Evaluation of Retatrutide (LY3437943) on Renal Function in Overweight or Obese Patients with Chronic Kidney Disease with or without Type 2 Diabetes

The primary objective of this study is to evaluate the effect of **Retatrutide** (LY3437943) compared to placebo on the change in measured Glomerular Filtration Rate (**mGFR**) from baseline to Week 24 in participants with overweight or obesity and chronic kidney disease, with or without type 2 diabetes. This is clinically relevant as it aims to assess the potential renal benefits of Retatrutide, which could inform treatment strategies for managing chronic kidney disease in this patient population.

The clinical trial involves a total of **102 participants** who are diagnosed with **Chronic Kidney Disease (CKD)**, with or without **Type 2 Diabetes**, and are either **overweight** or have **obesity**. The study population includes both male and female subjects, with an age range that spans from **18 to 65 years**. Participants were selected based on specific criteria, including being overweight and having CKD, with or without Type 2 Diabetes, managed through diet and exercise or stable doses of up to three oral diabetic medications. The trial does not exclude based on gender, and it includes a vulnerable population. Lifestyle considerations such as diet and physical activity are relevant, given the inclusion of individuals with Type 2 Diabetes managed by these means. The selection process ensures a representative sample of the target population, focusing on those with the specified medical conditions and lifestyle factors.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the effect of **Retatrutide** (LY3437943) on renal function in participants with overweight or obesity and chronic kidney disease, with or without type 2 diabetes. The trial aims to compare the effect of LY3437943 to placebo on the change in glomerular filtration rate (GFR) from baseline to Week 24, using **iohexol** clearance as the primary endpoint. The study is expected to commence recruitment on November 15, 2023, and conclude by November 25, 2025, with an estimated duration of 24 weeks for each participant's involvement.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as being overweight, having chronic kidney disease, and either having no type 2 diabetes or being treated with diet and exercise only. Following successful screening, participants will be randomized to receive either LY3437943 or a matching placebo, both administered as a solution for injection. The trial includes regular follow-up visits to monitor safety, efficacy, and adherence to the treatment regimen. The end-of-study visit will evaluate the primary and any secondary endpoints, ensuring comprehensive data collection.

Participant involvement is expected to last for the full 24-week duration unless conditions necessitate early termination. Such conditions may include adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial is conducted under strict regulatory guidelines to ensure participant safety and data integrity, with all procedures adhering to ethical standards for clinical research.

The clinical trial involves the administration of **IOHEXOL**, a chemical substance used as an auxiliary treatment. IOHEXOL is provided in the pharmaceutical form of a solution for injection. The maximum daily dose is 3235 mg, with a total maximum dose of 9705 mg over a treatment period of up to 3 days. The administration route is via injection, and the dosing schedule is determined based on the specific requirements of the trial protocol. Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence to the treatment plan.

The experimental medication in this trial is **Retatrutide**, also known by its sponsor product code LY3437943. Retatrutide is a protein-based substance formulated as a solution for injection. The trial does not specify a maximum daily or total dose for Retatrutide, indicating that dosing is likely tailored to individual participant needs or study objectives. The treatment period for Retatrutide is set for 1 week, and the administration is conducted through injection. Compliance with the dosing schedule is closely monitored to maintain the integrity of the trial data.

A **placebo** is also utilized in this study to match LY3437943, serving as a comparator to evaluate the efficacy of Retatrutide. The placebo is designed to mimic the appearance and administration route of the experimental drug, ensuring blinding in the trial. The placebo does not contain any active substance and is administered according to the same schedule as Retatrutide. Monitoring of participant adherence to the placebo regimen is conducted to ensure consistency and reliability of the trial outcomes.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the change in **glomerular filtration rate (GFR)** measured in mL/min/m² using iohexol clearance. This assessment will be conducted from baseline to Week 24. The trial aims to compare the effect of the investigational product, LY3437943, to a placebo in participants with overweight or obesity and chronic kidney disease, with or without type 2 diabetes. The measurement of GFR using iohexol clearance is a validated method for assessing renal function, providing a reliable indicator of the treatment's efficacy. Data collection will occur at specified timepoints, ensuring consistent and accurate evaluation of the primary endpoint throughout the study duration.