A Study of Tirzepatide (LY3298176) 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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We are doing this study to learn more about how tirzepatide may help fight chronic kidney disease in people with obesity with or without type 2 diabetes (T2D). The study will last about 56 weeks and include up to 12 visits.

Official Title
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Tirzepatide Study of Renal Function in People With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes: Focus on Kidney Hypoxia in Relation to Fatty Kidney Disease Using Multiparametric Magnetic Resonance Imaging

Conditions
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Overweight, Obesity, Chronic Kidney Disease, Type 2 Diabetes, T2D

Intervention / Treatment
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* Drug: Tirzepatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants with or without diabetes: Have a Body Mass Index (BMI) ≥27 kilogram/square meter (kg/m²) at screening Diagnosed with chronic kidney disease (CKD) Has an estimated glomerular filtration rate (eGFR) ≥30 to ≤60 ml/min/1.73 m² or eGFR ≥30 to ≤75 ml/min/1.73 m² if urine albumin-to-creatinine ratio (UACR) >30 milligram/gram (mg/g) Have been receiving an angiotensin-converting enzyme (ACE) or angiotensin II receptor blockers (ARB) that is considered the maximal appropriate dose by the investigator for treatment of chronic kidney disease or hypertension (unless the participant has low blood pressure or hypotension) Participants without diabetes: Have Hemoglobin A1c (HbA1c) <6.5% at screening Participants with Type 2 diabetes: Have been diagnosed at least 180 days prior to screening Have HbA1c ≥7.0% to ≤10.5% at screening Exclusion Criteria: All participants: Have a self-reported change in body weight >5 kilogram (kg) within 90 days prior to screening. Have a prior or planned surgical treatment for obesity Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 180 days Have eGFR <30 mL/min/1.73m² calculated by using creatinine-based chronic kidney disease epidemiology collaboration (CKD-EPI) equations, as determined by central laboratory at screening. Have a history of unstable or rapidly progressing renal disease according to investigator judgment Have a known clinically significant gastric emptying abnormality (for example, severe diabetic gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect GI motility) Have had a history of chronic or acute pancreatitis Participants with T2D: Have history of proliferative diabetic retinopathy or diabetic macular edema or non-proliferative diabetic retinopathy that requires acute treatment. Have been diagnosed with type 1 diabetes (T1D) or have history of ketoacidosis or hyperosmolar state/coma

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: Tirzepatide<br>Tirzepatide administered subcutaneously (SC) | Drug: Tirzepatide<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Placebo administered SC | 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 Kidney Oxygenation in Participants With or Without T2D | Blood oxygenation-level dependent magnetic resonance imaging (BOLD MRI) | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Kidney Oxygenation in Participants with T2D (BOLD MRI) |  | Baseline, Week 52 | 
| Change from Baseline in Kidney Oxygenation in Participants without T2D (BOLD MRI) |  | Baseline, Week 52 | 
| Percent Change from Baseline in Body Weight |  | Baseline, Week 52 | 
| Percent Change from Baseline in Renal Sinus Fat Content (MRI) |  | Baseline, Week 52 | 
| Percent Change from Baseline in Renal Fat Content (MRI Proton Density Fat Fraction) |  | Baseline, Week 52 | 
| Percent Change from Baseline in Renal Blood Flow (Phase-Contrast MRI) |  | Baseline, Week 52 | 
| Change from Baseline in Apparent Diffusion Coefficient (ADC) MRI |  | Baseline, Week 52 | 
| Change from Baseline in Glomerular Filtration Rate (GFR) Iohexol Clearance in Milliliter/Minute/Square Meter (ml/min/m²) |  | Baseline, Week 52 | 
| Change from Baseline in 24-hour Urinary Albumin Excretion (UAE) in Milligram/24 Hours (mg/24h) |  | Baseline, Week 52 | 
| Percent Change from Baseline in Urine Albumin-to-Creatine Ratio (UACR) |  | Baseline, Week 52 |