Log in to MyACC
Cardiac Outcomes After Adding SGLT2 Inhibitors to GLP-1RA
Quick Takes
- Initiation of SGLT2i in patients already on GLP-1RA therapy is associated with reductions in the risk of a composite cardiovascular endpoint outcome and HF hospitalizations, compared with initiation of sulfonylureas.
- This analysis provides support for SGLT2i use in patients already on GLP-1RA therapy and has implications for preventing further cardiovascular morbidity and mortality in patients with diabetes.
Study Questions:
What is the impact of the addition of sodium-glucose co-transporter 2 inhibitors (SGLT2i) to glucagon-like peptide agonists (GLP-1RA) on cardiovascular events compared to GLP-1RA alone?
Methods:
The investigators identified patients adding either SGLT2i or sulfonylureas to baseline GLP-1RA within three US claims datasets (2013-2018) and were 1:1 propensity score matched adjusting for >95 baseline covariates. The primary outcomes were: 1) composite cardiovascular endpoint (CCE; comprised of myocardial infarction [MI], stroke, and all-cause mortality), and 2) heart failure (HF) hospitalization. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in each dataset and pooled via fixed-effects meta-analysis.
Results:
Among 12,584 propensity score matched pairs (mean [standard deviation] age 58.3 [10.9] years; 48.2% male) across the three datasets, there were 107 CCE events (incidence rate per 1,000 person-years [IR], 9.9; 95% CI, 8.1-11.9) among SGLT2i initiators compared to 129 events (IR, 13.0; 95% CI, 10.9-15.3) among sulfonylurea initiators corresponding to an adjusted pooled HR of 0.76 (95% CI, 0.59-0.98); this decrease in CCE was driven by numerical decreases in the risk of MI (HR, 0.71; 95% CI, 0.51-1.003) and all-cause mortality (HR, 0.68; 95% CI, 0.40-1.14) but not stroke (HR, 1.05; 95% CI, 0.62-1.79). For the outcome of HF hospitalization, there were 141 events (IR, 13.0; 95% CI, 11.0-15.2) among SGLT2i initiators versus 206 (IR, 20.8; 95% CI, 18.1-23.8) events among sulfonylurea initiators, corresponding to an adjusted pooled HR of 0.65 (95% CI, 0.50-0.82).
Conclusions:
The authors concluded that among diabetic patients already on GLP-1RA, addition of SGLT2i compared to addition of sulfonylurea conferred greater cardiovascular benefit.
Perspective:
This real-world study from insurance claims datasets reports that the initiation of SGLT2i in patients already on GLP-1RA therapy is associated with reductions in the risk of a composite cardiovascular endpoint outcome (comprised of MI, stroke, and all-cause mortality) and HF hospitalizations, compared with initiation of sulfonylureas. Of note, due to the observational nature of the design, the current study is susceptible to residual confounding due to lack of randomization. Despite these limitations, this analysis provides support for SGLT2i use in patients on GLP-1RA therapy and has implications for preventing cardiovascular morbidity and mortality in diabetes. A prospective randomized study assessing the cardiovascular effects of the combination of SGLT2i and GLP-1RA would provide more definitive evidence.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure
Keywords: Cardiovascular System, Diabetes Mellitus, Glucagon-Like Peptides, Glucose, Heart Failure, Metabolic Syndrome, Myocardial Infarction, Myocardial Ischemia, Primary Prevention, Sodium-Glucose Transporter 2, Stroke, Sulfonylurea Compounds
< Back to Listings
