SGLT2 inhibitors are associated with lower rates of death for patients with type 2 diabetes

A new class of medication, known as sodium-glucose transporter-2 (SGLT2) inhibitors, is associated with lower rates of death and hospitalisation for heart failure when used to treat patients with type 2 diabetes, both with or without existing cardiovascular disease, and regardless of the specific SGLT2 inhibitor used, according to a study, “Hospitalization for Heart Failure and Death in New Users of SGLT2 Inhibitors in Patients With and Without Cardiovascular Disease—CVD-REAL Study,” presented at the American Diabetes Association’s 77th Scientific Sessions at the San Diego Convention Center. 

The CVD-REAL study analysed the outcomes of 306,156 patients with type 2 diabetes from five different countries—the United States, United Kingdom, Norway, Sweden and Denmark—who were treated with SGLT2-inhibitors. SGLT2 is a protein responsible for glucose regulation in the body. SGLT2 inhibitors reduce renalglucose reabsorption by causing excess blood glucose to be expelled through urine.

Using data from clinical practice, researchers compared rates of heart failure (HF) and death in patients with and without prior cardiovascular disease (CVD) to HF rates in new users of SGLT2-inhibitors and other glucose lowering drugs (oGLD). Data on HF and subsequent death rates were collected using medical records, medical claims, electronic health records and national registers. 

Propensity scores were used to match patients treated with SGLT2 inhibitors and oGLD. After matching, baseline characteristics were balanced between groups, and 306,156 patients, >150,000 person years (PY) (100,947 PY for SGLT2i; 89,208 PY for oGLD) and 950 new HF events were analyzed. The hazard ratios (HR) for HF, death and the composite of death or heart failure were estimated by country and pooled as a weighted average. 

An association between SGLT2-inhibitors and lower rates of death due to heart failure and hospitalisation for heart failure was seen in all of the five participating countries. Furthermore, the benefits of SGLT2-inhibitor treatments were consistent regardless of the type of SGLT2-inhibitor used, which varied from country to country. SGLT2-inhibitors, when compared to oGLD, were associated with 31 percent lower rates of HF in patients with CVD and 45percent without CVD (HR 0.69; 95% CI 0.59-0.80; HR 0.55 95% CI 0.34-0.88). Similar results were seen for death and death due to HF regardless of whether the patients had a history of cardiovascular disease or not. All patients treated with SGLT2-inhibitors were less likely to have heart failure or subsequent death, compared to the oGLD patients.

“This study offers further evidence regarding the potential of SGLT2-inhibitors to improve outcomes in patients with diabetes,” said Dr. Matthew A. Cavender, MD, MPH, assistant professor of medicine, at the University of North Carolina School of Medicine. “While our results are striking in their similarity to a prior randomized study evaluating the benefit of SGLT-2 inhibitors in patients with diabetes and known cardiovascular disease, these results go one step further to show that SGLT2-inhibition may benefit all patients with diabetes, regardless of whether they have known cardiovascular disease. It’s also important to note that there was a significant difference in the particular SGLT2-inhibitor used in each country, suggesting that the benefits seen with SGLT2-inhibitors are likely to be a class effect. Previous research has shown that patients with diabetes have a 30 percent higher risk for heart failure when compared to patients without diabetes. These findings suggest that use of SGLT-2 inhibitors may provide the opportunity to reduce the incidence of heart failure among patients with diabetes.” 

Ongoing randomized clinical trials with SGLT2-inhibitors are likely to provide a considerable amount of additional information regarding its clinical effectiveness. In follow-up to this study, there are plans to further evaluate the effectiveness of SGLT2-inhibitors on other important clinical events and to broaden the study’s focus to evaluate the association between other drugs designed for use in patients with diabetes and history of cardiovascular events.