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Effect of Addition of SGLT2i or GLP1RA on Cardiovascular Events
Quick Takes
- Among a cohort of older patients with diabetes but without established CVD, addition of GLP1RA to baseline diabetes therapy was associated with reduced MACE and HF hospitalization events compared with adding DPP4i.
- However, adding SGLT2i was not associated with reduced MACE and HF hospitalizations compared with adding DPP4i.
- Given multiple limitations of the current analysis, these findings should be considered hypothesis generating, and further prospective evaluation of these medications as part of primary CVD prevention strategy is indicated.
Study Questions:
What is the effectiveness of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) in preventing major adverse cardiac events (MACE) for those without pre-existing cardiovascular disease (CVD)?
Methods:
The investigators conducted a retrospective cohort study of US veterans from 2001 to 2019. Veterans aged ≥18 years receiving care from the Veterans Health Administration with data linkage to Medicare, Medicaid, and the National Death Index were included and those adding GLP1RA, SGLT2i, or dipeptidyl peptidase-4 inhibitors (DPP4i) onto metformin, sulfonylurea, or insulin treatment alone or in combination were analyzed. Episodes were stratified by history of CVD. Study outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization. Cox models compared the outcome between medication groups using pairwise comparisons in a weighted cohort adjusted for covariates.
Results:
The cohort included 28,759 GLP1RA versus 28,628 DPP4i weighted pairs and 21,200 SGLT2i versus 21,170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. GLP1RA were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82; 95% confidence interval [CI], 0.72-0.94), yielding an adjusted risk difference (aRD) of 3.2 events (95% CI, 1.1-5.0) per 1,000 person-years. SGLT2i were not associated with MACE and HF (aHR, 0.91; 95% CI, 0.78-1.08; aRD, 1.28; 95% CI, -1.12 to 3.32) compared with DPP4i.
Conclusions:
The authors report that addition of GLP1RA was associated with primary reductions of MACE and HF hospitalization compared with DPP4i use, while SGLT2i addition was not associated with primary MACE prevention.
Perspective:
This analysis reports that among a national cohort of older Veterans Health Administration patients with diabetes but without established CVD, addition of GLP1RA to baseline diabetes therapy was associated with reduced MACE and HF hospitalization events compared with adding DPP4i. However, adding SGLT2i was not associated with reduced MACE and HF hospitalizations compared with adding DPP4i. Of note, although not statistically significant, SGLT2i use over a median follow-up of 0.42 years was associated with numerically fewer HF hospitalizations. Given multiple limitations of the current analysis, these findings should be considered hypothesis generating, and further evaluation of these medications as part of primary CVD prevention strategy is indicated.
Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure
Keywords: Acute Coronary Syndrome, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Glucagon-Like Peptide-1 Receptor, Heart Failure, Myocardial Infarction, Myocardial Ischemia, Primary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Sulfonylurea Compounds, Vascular Diseases, Veterans
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