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Metformin was both safe and well tolerated in patients with autosomal dominant polycystic kidney disease (ADPKD), the phase II found.

The parallel-group, randomized trial of 97 participants found no significant increase in gastrointestinal symptoms over 24 months, according to Ronald Perrone, MD, of Tufts Medical Center in Boston, and colleagues.

As measured by the Gastrointestinal Symptoms Rating Scale (GSRS), patients on metformin also didn't see any gastrointestinal tolerability issues compared with those on placebo.

"Lactic acidosis and hypoglycemia were not found to be problematic," Perrone said during a presentation of the late-breaking findings at the virtual National Kidney Foundation Spring Clinical Meeting. "However, there was no evidence signal for efficacy to slow progression."

The number of patients able to achieve a maximum dose was not significantly different between the metformin and placebo groups, and during the 2-year trial, 67% of patients on metformin were able to receive the highest possible dosage of 2,000 mg, while 81% of those on placebo achieved this dose (P=0.21), Perrone reported.

Similarly, 43% (21 patients) of those on metformin had to reduce their dose due to intolerability, while 29% (14) of those on placebo opted to reduce their dose.

And the percentage of patients in each group who had at least one serious adverse event, such as hypoglycemia or lactic acidosis, was also essentially the same (8.2% for the metformin group vs 8.3% for the placebo group, P=0.98). A similar percentage in each group also withdrew from the trial (18.4% vs 12.5%, respectively, P=0.80).

However, those on placebo did see a slightly larger decline in estimated glomerular filtration rate (eGFR) throughout the 24-month trial versus those on metformin, for an average greater decline of 2.73 mL/min/1.73 m² (95% CI -1.40 to 6.87; P=0.20), Perrone noted.

Patients on metformin also had a slightly greater average change in annual height-adjusted total kidney volume of 1.68% (95% CI -2.11 to 5.62, P=0.38) more per year, as measured by MRI.

The trial included 97 adult patients ages 18 to 60 with ADPKD and an eGFR over 50 mL/min/1.73 m². There were two clinical study sites: the University of Maryland in Baltimore and Tufts Medical Center.

Perrone explained that because this genetic disease causes cysts in the kidneys, both in vitro and in vivo previous research have shown that metformin may inhibit the growth of kidney cysts, as well as cell proliferation.

Currently the vasopressin antagonist tolvaptan (Samsca) is the only therapy approved for ADPKD, but metformin works "more distally," he explained.

Study participants on metformin were started on a dose of 500 mg once daily, which was then increased to 500 mg twice daily by the second week. By the fourth week, metformin was increased to 1,000 mg in the morning and 500 mg in the evening, which was finally increased by week 6 to 1,000 mg twice daily -- the highest dose.

Tolerability of the medication was assessed using the 15-item GSRS, rate of drug discontinuation -- which was assessed by asking if the participant could tolerate this dose of the study drug for the rest of his or her life -- and what the maximum tolerated dose was at the end of the trial.

"Right now we don't have proven efficacy of metformin," Perrone underscored, as this was only a safety and tolerability study.

"Future trials of metformin in ADPKD are feasible but should be enhanced with prognostic enrichment using genetic or total kidney volume-based imaging classification," he concluded, referencing a current trial underway in Australia -- the -- which is testing the change in eGFR over 24 months in adults with stages 2 to 3a chronic kidney disease who are rapidly progressing ADPKD.

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