Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study

ABSTRACT Rationale & Objective Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder that leads to kidney failure and has few treatment options. Metformin is well tolerated and safe in other patient populations. The primary objective of this clinical trial was to determine the safety and tolerability of metformin in patients with ADPKD and without diabetes mellitus. Study Design Prospective, randomized, controlled, double-blind clinical trial. Setting & Participants N=51 adults 30-60 years of age with ADPKD, without diabetes, and an estimated glomerular filtration rate (eGFR) 50-80 mL/min/1.73 m2. Intervention Metformin (maximum dose 2,000 mg/day) or placebo for 12 months. Outcomes Co-primary endpoints were the percentage of participants in each group prescribed at the end of the 12-month period: (a) the full randomized dose, and (b) at least 50% of the randomized dose. Secondary and exploratory outcomes were the effect of metformin compared to placebo on (a) percent change in TKV referenced to height (htTKV in mL/m) and (b) change in eGFR over a 12-month period. Results Mean age was 48 ± 8 years and eGFR was 70 ± 14 mL/min/1.73m 2 . The metformin group had no cases of lactic acidosis and there was one episode of mild hypoglycemia in each group. Participants in the metformin group reported more adverse symptoms, mostly related to gastrointestinal symptoms. 11 of 22 (50%) of metformin-treated participants completed the treatment phase on the full dose compared to 23 of 23 (100%) in the placebo group. 82% of participants on metformin tolerated at least 50% of the dose, compared to 100% in the placebo group. In exploratory analyses, changes in height-adjusted total kidney volume or eGFR were not significantly different between groups. Limitations Short study duration. Conclusions 50% or more of the maximal metformin dose was safe and well tolerated over 12 months in patients with ADPKD. Safety of other preparations of metformin as well as its efficacy should be tested in future clinical trials.