Phase 2 Chronic Kidney Disease Trial (NCT05936151)

Study Overview

The Phase 2 CKD trial extends retatrutide’s study beyond obesity and type 2 diabetes into kidney disease. It followed kidney-related signals in post hoc analyses of the Phase 2 trials, including lower albuminuria at the higher doses.

Scientific Rationale

Obesity-CKD Connection

Obesity is an independent risk factor for chronic kidney disease progression. Excess adiposity contributes to:

• Glomerular hyperfiltration and subsequent nephron damage
• Inflammatory cytokine release from visceral adipose tissue
• Activation of the renin-angiotensin-aldosterone system (RAAS)
• Insulin resistance and metabolic stress on renal tubular cells

Potential Direct Renal Effects

The glucagon receptor component of retatrutide’s triple agonism may provide kidney benefits beyond weight loss:

• GLP-1 receptor agonism has shown kidney-protective effects in the FLOW trial with semaglutide
• Glucagon receptor activation may reduce renal inflammation and fibrosis
• GIP receptor signaling has emerging evidence for anti-inflammatory effects in the kidney

Phase 2 Obesity Trial Signals

A post hoc analysis of the Phase 2 obesity and type 2 diabetes trials (Heerspink et al., Kidney International Reports, 2025), in participants with eGFR of 45 or higher, found:

• In type 2 diabetes, 12 mg lowered urine albumin-to-creatinine ratio (UACR) by 37.0% versus placebo at 36 weeks, with no change in eGFR
• In obesity, 8 mg and 12 mg lowered UACR by 28.0% and 31.5% versus placebo at 48 weeks and raised creatinine-based eGFR by 5.3 and 8.5 mL/min/1.73m²
• Most participants had normal albumin levels, so the absolute UACR change was small

TRANSCEND-CKD was designed to test these signals with measured kidney function in people who already have CKD.

Study Design

Population

Adults aged 18 or older with:

• Chronic kidney disease with eGFR 25-75 mL/min/1.73m²
• BMI ≥27 kg/m²
• With or without type 2 diabetes (if present, HbA1c 9.5% or lower)

Participants were randomized 1:1 to once-weekly retatrutide at the maximum tolerated dose up to 12 mg, or placebo. At baseline (146 randomized), mean age was 65 years, mean BMI 35.7 kg/m², mean measured GFR 49.3 mL/min/1.73m², and 38% had type 2 diabetes.

Endpoints

Primary endpoint:

• Change in measured GFR (iohexol clearance) from baseline to week 24

Secondary endpoints (all at week 24) include:

• Change in UACR and 24-hour urinary albumin excretion
• MRI measures of kidney blood flow, perfusion, volume and fat around the kidney
• Body weight change

Status

ClinicalTrials.gov lists NCT05936151 as a Phase 2b trial that enrolled 146 participants, started in July 2023 and completed in October 2025. We have not found published results as of October 31, 2026.

Significance

If successful, this trial could make retatrutide a treatment option for people with CKD and obesity, a growing group with few treatment options. The results may also show how triple receptor agonism affects the kidneys beyond the effect of weight loss.

Other Drugs Tested in Kidney Disease

Semaglutide demonstrated significant kidney protection in the FLOW trial (2024), leading to an expanded indication for CKD. Retatrutide’s added glucagon and GIP receptor activity could give different or greater kidney benefits than single GLP-1 agonists.