Metformin appears better than sulfonylureas as first-line therapy for patients with CKD

Metformin was associated with a lower risk of mortality than sulfonylureas both overall and in all categories of estimated glomerular filtration rate, the observational study found.


Patients with type 2 diabetes and chronic kidney disease (CKD) whose initial therapy was metformin had lower mortality than those who started with a sulfonylurea, a study found.

Researchers conducted an observational, national cohort study in patients with CKD who received care from the Veterans Health Administration system for at least one year prior to starting monotherapy for type 2 diabetes with either metformin or a sulfonylurea between 2004 and 2009. The study was published online on Nov. 27 by the Journal of General Internal Medicine.

Among 175,296 new users of metformin or a sulfonylurea, there were 5,121 deaths. Metformin was associated with a lower risk of mortality than a sulfonylurea in the overall study population (hazard ratio [HR], 0.64; 95% CI, 0.60 to 0.68) and in all categories of estimated glomerular filtration rate (eGFR). The greatest risk difference was observed in the eGFR category of 30 to 44 mL/min/1.73 m2 (12.1 fewer deaths/1,000 person-years; 95% CI, 5.2 to 19.0). The differences between mortality rates for metformin initiators and sulfonylurea initiators were similar in eGFR categories of 90 mL/min/1.73 m2 or greater (3.0 fewer deaths/1,000 person-years; 95% CI, 1.5 to 4.4), 60 to 89 mL/min/1.73 m2 (4.3 fewer deaths/1,000 person-years; 95% CI, 3.2 to 5.4), and 45 to 59 mL/min/1.73 m2 (3.4 fewer deaths/1,000 person-years; 95% CI 1.3 to 5.4).

Within each eGFR category, the hazard ratios for metformin versus sulfonylurea treatment were similar across subgroups defined by age, body mass index, presence of previous cardiovascular disease, and previous heart failure, the authors wrote. However, the benefits associated with metformin were lower in patients with pre-existing cardiovascular disease and those ages 75 years and older.

The study authors concluded that initiation of metformin rather than a sulfonylurea in patients with type 2 diabetes and CKD was associated with a substantial reduction in mortality, in terms of both relative and absolute risk reduction.

“These findings, together with results from previous studies, support the FDA's guidance to consider metformin initiation among individuals with an eGFR of 45–59 mL/min/1.73m2, and suggests that metformin initiation may be beneficial among persons with even more severe CKD,” the authors concluded. “Given the number of glucose-lowering drugs available, further comparative effectiveness research is needed to guide prescribing practices, especially for high-risk patient populations.”