Nashville, TN—One-fifth of adults in the United States with type 2 diabetes (T2D) also have impaired kidney function, and, until recently, some of the most common medications were not recommended for them. Managing their treatment to reduce cardiovascular risks, as well as lowering blood sugar, added to that challenge, a new study suggests.

An article in JAMA, which includes results from an observational study using medical-record information from nearly 50,000 U.S. military veterans, offers a possible solution to the dilemma.

A team led by researchers from the Veteran Administration Tennessee Valley VA Health Care System and Vanderbilt University Medical Center determined that metformin, which is widely recommended as a first-line drug therapy for T2D, is linked to a 20% decreased risk of major adverse cardiovascular events when compared with sulfonylureas.

The study tracked acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death, determining that, with metformin, 5.8 fewer of these events per 1,000 person-years occurred versus sulfonylureas.

“Until recently the use of metformin in patients with diabetes and impaired kidney function was cautioned against due to safety concerns. The effectiveness of metformin demonstrated in this study will further support a potential change in prescribing practices for these patients. We believe these results should encourage providers to continue use of metformin in mild-to- moderate kidney disease,” said lead researchers Christianne Roumie, MD, MPH, associate professor of Medicine and Pediatrics at VUMC.

Background information in the report notes that, before 2016, prescriptions for patients with kidney disease were limited by safety concerns, and the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remained unclear.

Researchers sought to compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea.

The retrospective cohort study used VA healthcare data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. It identified 174,882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold; that was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine ≥1.4 mg/dL for women, or ≥1.5 mg/dL for men.

The study team followed patients from reduced kidney–function threshold until MACE, treatment change, loss to follow-up, death, or study end in December 2016.

The focus was on new users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function.

With 67,749 metformin and 28,976 sulfonylurea-persistent monotherapy users, the weighted cohort included 24,679 metformin and 24,799 sulfonylurea users. The patients had a median age of 70 years (interquartile range [IQR], 62.8-77.8). The group was nearly all male and mostly—82%—white with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% (IQR, 6.1%-7.2%) at cohort entry.

During follow-up—a median of 1 year for metformin versus 1.2 years for sulfonylurea—1,048 MACE outcomes occurred (23.0 per 1,000 person-years) among metformin users and 1,394 events (29.2 per 1,000 person-years) among sulfonylurea users.

Researchers calculated that the cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas.

“Among patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE,” the authors conclude.

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