GLP-1 Receptor Agonists Vs SGLT2 Inhibitors: A Comparison of Cardiovascular Benefits

A study presented at the American Diabetes Association Virtual 81st Scientific Sessions offered a head-to-head comparison of cardiovascular (CV) benefits associated with the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i).

It is well established that cardiovascular risk is disproportionately higher in individuals with diabetes. According to a recent report from the American College of Cardiology/American Heart Association, individuals with diabetes had a 93% higher risk of primary cardiovascular complications among Caucasians and a 139% higher risk among African Americans compared with the non-diabetic population with similar sociodemographic and health status, explained lead study author Christina DeRemer, PharmD, BCPS, BCACP, FASHP, from the University of Florida College of Pharmacy during an oral presentation of the study findings.

“Despite awareness for this elevated cardiovascular risk, until recently higher literature has failed to establish glucose-lowering as means for reducing cardiovascular disease-related events,” DeRemer said.

However, emerging data has changed the sequencing of type 2 diabetes medications for patients with established CV disease, elevating the use of SGLT2 inhibitors and GLP-1 RAs in this patient population. “These 2 pharmacologic classes are recommended as second-line therapy following metformin,” DeRemer explained. However, the 2 agents lack direct comparative analyses, which leaves clinicians with a gap in information regarding differentiation. 

For the study, the investigators aimed to compare CV benefits associated with the use of GLP-1RAs versus SGLT2 inhibitors as add-on therapies to metformin in adults with type 2 diabetes (T2D) with and without a history of CV complications. Real-world clinical CV benefits were analyzed among 11,911 metformin users with T2D who initiated either GLP-1RA or SGLT2i between March 29 and December 31, 2013. Patients were divided into 2 cohorts: those without a history of CV disease and those with a history of CV disease.

The primary end point was a major cardiovascular composite (MCC), including acute myocardial infarction (MI), hospitalization for congestive heart failure (CHF), and stroke. Patients were followed until the primary end point, end of the study period, study drug discontinuation, or the initiation of another study drug.

According to the results, no difference in the risk of MCC or any secondary end point, which included the individual components of MCC, was observed between GLP-1RA users and SGLT2i users who did not have established CV disease. However, the authors reported significantly lower risks of MCC (HR: 0.67, 95% CI: 0.47-0.97) and CHF (HR: 0.47, 95% CI: 0.28-0.79) among SGLT2i users compared with GLP-1RA users, among those with established CV complications.

DeRemer indicated that data on mortality was not available in this database, which made direct comparisons to other trials challenging. In both cohorts, there were no differences in age between users of SGTL2 inhibitors and GLP-1RA; however, participants who received SGTL2 inhibitors were more likely to be male and to live in the southern region of the United States.

Over time, more criteria have added to clarify of the use of SGLT2 inhibitors and GLP-1 RAs, specifically in chronic kidney disease (CKD) or congestive heart failure populations, DeRemer explained. However, a lack of clear distinction for use continues due to the lack of head-to-head trials.

“Our trial shows no difference in use between SGLT2 inhibitors and GLP-1 receptor agonists for major cardiovascular composite being stroke, myocardial infarction, and congestive heart failure in patients without established cardiovascular disease,” she concluded.

However, the findings align with information from randomized controlled trials compared with placebo, and adjustments in guidelines that suggest patients with established congestive heart failure should be treated with SGLT2 inhibitors as the first option when compared with GLP-1 RAs, DeRemer added.

Reference

1. DeRemer CE, Guo J, Vouri SM, Haller MJ, et al. 220-OR – Comparing cardiovascular benefits between GLP-1RA and SGLT2i as an add-on to metformin among US adults with type 2 diabetes (T2D). Presented at: American Diabetes Association Virtual 81st Scientific Sessions; June 25-29, 2021; online.