What if a diabetes medication can improve cardiovascular events? Since patients with type II diabetes are more prone to cardiac events, the use of diabetes medication to help reduce cardiovascular burden would definitely be beneficial. One of such medications is the drug, Metformin.
Metformin, also know with the trade name of Glucophage, is the first-line of treatment for type II diabetes. It is also often prescribed to patients with metabolic syndrome and patients with polycystic ovarian syndrome to control insulin resistance. Metformin works by increasing insulin sensitivity and decreasing glucose production by the liver. While its molecular mechanism of action is not completely understood, one way metformin exerts its effects is through regulating AMP-activated protein kinase (AMPK), an enzyme that plays an important role in insulin signaling and detecting cellular energy levels. By regulating AMPK, metformin also lowers inflammation and thus there is an emerging body of evidence suggesting that metformin regulates the immune system and reduces inflammation and can potentially protect against diseases such as inflammatory bowel disease and atherosclerosis.
Until recently, there has been associations that metformin may protect against cardiovascular disease, although exactly how was never been directly studied. A recent study by a group of researchers in Columbia University in New York, published recently in the ATVB journal, looked at the role of metformin and how it may affect cardiovascular disease. The authors show that exposure of liver cells to metformin increased the expression of ABCG5 and ABCG8, two cholesterol transporter molecules responsible for the efflux of cholesterol. The authors also saw the same effect when they gave metformin to mice fed a western diet, also know as high cholesterol, high fat diet. This increase in expression of ABCG5 and ABCG8 was accompanied by an increase in cholesterol clearance from the plasma in these treated mice. This study provides first evidence of how metformin could have a direct cardiovascular disease protective effect.
Since metformin, through regulating AMPK, has an anti-inflammatory effect, this study shows that metformin may have a combined protective impact regarding cardiovascular disease; the first through increasing cholesterol clearance and the second through reducing immune mediated inflammation, overall resulting in lower cholesterol levels and less inflammatory mediators responsible for atherosclerosis progression and thus reducing cardiovascular disease risk. It would be interesting to see if patients who are taking metformin for diabetes treatment have a decrease in cardiovascular events in a controlled manner. Finally, this study highlights the potential of a drug like metformin, not only as a diabetes medication but as a cardiovascular protective drug as well.
Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development.