SGLT-2 Inhibitors: A Type 2 Diabetes Drug that Helps the Heart

By Hae-Lin Cho and Ben Pallant

CVD-REAL study showed SGLT-2 inhibitors reduce the risk of hospitalization for heart failure in over 300,000 people with type 2 diabetes

Results from an important real-world study (CVD-REAL) suggest that the newest family of diabetes drugs, SGLT-2 inhibitors, can significantly reduce the risk of hospitalization due to heart failure as well as overall risk of death.

Dr. Mikhail Kosiborod recently presented the results from CVD-REAL, a very exciting real-world study comparing AstraZeneca’s Farxiga, J&J’s Invokana, and Lilly/BI’s Jardiance (SGLT-2 inhibitors) to other type 2 diabetes medicines, including insulin, DPP-4 inhibitors (e.g., Januvia, Onglyza, Tradjenta, Nesina), and GLP-1 agonists (e.g., Byetta, Victoza, Trulicity). The study, which started in late 2015, looked at data from over 300,000 participants with type 2 diabetes from six different countries.

While fewer than 1% of participants in the study were hospitalized for heart failure or died, there were significant differences in the likelihood of these events depending on the type of drug. Notably, the researchers found that participants taking SGLT-2s were 39% less likely to be hospitalized due to heart failure and had a 51% lower overall risk of death.

In some ways, this does not come as a major surprise; randomized, controlled trials have demonstrated that SGLT-2s like Jardiance can substantially reduce the risk of death. However, the CVD-REAL study was a “real-world” observational trial, providing evidence that the benefits are seen in everyday settings as well as the “controlled” setting of a formal trial. The diaTribe Foundation has advocated for seeing more “real-world” data and we were thrilled to see the results of this study.

The vast majority of CVD-REAL participants (87%) did not have any history of heart disease, a difference from most outcomes trials that study those at the very highest risk for heart disease. In other words, the trial suggests that the SGLT-2s have protective benefits even for those who haven’t had heart complications in the past – a big deal because it means this therapy might be very helpful to a much larger group of people than previously thought.

The size of the trial is also quite notable (with over 300,000 people), as it is far larger than controlled trials. However, Dr. Kosiborod acknowledged that real-world studies have other limitations – for example, there is no randomization to ensure the groups are evenly balanced in terms of their characteristics and risk factors. The researchers tried to take such factors into account as best as they could, and future studies will dive deeper into the data from CVD-REAL.

Although SGLT-2s are considerably more expensive than other type 2 diabetes drugs, they generally have good reimbursement for those with insurance, and copay programs do exist (see here for Jardiance, here for Invokana, and here for Farxiga).