Metformin, Potential Treatment for ADPKD, Currently Undergoing Investigation in Long-Term Efficacy Trial

Metformin could positively impact the well-being of patients with autosomal dominant polycystic kidney disease (ADPKD) if proven effective, wrote authors of a study published in Trials. If metformin demonstrates long-term efficacy, it can become a more affordable and accessible treatment option for patients with ADPKD.¹

Globally, ADPKD is the fourth most common reason for dialysis initiation, with an estimated prevalence of 1 in 1000 in the general population. Symptoms consist of exponential cyst growth that damages and distorts normal kidney tissue, resulting in enlarged, painful kidneys and can eventually culminate into progressive chronic kidney disease (CKD). Approximately 35.5 million adults live with CKD, and an estimated 1 in 7 US individuals have the disease. Progression of the disease can lead to end-stage renal disease (ESRD) and kidney failure. Patients with CKD can benefit from specialized care from a nephrologist and additional education, and pharmacists are crucial in leading medication management, patient education, and collaboration in the treatment of CKD.^1,2

There is a significant need for new condition-specific therapies to slow the rate of cyst growth and the progression of kidney function decline to improve patient outcomes alongside reducing health care spending. Metformin, an oral glucose-lowering agent prescribed to 150 million people globally for type 2 diabetes mellitus (T2DM), has a growing body of preliminary evidence that suggests possible benefits in patients with ADPKD. Investigators conducted an international, prospective, blinded, parallel-group, randomized controlled phase 3 trial, IMPEDE-PKD (NCT04939935), to assess the long-term efficacy and safety of metformin extended release when slowing the rate of kidney function decline, reducing morbidity and mortality, and improving quality of life in patients with ADPKD.^1,3

For this trial, 1174 adult patients ages 18 to 70 years with an estimated glomerular filtration rate (eGFR) between 38 and 90 mL/min/1.73 m² were enrolled. Patients were randomly assigned to receive either extended-release metformin (500–2000 mg per day depending on patient’s level of tolerance and eGFR) or placebo, both of which are administered alongside standard of care over a 2-year duration. The primary end point is the change in eGFR, and secondary end points including severity of change in eGFR, annualized slope of eGFR, composite outcome, kidney failure, ADPKD-related pain, and changes in urine albumin to creatinine ratio, among others.^1,3

Although long-term efficacy is still undergoing investigation, prior research shows that metformin has positive benefits in the treatment of patients with ADPKD. One study from 2021 demonstrated that the annual change in eGFR was about –1.71 mL/min/1.73m² for those treated with metformin compared with –3.07 mL/min/1.73m² in those treated with placebo (mean difference: 1.37 [−0.70, 3.44] ml/min/1.73m²). Additionally, mean annual percent changes in height-adjusted total kidney volume were about 3.87% and 2.16% per year in these respective groups (mean difference: 1.68% [−2.11, 5.62]).⁴

Existing treatment, according to the authors of the 2025 study, consists of the disease-modifying therapy tolvaptan (Jynarque; Otsuka Pharmaceutical Co.), a vasopressin receptor agonist. Its widespread use is limited by adverse effects, high cost, and restricted availability; therefore, treatments that are affordable and widely available.¹

“Based on pilot and experimental data, metformin warrants evaluation as an effective, safe and affordable therapy to slow the progression of kidney function decline in ADPKD, possibly either alone or in addition to tolvaptan therapy,” they concluded. “Given the current lack of options for slowing ADPKD progression, this would be a welcome addition to treatment regimens.”¹

REFERENCES

1. Pierre KS, El-Damanawi R, Johnson DW, et al. Implementation of Metformin Therapy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD): study protocol for a phase III, multi-centre, randomized, placebo-controlled trial evaluating the long-term efficacy of metformin in slowing the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease. Trials. 26, 302 (2025). doi:10.1186/s13063-025-09010-6

2. Pervanas H. Patient Perceptions Support Co-Management of Chronic Kidney Disease. Pharmacy Times. August 14, 2025. Accessed August 25, 2025. https://www.pharmacytimes.com/view/patient-perceptions-support-co-management-of-chronic-kidney-disease

3. Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD). ClinicalTrials.gov identifier: NCT04939935. Updated July 1, 2025. Accessed August 25, 2025. https://www.clinicaltrials.gov/study/NCT04939935

4. Perrone RD, Abebe KZ, Watnick TJ, et al. Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD). Kidney Int. 2021;100(3):684-696. doi:10.1016/j.kint.2021.06.013