First trial of tirzepatide in polycystic kidney disease starts enrolling

A phase 2 clinical trial testing tirzepatide in people with autosomal dominant polycystic kidney disease (ADPKD) has begun enrolling patients, according to its registration on ClinicalTrials.gov ^[1]. The study is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and is led by the University of Colorado Denver, with Washington University and Mayo Clinic also involved. It is the first trial to test tirzepatide, the drug sold as Mounjaro and Zepbound, specifically in this kidney disease.

ADPKD is an inherited condition in which fluid-filled cysts grow in the kidneys over time, eventually damaging kidney function. The trial plans to randomize 126 adults with ADPKD and a body mass index of at least 27 to receive either tirzepatide, titrated up to a 5 mg weekly dose, or a placebo, over 12 months ^[1]. People with diabetes or those taking tolvaptan, a drug already approved for ADPKD, are excluded from the study ^[1].

The main outcome researchers will track is the change in height-adjusted total kidney volume, measured by MRI ^[1]. This measurement is the standard way doctors and researchers gauge how fast ADPKD is progressing, since kidney volume tends to grow as cysts multiply and enlarge. Alongside that main measure, the study will also track several biological markers in the blood, including adiponectin, leptin, interleukin-6, TNF-alpha, hs-CRP, and 8-isoprostane ^[1]. These markers are tied to inflammation and metabolism, and measuring them may help explain how or why tirzepatide affects kidney cysts, if it does at all.

The trial's primary completion date is listed as June 2029 ^[1], meaning the main results are likely years away.

Why it matters for patients

For the roughly hundreds of thousands of Americans living with ADPKD, current treatment options are limited. Tolvaptan is approved to slow kidney growth in this disease, but it comes with its own side effects and is not an option for everyone. This trial is testing a different approach: rather than treating ADPKD directly, researchers want to know whether a GLP-1/GIP drug already used for weight management and type 2 diabetes might also slow the disease, possibly through effects on inflammation, metabolism, or body weight itself.

Because the study requires a BMI of at least 27, it is specifically looking at people with ADPKD who also carry excess weight, not the ADPKD population as a whole. That means, even if the trial shows a benefit, the results may not directly apply to leaner ADPKD patients. It is also worth noting that people with diabetes and those on tolvaptan are excluded, so the findings will not immediately clarify how tirzepatide might work alongside standard ADPKD treatment.

It is not yet known whether tirzepatide will show any effect on kidney volume or on the biological markers being tracked. The trial is designed to test that question, not to confirm an established benefit. Patients with ADPKD who are curious about the study, or about whether they might qualify, are not given guidance here; the sources describe the trial's design only, not its results or any recommendations.

What happens next

Enrollment is underway as of the trial's start, with 126 participants targeted for randomization to tirzepatide or placebo over a 12-month treatment period ^[1]. The primary completion date, when the main kidney-volume results are expected to be assessed, is listed as June 2029 ^[1]. Until then, no efficacy or safety results from this trial are available.