Empagliflozin plus GLP-1RA prevents hospitalization, death in adults with T2D

Patients with type 2 diabetes (T2D) who initiated treatment with empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), and a glucagon-like peptide-1 receptor agonist (GLP-1RA) show reduced hospitalization for heart failure (HHF) and all-cause mortality risks relative to those treated with empagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i), reports a study presented at EASD 2024.

In addition, the risks of myocardial infarction (MI) and stroke are comparable between empagliflozin plus GLP-1RA and empagliflozin plus DPP-4i.

“We chose DPP-4i because it has been shown to be consistently cardiovascular neutral,” said lead study author Dr Phyo Than Htoo from Brigham and Women's Hospital, Boston, US.

Htoo and his team identified T2D patients aged ≥18 years (≥65 years in Medicare), who initiated empagliflozin and had not used SGLT2i, GLP-1RA (including GLP-1RA for weight loss and tirzepatide), or DPP-4i in the last 6 months using the Medicare, Optum, and Marketscan databases from 2014 to 2022. Patients who initiated GLP-1RA or DPP-4i while on treatment with empagliflozin were also identified.

Follow-up began on the day following the initiation of GLP-1RA or DPP-4i. An on-treatment scheme was put to use until discontinuation or either drug class or empagliflozin, a gap in insurance coverage, death, or end of the study period.

The authors estimated hazard ratios (HRs) using Fine and Gray subdistribution hazards regression and rate differences (RDs) per 1,000 person-years using Mantel-Haenszel methods to evaluate the composite of MI or stroke, HHF, and mortality after 1:1 propensity score matching.

Reduced HHF, mortality

In total, 19,551 matched pairs of patients initiating combination therapy with empagliflozin plus GLP-1RA versus empagliflozin plus DPP-4i were included in the analysis. After matching, the rates of MI and stroke did not differ between treatment arms, with a similar MI-stroke risk (HR, 1.00, 95 percent confidence interval [CI], 0.77‒1.29; RD, ‒0.04, 95 percent CI, ‒3.08 to 2.99). [EASD 2024, abstract 52]

The risk of HHF was lower among patients who initiated empagliflozin plus GLP-1RA than those who received empagliflozin plus DPP-4i (HR, 0.82, 95 percent CI, 0.71‒0.96; RD, ‒6.47, 95 percent CI, ‒11.55 to ‒1.42). When HHF was defined using diagnosis codes only in the primary hospital discharge position, the risk decreased further (HR, 0.49, 95 percent CI, 0.34‒0.71; RD, ‒4.34, 95 percent CI, ‒6.61 to ‒2.16).

Additionally, all-cause mortality risk was also lower in the empagliflozin plus GLP-1RA arm than in the empagliflozin plus DPP-4i (HR, 0.61, 95 percent CI, 0.46‒0.81; RD, ‒4.79, 95 percent CI, ‒7.56 to ‒2.09).

“In adults with T2D in US clinical practice, those initiating empagliflozin plus GLP-1RA had lower risk of HHF and all-cause mortality compared to those initiating empagliflozin plus DPP-4i,” Htoo said.

“Patients using combination therapy with both empagliflozin and GLP-1RA may have additive benefits compared to using empagliflozin alone,” the authors said.

Clinical guidelines recommend the combined use of empagliflozin and GLP-1RA due to the known cardiovascular benefits of these medications.