The effect of sodium‐glucose transport protein 2 inhibitors on mortality and heart failure in randomized trials versus observational studies

Aim Randomized clinical trials (RCTs) allocating type 2 diabetes patients to treatment with sodium‐glucose transport protein 2 (SGLT‐2) inhibitors or placebo have found significant effects on the risk of heart failure and modest effects on mortality. In the wake of the first trials, a number of observational studies have been conducted, some of these reporting a mortality reduction of 50% compared to active comparators. In this review, we systematically assess and compare the results on all‐cause mortality, cardiovascular mortality and heart failure hospitalization observed in RCTs with the results obtained in observational studies. Method We performed a systematic bibliographical search including cardiovascular outcome trials and observational studies assessing the effect of SGLT‐2 inhibitors on mortality and heart failure. Results Seven RCTs and 23 observational studies were included in the current review. The observed heterogeneity between study results for all‐cause mortality (p‐interaction