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The effect of sodium-glucose transport protein 2 inhibitors on mortality and heart failure in randomized trials

Jesper Krogh1, Carsten Hjorthøj2,3, Søren L Kristensen4

  • 1Department of Endocrinology, Rigshospitalet University Hospital, Copenhagen, Denmark.

Diabetic Medicine : a Journal of the British Diabetic Association
|May 15, 2021
PubMed
Abstract

Insights

Sodium-glucose transport protein 2 (SGLT-2) inhibitors show significant benefits for heart failure in type 2 diabetes patients. However, observational studies may overestimate mortality benefits due to methodological issues, urging caution in treatment guidance.

Area of Science:

  • Cardiology
  • Endocrinology
  • Clinical Pharmacology

Background:

  • Sodium-glucose transport protein 2 (SGLT-2) inhibitors have demonstrated significant effects on heart failure risk and modest effects on mortality in type 2 diabetes patients.
  • Numerous observational studies have reported substantial mortality reductions with SGLT-2 inhibitors, sometimes exceeding findings from randomized clinical trials (RCTs).

Purpose of the Study:

  • To systematically assess and compare the findings on all-cause mortality, cardiovascular mortality, and heart failure hospitalization from RCTs and observational studies of SGLT-2 inhibitors in type 2 diabetes.
  • To investigate the reasons for discrepancies in mortality outcomes between RCTs and observational studies.

Main Methods:

  • A systematic bibliographical search was conducted to identify relevant cardiovascular outcome trials and observational studies.
  • Included studies evaluated the effects of SGLT-2 inhibitors on mortality and heart failure in patients with type 2 diabetes.

Main Results:

  • Seven RCTs and 23 observational studies were included. Study type explained heterogeneity in all-cause and cardiovascular mortality results (p-interaction < 0.001), but not for heart failure hospitalization (p-interaction = 0.18).
  • Observational studies often reported inflated mortality reduction compared to RCTs.

Conclusions:

  • Methodological limitations in observational studies, including confounding, immortal-time bias, and residual confounding, likely contribute to exaggerated mortality benefit findings.
  • Caution is advised when using observational study results to guide SGLT-2 inhibitor treatment decisions for type 2 diabetes patients.
Keywords:
SGLT-2 inhibitorsdiabetesheart failuremortalitypropensity scorereal-world studies

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