Optimal strategies for preventing heart failure (HF) in patients with type 2 diabetes (T2D) remain under evaluation. Using Swedish population-based health care data (2010-2021), two target trials were emulated to compare glucagon-like peptide-1 receptor agonists (GLP-1RA) with dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) for risk of hospitalization for heart failure (HHF). The study was published in the Circulation.

Target trial 1 included 32,979 adults with T2D newly initiating GLP-1RA (42%) or DPP-4i (58%) (mean age 64 years; 40% female). Target trial 2 included 30,104 adults initiating GLP-1RA (49%) or SGLT-2i (51%) (mean age 63 years; 38% female). Cox regression estimated intention-to-treat hazard ratios (HR) with inverse probability of treatment weighting balancing 72 confounders. Major adverse cardiovascular events (MACE) served as a positive control outcome. Analyses were conducted for the GLP-1RA class and individual agents including liraglutide and semaglutide.

GLP-1RA initiation was associated with lower 3-year absolute HHF risk compared with DPP-4i (3.4% vs 4.3%; weighted HR 0.77; 95% CI 0.66-0.91). Compared with SGLT-2i, 3-year HHF risks were 3.6% versus 3.3% (weighted HR 1.02; 95% CI 0.85-1.18). Absolute risk differences were larger in patients with higher baseline HF risk. Results were consistent across individual agents, per-protocol analyses, and most subgroups. GLP-1RA was associated with lower MACE risk versus DPP-4i (weighted HR 0.85; 95% CI 0.74-0.99).

GLP-1RA use was associated with lower HHF risk versus DPP-4i and similar risk versus SGLT-2i. Findings were consistent across analyses in routine clinical care.