Retatrutide Lowers Albuminuria, Glomerular Pressure in Obesity and CKD

Retatrutide, an investigational once-weekly glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptor agonist, reduced albuminuria, intraglomerular pressure, and kidney fat without changing measured glomerular filtration rate (mGFR) in adults with obesity or overweight and chronic kidney disease (CKD), according to 24-week data from the phase 2b TRANSCEND-CKD trial.1

Hiddo J. L. Heerspink, PharmD, PhD, of the University of Groningen, and colleagues presented the findings at ASN Kidney Week 2026 in Denver, Colorado.1

In a prior phase 2 trial in people with obesity or overweight, retatrutide reduced body weight and albuminuria and increased estimated GFR (eGFR).2 Investigators noted eGFR may be influenced by changes in body composition, leaving open whether retatrutide affects mGFR and kidney structure. Retatrutide has since produced weight loss of up to 28.3% at 80 weeks in the phase 3 TRIUMPH-1 trial and A1C reductions of up to 2.0% in TRANSCEND-T2D-1.3,4

Did Retatrutide Change Measured GFR in TRANSCEND-CKD?

TRANSCEND-CKD randomized adults with a BMI of ≥ 27 kg/m² and established CKD, with or without type 2 diabetes, to once-weekly retatrutide or placebo. Eligible participants had a cystatin C–based eGFR of 25 to 75 mL/min/1.73 m². Retatrutide was escalated from 2 mg to 12 mg over 16 weeks and continued at 12 mg through week 24.1

The analysis included 75 participants receiving retatrutide 12 mg and 71 receiving placebo.1 Mean baseline mGFR by iohexol clearance was 53.0 and 52.9 mL/min/1.73 m², respectively, and approximately 30% of participants had a urine albumin-to-creatinine ratio (UACR) of ≥ 30 mg/g.

At week 24, the change in mGFR, the primary end point, did not differ between groups (−1.6 vs −0.2 mL/min/1.73 m²; difference, −1.4; 95% CI, −9.2 to 6.3).¹ In contrast, both creatinine-based and cystatin C–based eGFR increased significantly with retatrutide versus placebo at week 24 (P < .01 for both). Renal blood flow (difference, −7.6 mL/min; 95% CI, −70.2 to 55.1) and filtration fraction were also unchanged.1

How Did Retatrutide Affect Albuminuria, Kidney Hemodynamics, and Kidney Fat?

Among participants with baseline UACR of ≥ 30 mg/g, UACR fell 53.7% with retatrutide versus 8.8% with placebo (difference, −49.2%; 95% CI, −70.6% to −12.3%). The difference reached statistical significance at week 16.1

MRI-derived renal artery resistive index decreased with retatrutide compared with placebo (difference, −0.04; 95% CI, −0.07 to −0.02; P < .001).¹ Estimated intraglomerular pressure declined by 3.2 mm Hg with retatrutide versus 0.4 mm Hg with placebo (difference, −2.8 mm Hg; 95% CI, −5.3 to −0.3). Renal vascular resistance did not differ between groups.1

Retatrutide reduced perirenal fat volume by 16.1% compared with 2.7% with placebo (difference, −13.4%; 95% CI, −18.4% to −8.5%; P < .001) and renal sinus fat by 5.8% vs a 0.7% increase (difference, −6.5%; 95% CI, −11.5% to −1.5%).1

Body weight decreased by 14.0 kg with retatrutide, with no change in the placebo group (difference, −14.0 kg; 95% CI, −16.0 to −12.0). Systolic blood pressure fell 14.0 mm Hg versus 1.0 mm Hg (difference, −13.0 mm Hg; 95% CI, −17.2 to −8.9). Diastolic blood pressure did not differ significantly, and pulse rate increased by 9.0 bpm (95% CI, 5.7–12.3) with retatrutide.1

The investigators concluded the reductions in systolic blood pressure, resistive index, intraglomerular pressure, and UACR suggest a hemodynamic profile supporting a potential long-term kidney-protective effect.1

References

1. Heerspink HJL, Botros FT, Hurt KC, et al. Effects of retatrutide on kidney parameters in participants with obesity or overweight and chronic kidney disease. Poster presented at: ASN Kidney Week 2026; October 21-25, 2026; Denver, CO. Poster TH-PO1238.

2. Heerspink HJL, et al. Kidney Int Rep. 2025;10:1980-1992.

3. Livingston R. TRIUMPH-1: Retatrutide substantially lowers weight, BMI in patients with obesity or overweight. HCPLive. Published June 6, 2026. Accessed October 22, 2026. https://www.hcplive.com/view/triumph-1-retatrutide-substantially-lowers-weight-bmi-in-patients-with-obesity-or-overweight

4. Brooks A. Retatrutide delivers A1C reduction, weight loss in phase 3 TRANSCEND-T2D-1 trial. HCPLive. Published March 19, 2026. Accessed October 22, 2026. https://www.hcplive.com/view/retatrutide-delivers-a1c-reduction-weight-loss-in-phase-3-transcend-t2d-1-trial