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Metformin safe in patients with mild, moderate chronic kidney disease

Use of metformin did not increase incident lactic acidosis in patients with estimated glomerular filtration rate greater than 30 mL/min/1.73 m², according to a new study published in JAMA Internal Medicine.

“Approximately 1 million patients in the United States with type 2 diabetes mellitus and mild-to-moderate kidney disease do not receive guideline-directed therapy with metformin,” Benjamin Lazarus, MBBS, MPH, from Johns Hopkins Bloomberg School of Public Health, and colleagues wrote. “This may reflect uncertainty regarding the risk of acidosis in patients with chronic kidney disease.”

Lazarus and colleagues analyzed data from two large retrospective studies to investigate the association between metformin use and lactic acidosis among patients with chronic kidney disease. The primary cohort included 75,413 patients with diabetes (mean age, 60.4 years; 51% women). The researchers replicated the results in a second cohort of 67,578 new metformin users and 14,439 new sulfonylurea users.

Nearly half (45%; n = 34,095) of participants received metformin at baseline and 13,781 received metformin at follow-up. During a median follow-up of 5.7 years, 2,335 hospitalizations for acidosis occurred.

Time-dependent metformin use was not linked to incident acidosis (adjusted HR = 0.98; 95% CI, 0.89-1.08) compared with nonuse. There was not a statistically significant risk of acidosis associated with metformin at estimated glomerular filtration rate (eGFR) between 45 and 59 mL/min/1.73 m² (aHR = 1.16; 95% CI, 0.95-1.41) and eGFR between 30 and 44 mL/min/1.73 m² (aHR = 1.09; 95% CI, 0.83-1.44).

At eGFR less than 30 mL/min/1.73 m², metformin use increased the risk for acidosis (aHR = 2.07; 95% CI, 1.33-3.22). These results were stable when comparing new metformin users with new sulfonylurea users and when excluding baseline insulin users.

“Our results support cautious use of metformin in patients with type 2 [diabetes] and eGFR of at least 30 mL/min/1.73 m²,” Lazarus and colleagues concluded.

In an accompanying editorial, Chester B. Good, MD, MPH, from the University of Pittsburgh Medical Center Health Plan, and Leonard M. Pogach, MD, MBA, from the Department of Veterans Affairs New Jersey Healthcare System, wrote that the findings by Lazarus and colleagues affirm that metformin is safe for patients with mild to moderate chronic kidney disease.

“We believe that when presented with a balanced risk-benefit discussion of all three agents, many if not most patients will choose metformin as the first-line drug in the setting of [chronic kidney disease],” they wrote. “However, there is clearly a role for the newer agents, particularly for those patients who need more than one agent to treat their diabetes, or for those who are unable to tolerate metformin, or who are no longer appropriate candidates for the medication.”

“The challenge is for clinicians to present clear information to guide patient decisions, based on each patient’s clinical circumstances and preferences,” they added. – by Alaina Tedesco

Disclosure: Lazarus, Good and Pogach report no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.