GLP-1 Receptor Agonists Linked to Lower Heart Failure Hospitalization Risk in Type 2 Diabetes

New research indicates that patients with type 2 diabetes (T2D) who take glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a significantly lower risk of hospitalization for heart failure (HHF) compared to those taking dipeptidyl peptidase-4 (DPP-4) inhibitors. The findings, published in Circulation on February 24, 2026, add to the growing body of evidence supporting the cardiovascular benefits of GLP-1RAs.

Study Details and Methodology

Researchers, led by Yang Xu, PhD, utilized data from the Stockholm Creatinine Measurements (SCREAM) project in Sweden to conduct two emulation trials. These trials compared GLP-1RAs to both DPP-4 inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. The study population consisted of individuals with T2D, with a median age of 63-64 years and a roughly equal gender distribution (38-40% female).

GLP-1RA vs. DPP-4 Inhibitor Trial

This trial included 32,979 patients with T2D, where 42% were treated with a GLP-1RA and 58% with a DPP-4 inhibitor. Over a follow-up period of 10-36 months, the weighted incidence rate of HHF was 12.1 events per 1,000 person-years in the GLP-1RA group versus 15.8 events per 1,000 person-years in the DPP-4 inhibitor group. This translated to a three-year absolute HHF risk of 3.43% for GLP-1RA users and 4.30% for DPP-4 inhibitor users, resulting in a weighted hazard ratio (HR) of 0.77.

GLP-1RA vs. SGLT-2 Inhibitor Trial

The second trial involved 30,104 patients, with 49% receiving a GLP-1RA and 51% an SGLT-2 inhibitor. During an 8-36 month follow-up, the weighted incidence rate of HHF was similar between the groups – 12.8 events per 1,000 person-years for GLP-1RA users and 12.6 events per 1,000 person-years for SGLT-2 inhibitor users. The three-year absolute HHF risk was 3.56% versus 3.33%, with a weighted HR of 1.02.

Specific Medications Included

The GLP-1RAs included in the study were exenatide, liraglutide, lixisenatide, dulaglutide, and semaglutide. DPP-4 inhibitors included sitagliptin, vildagliptin, and linagliptin. SGLT-2 inhibitors consisted of dapagliflozin, canagliflozin, empagliflozin, and ertugliflozin.

Cardiovascular Benefits Beyond Heart Failure

Analysis of major adverse cardiovascular events (MACE) showed a positive trend with GLP-1RA use. The three-year absolute risk of MACE was 5.49% with GLP-1RAs versus 6.31% with DPP-4 inhibitors (weighted HR 0.85). However, the difference in MACE risk between GLP-1RAs and SGLT-2 inhibitors was not statistically significant (4.88% vs. 4.91%, weighted HR 0.98).

Implications for Patient Care

The study authors suggest that GLP-1RAs may be beneficial in reducing HHF risk in patients with T2D, regardless of their history of heart failure. This is particularly relevant given the increasing prevalence of T2D due to factors like aging, obesity, and diabetic kidney disease. The findings support the use of GLP-1RAs for both primary and secondary prevention of heart failure in this patient population. Source