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The effect of sodium‐glucose transport protein 2 inhibitors on mortality and heart failure in randomized trials versus observational studies
Author(s) -
Krogh Jesper,
Hjorthøj Carsten,
Kristensen Søren L.,
Selmer Christian,
Haugaard Steen B.
Publication year - 2021
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.14600
Subject(s) - observational study , medicine , confounding , heart failure , randomized controlled trial , placebo , diabetes mellitus , intensive care medicine , clinical trial , endocrinology , pathology , alternative medicine
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 < 0.001) and cardiovascular mortality ( p ‐interaction < 0.001) was explained by study type, whereas this was not the case for heart failure ( p ‐interaction = 0.18). Conclusion Methodological considerations such as the omission of important confounders, immortal‐time bias and residual confounding such as unmeasured social economic inequality may be the cause of the inflated results observed in observational studies and that calls for caution when observational studies are used to guide treatment of patients with type 2 diabetes.