Semaglutide More Effective Than Empagliflozin at Lowering Cardiovascular Risks

The glucagon-like peptide-1 (GLP-1), semaglutide, seems to lower the risk of death, myocardial infarction (MI) and stroke in type 2 diabetes patients compared with empagliflozin and dulaglutide, according to the results of a study published today in the Annals of Internal Medicine. The findings could help guide prescribing decisions for high-risk patients.

Researchers from the University of Pittsburgh studied data from adult patients 45 years or older with type 2 diabetes, comorbid conditions, and a prescription for semaglutide, the most prevalent GLP-1 agonist in this health care system; dulaglutide, the second most prevalent; or empagliflozin, a type 2 diabetes medication, between January 1, 2019, and December 31, 2024. Patients were identified at 703 academic and community clinical practices.

Research was split into two trials. In the primary trial, 7,899 patients treated with semaglutide were matched to 7,899 patients treated with empagliflozin. By year three, patients on semaglutide had a major adverse cardiovascular event (MACE) risk of 5.9% compared with patients on empagliflozin, who had a MACE risk of 6.9%.

In the secondary trial, 6,093 patients treated with dulaglutide were matched with 6,093 patients treated with empagliflozin. For comparison, patients on dulaglutide had a MACE risk of 8.1% compared to patients on empagliflozin, who had a 7.8% MACE risk.

Semaglutide also resulted in greater weight loss than empagliflozin, with semaglutide accounting for approximately a 4.3 kg weight loss at 12 months and empagliflozin accounting for 3.2 kg lost. This enhanced weight loss effect could have broader metabolic and cardiovascular benefits for patients with type 2 diabetes and obesity.

Cardiovascular disease is the leading cause of morbidity and mortality in the United States, and type 2 diabetes patients are nearly double the risk for having major adverse cardiovascular events. Cardiovascular disease is also costly, and costs are expected to quadruple from $393 billion to $1490 billion, through 2050. Productivity losses are projected to increase by 54%, accounting for an increase from $234 billion to $361 billion. Stroke will likely account for the largest cost increase. Trends likely to contribute to this number are increasing trends in diabetes and obesity and an aging population.

“Consistent with a recent report by Lingvay and colleagues, semaglutide users in our study showed a greater weight loss and HbA1c reduction than those receiving empagliflozin,” corresponding author Anum Saeed, M.D., from the UPMC Heart and Vascular Institute at the University of Pittsburgh School of Medicine, writes in the study. “It is thus plausible that the greater reduction in cardiovascular events (for example, MI or stroke) that we observed is explained at least in part by the weight loss and more robust glycemic control achieved by semaglutide users.”

Additionally, the greater effectiveness of semaglutide over dulaglutide may be explained by semaglutide’s anti-inflammatory effects and tendency to reduce high-sensitivity C-reactive protein levels in patients with obesity, the study says.