SOURCE: Tuot DS, et al. Potential impact of prescribing metformin according to eGFR rather than serum creatinine. Diabetes Care 2015;38:2059-2067.

Metformin is the pharmacologic foundation of most guidelines for management of type 2 diabetes (T2DM), based on its efficacy, safety record, and the availability of favorable clinical trial outcomes data. Although serious adverse effects from metformin are rare, significant renal insufficiency increases the risk for lactic acidosis, which can be fatal. Original FDA labeling suggested renal safety boundaries based on serum creatinine (sCR), but when first devised, the boundaries (sCR < 1.4 for women, < 1.5 for men) were based on doses of metformin up to 3000 mg/d. Currently, the maximum approved dose (2550 mg/d) is not thought to be meaningfully more efficacious than 2000 mg/d, hence the commonplace prescription of metformin 1000 mg twice a day.

Recent recommendations suggest that metformin is safe when eGFR is > 45 mL/min, but the risk rises significantly when eGFR < 30 mL/min (30 mL/min to 45 mL/min eGFR is an “indeterminate” zone). Using data from the National Health and Nutrition Examination Survey (NHANES) population (n = 3902), the investigators determined that as many as 15% of patients who were excluded from metformin based on sCR would have been eligible for metformin based on a eGFR of > 45 mL/min.

In an era of progressively more expensive interventions for T2DM, clinicians may wish to re-evaluate the boundaries of safe prescribing for metformin.