Rationale, design and baseline characteristics of the TRANSCEND-CKD trial of retatrutide in patients with chronic kidney disease.
TRANSCEND-CKD (NCT05936151) is a double-blind, placebo-controlled Phase 2b mechanistic trial evaluating retatrutide — a triple agonist of the GIP, GLP-1, and glucagon receptors — in adults with overweight or obesity and chronic kidney disease (CKD). The publication describes the trial's rationale, design, and baseline characteristics of the 146 randomized participants (out of 367 screened). Participants had a mean age of 65.1 years, mean BMI of 35.7 kg/m², and mean measured GFR of 49.3 mL/min/1.73 m² (eGFR range 25–75). Roughly 38% had type 2 diabetes. Participants were randomized 1:1 to once-weekly retatrutide (maximum tolerated dose up to 12 mg) or matched placebo. The primary endpoint is change in measured GFR via iohexol clearance at 24 weeks; secondary endpoints include MRI-assessed kidney hemodynamics, volumes, and perirenal/renal sinus fat. The study is explicitly designed as a mechanistic precursor to the larger cardio-kidney outcomes trial TRIUMPH-Outcomes. Because this paper reports only design and baseline data — with no efficacy or safety outcomes yet — no conclusions about retatrutide's effects on kidney function can be drawn from it.
Why this grade: This publication reports only trial design and baseline characteristics of an ongoing RCT; no outcome data have been presented, making it insufficient to grade evidence for efficacy or safety claims.
Background and hypothesis Retatrutide is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and glucagon receptors that reduced weight and hemoglobin A1c (HbA1c) in individuals with obesity and type 2 diabetes (T2D). Retatrutide may also address key chronic kidney disease (CKD)-related pathophysiological pathways. Mechanism-of-action studies are needed to understand its effects on kidney function. Methods TRANSCEND-CKD is a double-blind, placebo-controlled, Phase 2b mechanistic study evaluating the efficacy of retatrutide in adults with overweight/obesity and CKD [estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2], with and without T2D. Participants were randomized 1:1 to once-weekly retatrutide maximum tolerated dose up to 12 mg or matched placebo. The primary objective is to evaluate the effect of retatrutide versus placebo on change in measured glomerular filtration rate (mGFR) by iohexol clearance from baseline to Week 24. Additional objectives include changes in magnetic resonance imaging-assessed kidney hemodynamic and volumetric measurements, including perirenal and renal sinus fat. Results Of 367 participants screened, 146 were randomized to study interventions. The mean age was 65.1 years [standard deviation (SD) 10.6], 45.2% were female and 69.9% were White. The mean weight was 101.1 kg (SD 20.6) and body mass index 35.7 kg/m2 (SD 6.1). Participants with T2D (37.7%) had a mean HbA1c of 7.1% (SD 1.1%), while HbA1c was 5.7% (SD 0.3%) in participants without T2D. The mean mGFR was 49.3 mL/min/1.73 m2 (SD 19.0), cystatin C-based eGFR was 49.6 mL/min/1.73 m2 (SD 13.2) and creatinine-based eGFR was 64.2 mL/min/1.73 m2 (SD 17.8). The median baseline urine albumin-to-creatinine ratio was 14.0 mg/g (interquartile range 6.0-69.0). A total of 21.8% of participants were treated with sodium-glucose cotransporter-2 inhibitors at baseline. Conclusions TRANSCEND-CKD is designed to provide mechanistic insights on the effects of retatrutide on kidney function and structure, and to inform clinical findings in the ongoing cardio-kidney outcome trial TRIUMPH-Outcomes (NCT06383390). Clinical trial registration number NCT05936151.
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