Metformin Can Be a Choice for Type 2 Diabetes Patients with Kidney Disease

Metformin has historically been avoided for patients with type 2 diabetes and chronic kidney disease (CKD), but new research suggests it can be safe in some CKD patients.

Benjamin Lazarus, MBBS, MPH, and his colleagues assessed whether the drug increased the risk of acidosis in patients with CKD in a new study published in JAMA Internal Medicine.

As part of the study, they compared the rate of lactic acidosis in patients taking metformin to others taking sulfonylurea and found that time-dependent metformin was not associated with incident acidosis overall (adjusted hazard ratio [HR], 0.98; 95% CI, 0.89-1.08). In addition, there was no increased risk of acidosis for patients with estimated glomerular filtration rates (eGFRs) above 30 mL/min/1.73m². The risk for acidosis did increase for those patients who took metformin and had an eGFR below 30 mL/min/1.73m² (adjusted HR, 2.07; 95% CI, 1.33-3.22).

"Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m²," they concluded.

Metformin has advantages as a first-line therapy because of its convenience, low cost, and low incidence of hypoglycemia. It also is generally well tolerated by most patients and is effective in lowering blood glucose, making it the first-line therapy for most patients.

There has been concern, however, about its use in patients with CKD, primarily due to a boxed warning on its labeling that metformin should not be used in patients with impaired renal function.

"In recent years there have been concerns raised questioning the absolute warnings for patients with moderately impaired renal function," Chester B. Good, MD, MPH, tells Drug Topics. "Because of the boxed warnings, clinicians might stop metformin prematurely in patients with moderately impaired renal function, and use less effective agents that were potentially less safe."

According to Good, who wrote an accompanying commentary to the study, most cases of lactic acidosis typically occur in settings where a patient is in renal failure, often in combination with other comorbid conditions such as sepsis or hypotension. For this reason, investigators wanted to learn more about the rates of acidosis in those with mild to moderate renal impairment.

"Lazarus and colleagues reviewed real-world data from a large cohort of patients in an integrated medical system, comparing new user patient cohorts using either metformin or a sulfonylurea," Good says.

He believes their conclusion to cautiously use metformin in type 2 diabetes patients with eGFR of at least 30 mL/min/1.73m² is reasonable. He cautions, however, that there is nothing magical about the limit of an eGFR of 30 mL/min/1.73m².

"Many clinicians might not want to initiate therapy for patients who have declining renal function, especially as it approaches an eGFR of 30," Good says. "Patients should be aware of the warnings for using metformin in clinical settings that might acutely diminish renal function, such as radiocontrast studies, or low-flow or hypotensive situations such as sepsis or heart failure."

If clinicians are concerned a patient may not understand the warnings or comply with regular medical follow-up, they might be better off prescribing another medication, he says.

Good believes any treatment recommendations for patients with diabetes should be made through a shared decision making process that takes into account multiple healthcare providers, pharmacists, and the patients themselves.

"In addition to issues such as safety, efficacy, cost, convenience, and side effects of medications, there are also considerations regarding treatment goals, such as the targeted glycated hemoglobin," he says. "As such, each decision should be individualized to meet the goals of the patients, under the informed information provided by the clinician."