SGLT2 Inhibitors Associated with Lower Rates of Death, Hospitalization for Heart Failure in Patients with Type 2 Diabetes

The results of an international study showing the benefits of sodium-glucose transporter-2 (SGLT2) inhibitors was presented at American Diabetes Association’s 77th Scientific Sessions in San Diego.

According to the study, “Hospitalization for Heart Failure and Death in New Users of SGLT2 Inhibitors in Patients With and Without Cardiovascular Disease—CVD-REAL Study,” the benefits were conferred regardless of pre-existing cardiovascular disease (CVD) or which type of SGLT2 inhibitor was used.

SGLT2 inhibitors are a new class of oral medications used in the treatment of type 2 diabetes (T2D). SGLT2 is a protein responsible for glucose regulation in the body, and SGLT2 inhibitors reduce renal glucose reabsorption by causing excess blood glucose to be expelled through urine. This mechanism of action helps the kidneys lower blood glucose levels.

The CVD-REAL study analyzed 306,156 patients with T2D from 5 countries—the United States, United Kingdom, Norway, Sweden, and Denmark—who were treated with SGLT2 inhibitors. Using clinical practice data, the researchers compared the rates of heart failure (HF) and death in patients with and without prior CVD to HF rates in new users of SGLT2 inhibitors and other glucose lowering drugs (oGLD).

The data on HF and subsequent death rates were collected using medical records, medical claims, electronic health records, and the national registers of the participating countries.

Propensity scores were used to match patients treated with SGLT2 inhibitors and oGLD. The baseline characteristics were balanced between groups, and 306,156 patients, totaling >150,000 person years (PY) (100,947 PY for SGLT2 inhibitors; 89,208 PY for oGLD) and 950 new HF events were analyzed.

The hazard ratios (HR) for HF, death, and the composite of death from HF were estimated by country and pooled as a weighted average.

An association between SGLT2 inhibitors and lower rates of death due to HF and hospitalization for HF were seen in all 5 of the participating countries. Furthermore, the benefits of treatment with SGLT inhibitors were consistent regardless of the type of inhibitor used, which varied from country to country.

When compared with oGLD, the SGLT2 inhibitors were associated with 31% lower rates of HF in patients with existing CVD (HR 0.69; 95% CI 0.59-0.80), and 45% lower rates of HF in patients without existing CVD (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.

Notably, all of the patients treated with SGLT2 inhibitors were less likely to have HF or subsequent death compared with the oGLD patients.

“This study offers further evidence regarding the potential of SGLT2 inhibitors to improve outcomes in patients with diabetes,” Matthew A. Cavender, MD, MPH, assistant professor of medicine at the University of North Carolina School of Medicine, said in the results presentation. “While our results are striking in their similarity to a prior randomized study evaluating the benefit of SGLT2 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.”

He addressed the possibility of a class effect in the results, saying, “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% higher risk for heart failure when compared to patients without diabetes. These findings suggest that use of SGLT2 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 the follow-up to this study, Cavender said that 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 who have a history of cardiovascular events.