Peer Reviewed

Metabolic Disease

Metformin Reduces MACE Risk in Patients With Diabetes and Reduced Kidney Function

Individuals with diabetes and reduced kidney function who are taking metformin monotherapy have a reduced risk of major adverse cardiovascular events (MACE) compared with those taking sulfonylurea monotherapy, according to a new study.

To reach this conclusion, the researchers conducted a retrospective cohort study of 49,478 US veterans aged 18 years or older (median age, 70 years) who had regularly received care within the national Veterans Health Administration. Additional data were collected from Medicare, Medicaid, and the National Death Index from 2001 through 2016.


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Patients were included in the study analysis if they met the following criteria:

  • Had new-onset type 2 diabetes as determined by new prescription of metformin, glipizide, glyburide, or glimepiride.
  • Had recent decline in kidney function as determined by glomerular filtration rate and creatinine thresholds.

In all, the weighted cohort included 24,679 patients taking metformin and 24,799 taking a sulfonylurea. 

Patients were followed up from the time the reduced kidney function threshold was met until MACE (hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death), treatment change, loss to follow up, mortality, or study end (December 2016).

The median follow-up period was 1.0 year for those taking metformin and 1.2 years for those taking a sulfonylurea. During this time, there were 1048 MACE outcomes among metformin users (23.0 per 1000 person-years) and 1394 events among sulfonylurea users (29.2 per 1000 person-years).

Compared with sulfonylureas, the cause-specific adjusted hazard ratio of MACE for metformin users was 0.80. In turn, the adjusted rate difference was 5.8 fewer events per 1000 person-years of metformin use compared with sulfonylurea use.

“This study and the results add to the limited observational evidence for the beneficial association of metformin compared with sulfonylurea and cardiovascular outcomes among those who develop reduced kidney function,” the researchers concluded.

—Colleen Murphy


Roumie CL, Chipman J, Min JY, et al. Association of treatment with metformin vs sulfonylurea with major adverse cardiovascular events among patients with diabetes and reduced kidney function. JAMA. 2019;322(12):1167-1177. doi:10.1001/jama.2019.13206.