hypoglycemia event, change from baseline to Month 5 in Diabetes Treatment Satisfaction Questionnaire change version (DTSQc), and the number of participants with adverse events.

Data collection will occur at baseline and at Month 5, with the use of the Freestyle IQ Pro device for CGM to ensure accurate and continuous monitoring of glucose levels. The analysis will focus on comparing the baseline data with the data collected at Month 5 to determine the efficacy of switching from insulin glargine 100 U/ml to insulin glargine 300 U/ml in patients with Type 2 Diabetes Mellitus (T2DM) and renal impairment. The trial is designed to provide comprehensive insights into the efficacy and safety of the treatment switch, with a focus on improving glucose management in the specified patient population.