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

Related ObG Topics:

Treating Type 2 Diabetes

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

Does the Type of Dietary Fat Affect Mortality and Heart Disease in Individuals with Type 2 Diabetes?