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Metformin safe for most patients with type 2 diabetes and CKD

By Rebecca Jenkins
Metformin is safe to use in most patients with type 2 diabetes and chronic kidney disease (CKD), a large US study has found.

Analysing data from two large and diverse cohorts, researchers found metformin was not associated with incident acidosis in patients with diabetes with an estimated glomerular filtration rate (eGFR) of at least 30mL/min/1.73 m2.

In their primary cohort, a data set of 75,413 patients with diabetes from a large US health maintenance organisation, risk of acidosis only increased when eGFR was less than 30mL/min/1.73 m2, researchers wrote in JAMA Internal Medicine.

Results were consistent even after accounting for changes in eGFR stage over time and controlling for several confounders such as use of multiple medications, cardiovascular risk factors and age.

‘This was true in adjusted, active comparator, and propensity score-matched analyses, and in a replication cohort of 82,017 patients from a nationwide database of health care claims,’ researchers said.

The findings supported the recent US Food and Drug Administration (FDA) decision to expand eGFR thresholds for metformin use and recommendations from other regulatory bodies suggesting metformin could be used when eGFR was 45 to 59 mL/min/1.73 m2 and cautiously when eGFR was 30 to 44mL/min/1.73 m2.

Associate Professor Neale Cohen, Director of Clinical Diabetes at the Baker Heart and Diabetes Institute in Melbourne, said the findings supported accepted practice in Australia to use metformin down to an eGFR of 30mL/min/1.73 m2.

‘There is ongoing debate about metformin and renal impairment in particular, and I think we have relaxed our ideas about metformin in the last 10 years or so,’ he told Endocrinology Today.

‘It’s very reassuring that [in this study] there is just no signal for any increased incidence of acidosis at this stage of kidney disease.’

Questions remained, however, around treatment for patients with eGFR less than 30mL/min/1.73 m2, Professor Cohen said, noting this group was in the ‘land of limited opportunities’ when it came to therapies.

Dipeptidyl peptidase-4 inhibitors were extremely safe but had to be used in combination with metformin under PBS restrictions, he said.

Further trial results on the glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors in this patient group were hotly anticipated, with these antidiabetic agents seeming to have cardioprotective and renoprotective effects.
JAMA Intern Med 2018; doi: 10.1001/jamainternmed.2018.0292.