T2DM: SGLT2 inhibitors offer protection against adverse cardiovascular, renal, and mortality outcomes

  • Rådholm K & al.
  • Diabetes Res Clin Pract
  • 28 Mar 2018

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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  • Sodium glucose co-transporter 2 (SGLT2) inhibitors showed a strong association with better protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death.
  • However, the downside of SGLT2 inhibition includes onset of infection, volume depletion effects, and risk for amputation.

Why this matters

  • SGLT2 inhibitors have been widely used as a treatment option for type 2 diabetes mellitus (T2DM) since 2013.
  • Although SGLT2 inhibitors are anticipated to protect against adverse cardiovascular and renal outcomes, supporting data has not been substantial.

Study design

  • Systematic review of 82 trials, 4 overviews and 6 regulatory reports involving 32,893 patients for assessing major cardiovascular events, 30,210 patients for the analyses of mortality and between 22,762 and 52,305 patients for the analyses of safety outcomes.
  • Funding: None.

Key results

  • Overall, 1968 major cardiovascular events and 2694 cardiovascular outcomes (deaths, n=766; non-fatal myocardial infarctions, n=727; non-fatal strokes, n=494; hospitalisation, n=707) were reported.
  • Use of SGLT2 inhibitors exhibited protection against major cardiovascular events (relative risk [RR], 0.85; 95% CI, 0.77-0.93), heart failure (RR, 0.67; 95% CI, 0.55-0.80), all-cause mortality (RR, 0.79; 95% CI, 0.70-0.88) and decline in kidney function (RR, 0.59; 95% CI, 0.49-0.71).
  • Use of SGLT2 inhibitors was associated with significant genital infections (RR, 3.06; 95% CI, 2.73-3.43), volume depletion events (RR, 1.20; 95% CI, 1.04-1.38) and amputation (RR, 1.44; 95% CI, 1.13-1.83).


  • No identical outcome definitions across studies.