Patients who have chronic kidney disease (CKD, also known as renal disease) have “unacceptably high” death rates from cardiovascular causes, according to Everly Ramos, MD, of Vanderbilt University Medical Center in Nashville, Tennessee. To understand why this is and to seek treatments, she and her colleagues conducted a study about possibly using the well-known diabetes medication metformin to help patients with CKD. They presented the results at the latest virtual meeting of the American Society of Nephrology, an event known as “Kidney Week 2020.”
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Type 2 diabetes is the most common cause of CKD, both in the United States and around the world. The U.S. Centers for Disease Control (CDC) estimates that about a quarter of all Americans with diabetes also suffer from CKD.
Ramos and her team were struck by the fact that the death rates from cardiovascular disease among kidney patients could not be entirely explained by the traditional risk factors associated with CKD. They wondered about other factors, especially insulin resistance, which is a condition in which the cells of the body don’t respond well to insulin. As Ramos pointed out, “Insulin resistance is common in patients with CKD and is predictive of CV [cardiovascular] and all-cause mortality in nondiabetic patients with end-stage renal disease.” Insulin resistance contributes to what’s known as endothelial dysfunction, a condition in which the arteries are unable to fully dilate because the lining doesn’t function properly. Insulin resistance also promotes stiffness in the arteries.
Metformin and CKD
The researchers observed that metformin is a standard treatment for CKD patients who have diabetes, but little is known about metformin’s possible benefits in cardiovascular disease in patients with prediabetes, moderate kidney disease or obesity (or all three). They identified 60 patients who were overweight or obese and had moderate CKD (eight out of ten were men and the median age was 66). Half were randomly selected to receive 500 milligrams of metformin per day. The other half received a placebo (an inactive substance). The trial lasted 16 weeks.
After the results were in, Ramos and her colleagues determined that treatment with metformin nearly doubled what’s known as brachial artery flow-mediated dilation (FMD) from 6.24% to 12.06%. FMD, which is measured by ultrasound, is commonly used to evaluate endothelial function and the relaxation of arteries due to increased blood flow. In addition, the researchers found that metformin reduced another factor called lectin-adiponectin ratio, or LAR. Measuring LAR is a fairly new diagnostic tool based on research indicating that a leptin-adiponectin imbalance appears to be related to a greater risk of developing type 2 diabetes and cardiovascular disease in obese patients. According to Ramos, LAR is “a practical and accurate index of insulin resistance.” The ratio has also been linked to a risk of atherosclerosis (the accumulation of plaque in the arteries) and even some types of cancer. All together, Dr. Ramos said, the results of the study suggest that not only does metformin have an effect on blood sugar, but it also seems to have cardiovascular benefits in patients with prediabetes.
Previously we reported on other promising reports about metformin ─ it might lower the risk of death from COVID-19 in women with type 2 diabetes, it could help reduce the side effects of steroids, and it appears to shield diabetes patients from harmful complications after surgery. This new study indicates that it might have at least one other use.
Want to learn more about keeping your kidneys healthy with diabetes? Read “Managing Diabetic Kidney Disease,” “Kidney Disease: Your Seven-Step Plan for Prevention” and “Ten Things to Know About Kidney Disease.”