Cautious metformin use supported with moderately reduced renal function
medwireNews: The risk for acidosis during metformin treatment is no higher than that during alternative treatment among patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) below 30 mL/min per 1.73 m2, study data show.
“These findings support the recent expansion of the eGFR thresholds for metformin use by the FDA, and recommendations from other regulatory bodies, which suggest that metformin can be used when eGFR is 45 to 59 mL/min/1.73 m2 and cautiously when eGFR is 30 to 44 mL/min/1.73 m2,” write Morgan Grams (Johns Hopkins University, Baltimore, Maryland, USA) and co-authors in JAMA Internal Medicine.
However, the researchers note that patients with an eGFR below 30 mL/min per 1.73 m2 had twice the risk for acidosis when using metformin compared with alternative treatments.
The findings are based on a community-based cohort of 75,413 patients (mean age 60 years, 51% women), of whom 34,095 (45.2%) were taking metformin at enrollment and a further 13,781 (18.3%) were prescribed it during the median 5.7-year follow-up period.
Overall, there were 2335 hospitalizations with acidosis: 737 cases occurred during 188,578 person–years of metformin use compared with 1598 cases during 281,536 person–years of alternative treatment use.
After adjustment for change in eGFR stage over time and for potential confounding variables including demographic characteristics, cardiovascular risk factors, glycated hemoglobin, and concomitant medication use, time-dependent metformin use was not significantly associated with incident acidosis overall or in patients with an eGFR of 30–44 or 45–59 mL/min per 1.73 m2.
Of note, the incidence of acidosis increased with decreasing eGFR, regardless of metformin use.
The researchers observed similar results when new metformin users were compared with new sulfonylurea users (n=12,690 overall), when they analyzed propensity score–matched cohorts within each stratum of eGFR, and when insulin users were excluded from the analysis.
Furthermore, the findings were replicated using data from a commercial claims database that included 67,578 new metformin users and 14,439 new sulfonylurea users.
In an accompanying commentary, Chester Good (UPMC Health Plan, Pittsburgh, Pennsylvania, USA) and Leonard Pogach (Department of Veterans Affairs New Jersey Healthcare System, East Orange, USA) say the study “increases our confidence that metformin is safe to use in patients with mild to moderate CKD [chronic kidney disease].”
However, they stress that patients with an eGFR of 30–44 mL/min per 1.73 m2 should have repeated eGFR measurements since a single test has limited accuracy, and that concomitant medication use, social circumstances, and comorbidity can lead to dehydration and worsening renal function.
By Laura Cowen
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