In patients with type 2 diabetes (T2D), the risk of hospitalization for heart failure (HHF) was significantly lower with GLP-1RAs than DPP-4 inhibitors while it was similar compared with SGLT-2 inhibitors, according to results from real-world emulation trials published Feb. 24 in Circulation.
Using population data on patients with T2D through the SCREAM project (Stockholm Creatinine Measurements) in Sweden, Yang Xu, PhD, et al., conducted two emulation trials: GLP-1RAs vs. DDP-4 inhibitors and GLP1-RAs vs. SGLT-2 inhibitors. GLP-1RAs included were exenatide, liraglutide, lixisenatide, dulaglutide and semaglutide. DPP-4 inhibitors were sitagliptin, vildagliptin and linagliptin. SGLT-2 inhibitors were dapagliflozin, canagliflozin, empagliflozin and ertugliflozin.
In the first trial, with 32,979 patients with T2D (median age 64 years, 40% women), 42% took a GLP-1RA and 58% a DDP-4 inhibitor. Over the follow-up of 10-36 months, the weighted incidence rate was 12.1 vs. 15.8 events per 1,000 person-years, respectively, and the three-year absolute HHF risk was 3.43% vs. 4.30% (weighted hazard ratio [HR], 0.77).
In the second trial, consisting of 30,104 patients (median age 63 years, 38% women), 49% took a GLP-1RA and 51% a SGLT-2 inhibitor. During the follow-up of eight to 36 months, the weighted incidence rate was 12.8 vs. 12.6 events per 1,000 person-years and three-year absolute HHF risk was 3.56% vs. 3.33% (weighted HR, 1.02), respectively.
Notably, the absolute risk difference was largest among patients with a higher predicted risk of HF at baseline. Findings were consistent across most subgroups, between single agents and in per-protocol analyses.
Positive control outcome analyses found three-year absolute risks for major adverse cardiovascular events were 5.49% vs. 6.31% with GLP-1RAs vs. DDP-4 inhibitors (weighted HR 0.85) and 4.88% vs. 4.91% with GLP1-RAs vs. SGLT-2 inhibitors (weighted HR, 0.98).
Noting that roughly 90% of the patient population did not have HF, “our findings suggest that GLP-1RAs could be used to reduce the risk of HHF in patients with T2D, regardless of [HF] history, thereby addressing both primary and secondary prevention needs,” write the study authors. “This is especially important because T2D is a strong risk factor for developing [HF], and the number of patients with T2D is expected to increase as a result of population aging and a rise in risk factors such as obesity and comorbidities such as diabetic kidney disease.”