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Grand Rounds

Do SGLT2 Inhibitors Decrease Risk for Major Cardiovascular Events in People with T2D?

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BACKGROUND AND PURPOSE:

  • Previous RCTs have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors reduce the incidence of major adverse cardiovascular events in people with type 2 diabetes and previous cardiovascular disease
    • Observational studies have shown that SGLT2 inhibitors are superior to other antidiabetic drugs for reduction of major CVD events
  • Filion et al. (BMJ, 2020) compared the risk of cardiovascular events between SGLT2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors, another common antidiabetic drug, among people with type 2 diabetes

METHODS:

  • Multi-database retrospective cohort study and meta-analysis
  • Data source
    • Canadian Network for Observational Drug Effect Studies (CNODES) | Administrative healthcare databases
  • Participants
    • New users of a SGLT2 inhibitor (canagliflozin, dapagliflozin, empagliflozin)
    • Users of a DPP-4 inhibitor (alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin)
  • Study design
    • Users of SGLT2 inhibitors matched to users of DPP-4 inhibitor
    • Comparisons between groups were calculated using adjusted hazard ratios (HR) and 95% confidence intervals
    • Site specific results were pooled using random effects meta-analysis
  • Primary outcome
    • Major adverse cardiovascular events (MACE)
      • Composite of myocardial infarction, ischemic stroke, or cardiovascular death
  • Secondary outcomes
    • Individual components of MACE
    • Heart failure
    • All-cause mortality

RESULTS:

  • 209,867 SGLT2 inhibitor users | 209,867 DPP-4 inhibitor users
    • Mean duration of follow-up: 0.9 years
  • Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of
    • MACE
      • SGLT2: incidence rate: 11.4 per 1000-person years
      • DPP-4: incidence rate: 16.5 per 1000-person years
      • HR 0.76 (95% CI, 0.69 to 0.84)
    • Myocardial infarction
      • SGLT2: 5.1 per 1000-person years
      • DPP-4: 6.4 per 1000-person years
      • HR 0.82 (95% CI, 0.70 to 0.96)
    • Cardiovascular death
      • SGLT2: 3.9 per 1000-person years
      • DPP-4: 7.7 per 1000-person years
      • HR 0.60 (95% CI, 0.54 to 0.67)
    • Heart failure
      • SGLT2: 3.1 per 1000-person years
      • DPP-4: 7.7 per 1000-person years
      • HR 0.43 (95% CI, 0.37 to 0.51)
    • All-cause mortality
      • SGLT2: 8.7 per 1000-person years
      • DPP-4: 17.3 per 1000-person years
      • HR 0.60 (95% CI, 0.54 to 0.67)
  • SGLT2 inhibitor benefit was more limited for ischemic stroke
    • SGLT2: 2.6 per 1000-person years
    • DPP-4: 3.5 per 1000-person years
    • HR 0.85 (95% CI, 0.72 to 1.01)
  • Similar benefits for MACE were observed with different SGLT2 inhibitors
  • Subgroup analyses to assess relationship with duration of use
    • Results were similar for first year of follow-up compared to subsequent years

CONCLUSION:

  • Short-term use of SGLT2 inhibitors in people with type 2 diabetes was associated with a decreased risk of cardiovascular events vs DPP-4 inhibitors
  • The authors conclude

SGLT2 inhibitors are associated with a decreased risk of serious cardiovascular events compared with dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world setting

The consistent results across individual SGLT2 inhibitors suggest a class effect for the cardiovascular benefits of SGLT2 inhibitors

Learn More – Primary Sources:

Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study

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An Update on Rosiglitazone and Cardiovascular Risk: New Meta-Analysis with Individual Patient Data
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