SGLT2 inhibitors may have class effect for reduction of cardiac risk

The industry-funded study used international data to compare rates of heart failure hospitalization and mortality in patients on sodium glucose cotransporter-2 (SGLT2) inhibitors or other glucose-lowering drugs.


Sodium glucose cotransporter-2 (SGLT2) inhibitors were associated with reduced risk for heart failure hospitalization and death in a recent international industry-funded study.

Researchers used data from the United States, Norway, Denmark, Sweden, Germany, and the United Kingdom to evaluate whether cardiac benefits seen with empagliflozin in a trial of patients with type 2 diabetes and atherosclerotic cardiovascular disease would be present in real-world practice and with other drugs in the same class. Medical claims, records from primary care practices and hospitals, and data from national registries were used, with treatment groups matched by propensity score for initiation of SGLT2 inhibitors. SGLT2 inhibitors were compared with other glucose-lowering drugs. Hospitalization for heart failure was the primary outcome, with all-cause death and the composite outcome of hospitalization for heart failure or all-cause death as secondary outcomes. The results of the study, which was funded by AstraZeneca, were published online May 16 by Circulation.

A total of 309,056 patients who had been newly started on SGLT2 inhibitors or other glucose-lowering drugs were included in the study, with 154,528 patients in each group. Mean age was 57 years. Forty-four percent of patients were women, and 13% had established cardiovascular disease. Among patients taking SGLT2 inhibitors, canagliflozin was the most common, followed by dapagliflozin and empagliflozin (53%, 42%, and 5%, respectively). During 190,164 person-years of follow-up, 961 hospitalizations for heart failure occurred. Data on deaths were not available for Germany, but in the other countries, 1,334 patients died and 1,983 patients experienced the composite outcome of hospitalization for heart failure or death (incidence rate, 0.87 per 100 person-years and 1.38 per 100 person-years, respectively). Compared with other glucose-lowering drugs, SGLT2 inhibitors were associated with lower rates of hospitalization for heart failure, death, and both outcomes combined (hazard ratios, 0.61 [95% CI, 0.51 to 0.73], 0.49 [95% CI, 0.41 to 0.57], and 0.54 [95% CI, 0.48 to 0.60]; P<0.001 for all comparisons).

The authors noted that their study was observational and did not examine safety, that events besides heart failure hospitalization and death were not considered, and that longer follow-up is needed, among other limitations. However, they concluded that, in patients with type 2 diabetes, SGLT2 inhibitors appear to be associated with lower rates of heart failure hospitalization and death compared to other glucose-lowering drugs and that the lack of heterogeneity in their results may suggest a class effect. “Since the overwhelming majority of patients did not have established [cardiovascular disease], this suggests that the benefits of [SGLT2 inhibitors] on the prevention of heart failure may extend to lower risk patients than those enrolled in randomized trials so far,” the authors wrote.