Metformin Versus Standard of Care in Patients with Autosomal Dominant Polycystic Kidney Disease - A Randomized Control Trial.

Background: Autosomal dominant kidney disease (ADPKD) is the most common monogenic disorder leading to renal failure with limited therapeutic options. We aimed to assess the efficacy and safety of metformin in nondiabetic ADPKD patients and its role in slowing disease progression.

Materials and methods: We conducted a prospective, randomized controlled, open labelled clinical trial and enrolled 52 nondiabetic adults aged 18-60 years with typical ADPKD, estimated glomerular filtration rate (eGFR) > 45 mL/min/m², and no risk factors of rapid disease progression. Participants were randomized in a 1:1 ratio by a computer-generated random number table into metformin + standard of care group (metformin arm) and standard of care group (Control arm). Primary outcome of the study was to evaluate the effects of metformin versus control arm on the percentage and absolute change in eGFR over a 6-month period.

Results: Mean (SD) age of the cohort was 37.15 (10.16) years with half of them being females. The mean (SD) baseline htTKV and eGFR were 335.67 (153.3) mL/m and 100.23 (25.95) mL/min/m², respectively. Clinical exome sequencing was available in nine (17.3%) patients of which two-thirds had PKD1 mutation. Baseline characteristics were distributed equally across randomized groups. Baseline proteinuria was significantly higher in the metformin arm (p = 0.014). The eGFR difference and percentage change in eGFR was not different between the groups at 6 months (p = 0.53 and 0.48, respectively). There was no statistically significant difference in htTKV and percentage change in htTKV at 6 months between the groups, although an increase in htTKV was numerically smaller in the metformin group (p = 0.769, 0.805). Blood pressure, body weight, body mass index (BMI), and proteinuria also did not differ between the two groups. Only half of the cohort tolerated the maximum dose of metformin. Around two-thirds of patients reported adverse effects, most commonly asthenia.

Conclusion: Metformin appears to be safe and well tolerated in nondiabetic patients with ADPKD.