USA: Cardiovascular Benefits of SGLT2i vs Sulfonylureas in Diabetes Patients

Initiation of SGLT2i versus sulfonylureas in diabetes patients on GLP-1RA therapy confers greater cardiovascular benefit, suggests a recent study in the journal Circulation. The results provide support for the use of SGLT2i in patients already on GLP-1RA therapy and is relevant for the prevention of cardiovascular mortality and morbidity in diabetes patients.

In large randomized trials, several sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide agonists (GLP-1RA) have shown cardiovascular benefit in patients with established cardiovascular disease or multiple risk factors. However, only a few participants of the trial were on both agents, and it is not clear whether SGLT2i addition to GLP-1RA therapy has further cardiovascular benefits. To determine the same, Chintan V. Dave, Rutgers University, New Brunswick, NJ, and colleagues identified patients adding either SGLT2i or sulfonylureas to baseline GLP-1RA. The identification was done from 3 US claims datasets (2013-2018), and the participants were 1:1 propensity score matched (PSM) adjusting for over 95 baseline covariates.

The primary outcomes were:

• Composite cardiovascular endpoint (CCE; comprised of myocardial infarction, stroke, and all-cause mortality)
• Heart failure hospitalization

Key Findings of the Study

Among 12,584 propensity-score matched pairs (mean [SD] age 58.3 [10.9] years; male (48.2%)) across the 3 datasets, there were 107 CCE events [incidence rate per 1,000 person-years (IR) = 9.9] among SGLT2i initiators compared to 129 events [IR = 13.0] among sulfonylurea initiators, corresponding to an adjusted pooled HR of 0.76. This decrease in CCE was driven by numerical decreases in the risk of MI (HR 0.71) and all-cause mortality (HR 0.68) but not stroke (HR 1.05).

For the outcome of heart failure hospitalization, there were 141 events [IR = 13.0] among SGLT2i initiators versus 206 [IR = 20.8] events among sulfonylurea initiators, corresponding to an adjusted pooled HR of 0.65.

"In this large real-world cohort of diabetic patients already on GLP-1RA, addition of SGLT2i - compared to addition of sulfonylurea - conferred greater cardiovascular benefit. The magnitude of the cardiovascular risk reduction was comparable to the benefit seen in cardiovascular outcome trials of SGLT2i versus placebo where baseline GLP-1RA use was minimal," wrote the authors.

The study titled, "Risk of Cardiovascular Outcomes in Type 2 Diabetes Patients Following Addition of SGLT2 Inhibitors Versus Sulfonylureas to Baseline GLP-IRA Therapy," is published in the journal Diabetes Care.

DOI: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.047965