TAME PKD Results: Phase 2 Trial of Metformin in ADPKD

Spring Clinical Meetings 2021

Growth of kidney cysts in autosomal dominant polycystic kidney disease (ADPKD) was inhibited with metformin in both in vitro and in vivo ADPKD models. Results of TAME PKD, a phase 2, parallel-group, randomized, double-blind, placebo-controlled trial, were reported by Ronald Perrone, MD, during a virtual poster session at the NKF 2021 Spring Clinical Meetings. The poster was titled A Randomized Trial of Administration of Metformin in PKD (TAME PKD).

The primary outcomes of interest in TAME PKD were the tolerability, safety, and preliminary efficacy of metformin in ADPKD.

TAME PKD enrolled 97 participants from June 2016 to December 2018. Inclusion criteria were age 18 to 60 years, and estimated glomerular filtration rate (eGFR) >50 mL/min/1.73 m².

Medication tolerability was defined by (1) gastrointestinal symptoms assessed using the Gastrointestinal Symptoms Rating Scale (GSRS, range 1-7); (2) response to “Can you tolerate this dose of the study drug for the rest of your life?”; and (3) maximally tolerated dose at 24 months. Safety was defined by adverse events and serious adverse events, including prospectively defined hypoglycemia and lactic acidosis. The primary safety outcome was based on the proportion of study participants who experienced at least one serious adverse event during 24 months of study follow-up.

At baseline, the GSRS was low in both the metformin group and the placebo group; there was no significant change in GSRS over time. The highest achieved dose of 2000 mg was similar between the two groups: 67% in the Metformin group and 81% in the placebo group.

Dose was reduced in 23 participants in the metformin group (43%) due to inability to tolerate versus 14 participants in the placebo group (29%). Proportions of participants who withdrew from the study were similar in the two groups. The proportion of participants experiencing at least one serious adverse event was also similar between the groups.

Mean annual percent change in height adjusted total kidney volume was 1.68% more in the metformin group compared with the placebo group. The 24-month decline in eGFR was 2.73 mL/min/1.73 m² greater in the placebo group than in the metformin group.

In conclusion, the researchers said, “The TAME PKD study has demonstrated tolerability and safety of metformin in ADPKD. Demonstration of efficacy to slow progression will require a larger study enriched in participants at risk of rapid progression.”

Source: Perrone R, Abebe K, Watnick T, et al. A randomized trial of administration of metformin in PKD (TAME PKD). Abstract of a poster presented at the National Kidney Foundation virtual 2021 Spring Clinical Meetings (Abstract #331), April 9, 2021.