A single-arm pilot study of metformin in patients with autosomal dominant polycystic kidney disease

BACKGROUND: Metformin has shown promising results regarding cystogenesis inhibition in preclinical studies with autosomal dominant polycystic kidney disease (ADPKD) models. We designed a prospective, preliminary, single-arm study to evaluate the tolerability, safety and the effect of Metformin on kidney function and body mass index (BMI) in Romanian patients with ADPKD. METHODS: We enrolled 34 adult patients with ADPKD, chronic kidney disease (CKD) stages 1–5 not on dialysis and without diabetes mellitus. The primary endpoint was to assess the tolerability and safety of Metformin. The secondary endpoints evaluated changes in estimated glomerular filtration rate (eGFR), body mass index (BMI) and renal replacement therapy (RRT) necessity. Patients received an initial dose of Metformin of 500 mg/day within the first month that was increased to 1000 mg/day thereafter according to tolerability. Change in eGFR and BMI was expressed as mean difference with the corresponding 95% confidence intervals and as a percentage. For the primary endpoint, we included all 34 enrolled patients. To assess the secondary endpoint, intention-to-treat (ITT) and per-protocol (PP) analysis was performed. RESULTS: Sixteen patients out of 34 completed the follow-up period at 24 months. Eighteen patients developed adverse events and 63.6% of these events were gastrointestinal related. Nausea was the most common adverse event (17.6%). Two patients (5.8%) permanently discontinued medication due to adverse events. We recorded no case of hypoglycemia, lactic acidosis or death. Mean eGFR changed by − 1.57 ml/min/1.73m(2) (95%CI:-22.28 to 19.14, P = 0.87) in ITT and by − 4.57 ml/min/1.73m(2) (95%CI:-28.03 to 18.89, P = 0.69) in PP population. Mean BMI change was − 1.10 kg/m(2) (95%CI:-3.22 to 1.02, P = 0.30) in ITT population and − 0.80 kg/m(2) (95%CI:-3.27 to 1.67, P = 0.51) in PP analysis. Three patients (8.8%) needed RRT. CONCLUSIONS: Metformin was well tolerated, had a good safety profile even in ADPKD patients with advanced CKD and it was not associated with change in eGFR or BMI across the follow-up period. TRIAL REGISTRATION: The study was retrospectively registered on https://www.isrctn.com (number ISRCTN 93749377); date registered: 02/25/2019.