“Numerous studies have found that Avandia use is associated with an increased cardiovascular risk, especially for heart failure,” says Joshua Wallach, PhD, lead author of the new study, published in February 2020 in BMJ. Dr. Wallach is an assistant professor at the Yale School of Public Health in New Haven, Connecticut. “However, the effect of Avandia on (heart attacks) has been more uncertain,” Wallach adds. For the current analysis, Wallach and colleagues examined data from 136 clinical trials to see whether Avandia (rosiglitazone) was associated with an increased risk of heart attacks, heart failure, heart-related deaths, and fatalities from other causes. Unlike earlier safety studies of Avandia, the current analysis included raw data — or detailed records for individual participants — from 33 trials conducted by the drug’s manufacturer, GlaxoSmithKline. This analysis using raw data found that individuals taking Avandia were 33 percent more likely to have a heart attack, heart failure, or death from heart problems or other causes. When researchers looked at each of these risks separately, they found the strongest and most worrisome evidence for heart failure: a 54 percent greater risk of this developing in people taking Avandia. While the raw data analysis also showed a 17 percent higher risk of heart attacks with Avandia, the evidence wasn’t as strong. The risk also appeared lower when researchers analyzed both the 33 trials with raw data and 103 additional trials without individual patient-level data. This suggests that clinical trials using raw data from individual patients are crucial for understanding whether medicines are safe, Wallach says. In the case of Avandia, the complete safety picture is coming into focus too late. “Although we found that Avandia is associated with an increased cardiovascular risk, especially for heart failure, it is now approximately 20 years after Avandia was first approved, and it is no longer available in Europe and rarely prescribed in the United States,” Wallach says. RELATED: How Diabetes and Heart Disease Are Connected
A Brief History of Avandia’s Approval and Use in the United States and Europe
Avandia won U.S. Food and Drug Administration (FDA) approval in 1999 to help people with type 2 diabetes manage their blood sugar levels. The drug won marketing approval from the European Medicines Agency (EMEA) the following year. Despite regulatory warnings about heart failure risks, annual sales surged to about $3.3 billion by 2006, researchers noted in the BMJ. Next, an analysis published in 2007 in The New England Journal of Medicine found the drug associated with a 43 percent increased risk of heart attacks and a 64 percent higher risk of deaths from cardiovascular causes. That year, the EMEA recommended against using Avandia in people with heart disease. Sales of the drug were suspended in Europe by 2010 due to cardiovascular risks, the study team notes in BMJ. Between 2010 and 2011, the FDA issued new warnings about cardiovascular risks of Avandia and required individuals taking the drug to receive extra monitoring for side effects. These restrictions were lifted in 2013 after two Avandia studies, including the RECORD trial, published in June 2009 in The Lancet, suggested that it was just as safe as two other types of diabetes drugs, metformin and a family of medicines known as sulfonylureas. But no safety trials at this point had proven that metformin or sulfonylureas lacked heart risks, says Sanjay Kaul, MD, a cardiologist at Cedars-Sinai Medical Center in Los Angeles. Trial results suggesting that Avandia wasn’t any safer or more dangerous than the other two drugs “would not be very reassuring,” Dr. Kaul adds. RELATED: How to Beat Type 2 Diabetes With Diet and Lifestyle Changes
People With Type 2 Diabetes Have Alternative Treatment Options
People with type 2 diabetes have many other treatment options, notes Deborah Wexler, MD, clinical director of the Massachusetts General Hospital Diabetes Center in Boston. “As always, lifestyle modification — eliminating consumption of sugary beverages, eating a balanced diet, aiming to lose 5 to 7 percent of body weight, and increased physical activity, such as walking 30 minutes five times per week — is the safest,” Dr. Wexler says. Many people with type 2 diabetes aren’t able to lower their blood sugar levels enough with lifestyle changes alone, however. “If lifestyle measures are insufficient, medications such as metformin and many other classes of glucose-lowering medications are available,” Wexler says. When it comes to offsetting heart risks, SGLT2 inhibitors such as Jardiance (empagliflozin) and Invokana (canagliflozin) may help manage cardiovascular health or reduce the likelihood of heart disease in those at a high risk, according to an article published in January 2019 in Diabetes Care. But these drugs have potential side effects that doctors must consider for each individual, as well. “At this point, there is very little reason to use (Avandia),” Wexler says. RELATED: The Pros and Cons of SGLT2 Inhibitors
