Metformin: double duty drug
New treatment option for patients with type 2 diabetes and heart failure
Story by Tara Narwani/Illustration by Davey Thompson
Early in his career as a young hospital pharmacist, Dr. Dean Eurich encountered first-hand how a drug regulation can sometimes deprive patients of access to a potentially beneficial drug.
Dr. Eurich observed physicians struggling to provide treatment options for patients suffering from both type 2 diabetes and heart failure. Almost 25% of patients with heart failure are subsequently diagnosed with diabetes. Physicians were restricted to prescribing either insulin or another class of drugs called sulfonylureas that induce the pancreas to release more insulin.
“The downside with type 2 diabetes is that virtually everyone has to go onto another drug,” explains Dr. Eurich, now an assistant professor in the School of Public Health at the University of Alberta. “It’s a progressive disease. Your glycemic (sugar) levels continue to get worse. Physicians were stuck. They really only had two drugs, and after that there wasn’t a whole lot for them to do.”
By contrast, those who only had type 2 diabetes had additional treatment options available to them, particularly the drug metformin. There are many benefits associated with metformin: improved outcomes in overweight patients, the drug is taken orally rather than injected like insulin, and patients don’t experience attacks of low blood sugar, which is sometimes observed with sulfonylureas and often seen with insulin therapy. As a result, metformin is the initial drug of choice for doctors treating type 2 diabetes patients in Canada and around the world.
Researchers began to ask whether metformin would also benefit type 2 diabetes patients with heart failure. The problem is that, since the drug was introduced in Canada in 1972, metformin has been absolutely contraindicated (prohibited) for use in heart failure patients.
The story of metformin has been a case of “guilt by association.” Metformin’s predecessor drug, phenformin, was pulled from the market in the 1960s when it was linked to a fatal reaction called lactic acidosis. When metformin came out, regulatory agencies such as Health Canada were cautious: they slapped it with a contraindication in heart failure as well.
According to Dr. Eurich, “The perception of metformin being a risky drug has stuck for the last 30 years with physicians, patients, and advocacy groups, despite the fact there was no evidence to say that the drug was actually harmful in patients with heart failure.”
Dr. Eurich and his colleagues at the University of Alberta began to investigate whether there was any risk associated with metformin use in patients with type 2 diabetes and heart failure. They undertook an observational study using the Saskatchewan health database that collects information on prescription drug use, hospital claims, and physician visits in addition to data on patient demographics and vital statistics. This type of resource is extremely useful for conducting epidemiological studies. Epidemiology is the study of the causes, distribution, and control of disease in populations.
It turns out many patients with type 2 diabetes and heart failure were already being treated with metformin despite the contraindication. Dr. Eurich speculates that doctors who were treating their patients successfully with metformin prior to a diagnosis of heart failure may have been reluctant to change their drug regime after the diagnosis.
The study showed that metformin wasn’t associated with increased hospitalization rates compared with those patients taking sulfonylureas. Furthermore, no patients were hospitalized or died from lactic acidosis in the study. Interestingly, fewer patients treated with metformin (33%) died in comparison to those using sulfonylurea (52%).
“The logical conclusion from this study is that the drug appears safe,” says Dr. Eurich, “but the question now is, ‘Is it really more effective in patients with heart failure?’”
The issue of whether metformin benefits type 2 diabetes patients with heart failure is best addressed through a randomized control trial in which researchers randomly give some patients metformin and give other patients placebos and compare the results.
Unfortunately, since 50% of heart failure patients were already taking metformin, Dr. Eurich and his colleagues found that such a trial was infeasible after a year-long attempt; other researchers worldwide are encountering this obstacle as well.
Nonetheless, in 2009, Health Canada lifted the contraindication of metformin use in heart failure patients on the basis of work by Dr. Eurich and others.
“This has opened another avenue of drug treatment for patients with diabetes and heart failure,” says Dr. Eurich. “And if the drug is truly beneficial in terms of improving survival, that’s a big satisfaction knowing that your research could improve both the quality of a patient’s life, and the longevity of that life.”