Do SGLT2 inhibitors lower the risk of cardiovascular disease in patients with type 2 diabetes?

This study evaluated the effects on cardiovascular disease (CVD) of SGLT2 inhibitors compared to two other drugs used to treat type 2 diabetes (T2D), sulfonylureas, and DPP4 inhibitors. It was determined that SGLT2 inhibitors were associated with a lower risk of developing CVD.

People with T2D have an increased risk of developing CVD. Treatment of T2D with drugs to lower blood glucose (sugar) levels may reduce this risk. SGLT2 inhibitors, sulfonylureas, and DPP4 inhibitors are drugs used to treat T2D that work in different ways to lower blood glucose. It is still not known which is the best drug to use in T2D to reduce the risk of CVD. Some evidence suggests that SGLT2 inhibitors may reduce the risk of CVD, but this is still under investigation.

A database was used to gather information on 258,800 adults with T2D. 62,767 patients who received SGLT2 inhibitors were compared to the same number of patients who were treated with sulfonylureas. Similarly, 66,633 patients with SGLT2 inhibitors were compared to the same number of patients treated with DPP4 inhibitors. They were followed up for an average of 12 months. Is was noted whether patients developed any complications from CVD, such as stroke or heart attack. Patients were also monitored for any hospitalizations due to heart failure or for leg amputations.

The SGLT2 inhibitor group had a 50% lower risk of having a non-fatal heart attack or stroke compared to the sulfonylurea group, and a 43% lower risk compared to the DPP4 inhibitor group. The type of SGLT2 inhibitor used, such as dapagliflozin (Foxiga) or canagliflozin (Invokana), did not affect the risk. The risk of CVD complications was lower in the SGLT2 inhibitor group than the other groups, whether or not they had CVD at the start of the study.

Patients aged 65 years or younger in the SGLT2 inhibitor group had a 41% lower risk of having a non-fatal heart attack or stroke compared to the sulfonylurea group, and a 35% lower risk compared to the DPP4 inhibitor group. However, no difference was seen between groups, in those older than 65 years.

The SGLT2 inhibitor group had a 52% lower risk being hospitalized for heart failure than the sulfonylurea group, and a 46% lower risk than the DPP4 inhibitor group. The SGLT2 inhibitor group also had a 26% lower risk of needing a leg or foot amputation than the sulfonylurea group. The risk of needing a leg or foot amputation was the same for the SGLT2 inhibitor and DPP4 inhibitor groups.

The study concluded that SGLT2 inhibitors are associated with a lower risk of CVD (non-fatal heart attacks and strokes) than sulfonylureas and DPP4 inhibitors in people with T2D. This benefit is seen mostly in people aged 65 years or younger, whether or not they already have CVD.

The database did not contain all the relevant information. For example, whether or not participants smoked tobacco was not known, and this could have affected the CVD risk.

Discuss the potential cardiovascular benefits of glucose-lowering drugs with your physician.