Metformin for diabetics with renal damage scores over Sulphonylureas in terms of heart safety

By Dr. Ananya Mandal, MDSep 25 2019

There are several drugs that are being used for treatment of type 2 diabetes. Many type 2 diabetics suffer from kidney disorders that are caused by persistent high levels of blood sugar.

The number of persons in the United States with diabetes is around 30 million of which around 20 percent suffer from various degrees of impaired renal function. Use of combination drugs in diabetics with kidney disease has been a topic for debate for the past few decades. Renal safety has been studied in a latest study with over 50,000 individuals with diabetics to put to rest these debates.

Diabetic using lancelet on finger. Image Credit: sirtravelalot / Shutterstock

The results of the study titled, “Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular Events Among Patients With Diabetes and Reduced Kidney Function,” was published in the latest issue of the Journal of American Medical Association.

This new study looked at medical record information from 49,478 U.S. military veterans with diabetes and reduced kidney function or renal damage. For patients with diabetes and renal damage the first line therapy is metformin followed by other classes of drugs including sulphonylureas such as Glimepiride, Glibenclamide, Gliclazide, Glipizide, Glyburide etc. For each of the participants, the researchers from Vanderbilt University Medical Center looked at all cardiac events such as heart attacks, strokes, transient ischemic attacks or TIA and deaths due to cardiovascular reasons.

The authors wrote, “Metformin is eliminated by the kidneys and can accumulate as estimated glomerular filtration rate (eGFR) declines... the US Food and Drug Administration (FDA) issued a safety warning restricting metformin for patients with serum creatinine levels of 1.5 mg/dL or greater for men or 1.4 mg/dL or greater for women.” This guidance was changed in 2016, they wrote adding, “FDA changed its guidance based on evidence regarding metformin safety in patients with mild to moderate kidney disease; however, the effectiveness of metformin for clinical outcomes in those with reduced kidney function remains unknown.”

Christianne Roumie, associate professor of Medicine and Pediatrics at VUMC and study leader, in a statement said...

“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.”

The study results have revealed that use of metformin has reduced the risk of major adverse cardiovascular events or MACE by 20 percent when compared to sulphonylureas. This reduced risk of MACE with metformin also means a 5.8 fewer events of MACE per 1,000 person years when compared to sulphonylureas, say the researchers.

The team had looked at a 174,882 strong population enrolled under the national Veterans Health Administration between 2001 and 2016 who were diagnosed with Type 2 Diabetes. The data was obtained from records linked to Medicare, Medicaid, and National Death Index data. These individuals were all started on either metformin or a sulfonylurea (54 percent glipizide, 45 percent glyburide, and 1 percent glimepiride). Many of them developed renal complications and had impaired renal function. The authors of the study defined low renal function 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”. They zoned in on 24,679 patients who were on metformin and 24,799 who were on a sulphonylurea. Patients who were on other combination of anti-diabetic drugs were excluded from the study. The authors defined MACE as, “hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death.” The median age of the study population was around 70 years with 98 percent men and 82 percent whites in the population.

Roumie and colleagues took into account other factors that could affect the risk of MACE. This included factors such as Body mass index, age, gender, blood pressure, race etc. for all the patients finally included in the study. Patients were followed up for an average of 1 year and 1.2 year for metformin and sulphonylureas respectively. Results revealed that among metformin users there were 1,048 adverse events compared to 1,394 events among the sulfonylurea users. The adverse event risk was 23.0 and 29.2 per 1,000 person-years, respectively for metformin and sulphonylureas.

The authors concluded in their study, “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.”