A Study of Retatrutide (LY3437943) on Renal Function in Participants With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes

Study Overview
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Brief Summary
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The main purpose of this study is to investigate the effect of retatrutide on renal function in participants with overweight or obesity and chronic kidney disease (CKD), with or without Type 2 Diabetes (T2D). The study will lasts around 31 weeks.

Official Title
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A Phase 2b, Double-Blind Study to Investigate the Effect of LY3437943 on Renal Function in Participants With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes

Conditions
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Overweight or Obesity, CKD, Type 2 Diabetes

Intervention / Treatment
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* Drug: LY3437943
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index (BMI) ≥27 kilogram/square meter (kg/m²) Have either no T2D with an HbA1c <6.5% (<48 mmol/mol) or have T2D with an HbA1c 10.5% (≤91 mmol/mol), and treated with diet and exercise only with stable doses of up to 3 oral antihyperglycemic medications, with or without basal insulin. Are on stable treatment, for at least 90 days before screening. Have been diagnosed with chronic kidney disease (CKD). Exclusion Criteria: Have a self-reported change in body weight >5 kilogram (kg) (11 pounds) within 90 days before screening. Have used in 90 days before the screening any of the following antihyperglycemic class: Dipeptidyl Peptidase IV (DPP4) inhibitors, amylin analogs, glucagon-like peptide-RA (GLP-RA), gastric inhibitory polypeptide (GIP)/GIP-1 RA, and short acting or rapid acting of U500 Insulins Have a prior or planned surgical treatment for obesity Have Type 1 Diabetes (T1D) Have acute or chronic hepatitis Have a history of malignant disease within 5 years before screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3437943<br>Participants will receive multiple doses of LY3437943 subcutaneously (SC) | Drug: LY3437943<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Participants will receive LY3437943 | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Glomerular Filtration Rate (GFR) | The GFR in milliliter/minute/square meter (mL/min/m²) using iohexol clearance (mGFR-measured glomerular filtration rate) | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Urine Albumin-to-Creatinine Ratio (UACR) |  | Baseline, Week 24 | 
| Change from Baseline in Creatinine-Corrected Fractional Urinary Sodium Excretion (FENa) |  | Baseline, Week 24 | 
| Change from Baseline in Filtration Fraction Estimated from Measured Glomerular Filtration Rate (mGFR) |  | Baseline, Week 24 | 
| Change from Baseline Magnetic Resonance Imaging (MRI) | MRI assessed renal mean arterial flow, corrected by hematocrit. | Baseline, Week 24 | 
| Change from Baseline in in Mean Arterial Flow (MAF) |  | Baseline, Week 24 | 
| Change from Baseline in Renal Artery Resistive Index (RARI) |  | Baseline, Week 24 | 
| Change from Baseline in Renal Blood Flow Velocity Peak Systolic Velocity (PSV) and End-diastolic Velocity (ESV) |  | Baseline, Week 24 | 
| Change from Baseline in Global Renal Perfusion (MRI) |  | Baseline, Week 24 | 
| Change from Baseline in Total Renal Parenchyma Volume (MRI) |  | Baseline, Week 24 | 
| Change from Baseline in Renal Cortex Volume (MRI) |  | Baseline, Week 24 | 
| Change from Baseline in Renal Cortex T1 (ms) (MRI) |  | Baseline, Week 24 | 
| Change from Baseline in Medulla T1 (ms) (MRI) |  | Baseline, Week 24 | 
| Change from Baseline in Renal Cortex R2 (BOLD MRI) |  | Baseline, Week 24 | 
| Change from Baseline in Medulla R2 |  | Baseline, Week 24 | 
| Change from Baseline in Body Weight |  | Baseline, Week 24 | 
| Change from Baseline in 24-hr Urinary Albumin Excretion (UAE) |  | Baseline, Week 24 | 
| Change from Baseline in Change in 24-hour (hr) Urinary Electrolytes (mg/24hr) |  | Baseline, Week 24 |