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Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in
Yang Xu1,2, Tao Huang1, Yue Zhang1
1Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China (Y.X., T.H., Y.Z., D.J.).
Circulation
|February 24, 2026
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce hospitalization for heart failure (HHF) risk compared to dipeptidyl peptidase-4 inhibitors (DPP-4is) in type 2 diabetes patients. GLP-1RAs showed similar HHF risk to sodium-glucose cotransporter-2 inhibitors (SGLT-2is).
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Novel treatments are crucial for heart failure (HF) prevention in type 2 diabetes (T2D).
- Conflicting evidence exists on GLP-1RAs' efficacy in reducing HF hospitalizations (HHF) and their comparative effectiveness against SGLT-2is.
Purpose of the Study:
- To evaluate the effectiveness of GLP-1 receptor agonists (GLP-1RAs) versus DPP-4 inhibitors and SGLT-2 inhibitors in preventing HHF in T2D patients.
- To determine if HHF reduction is a class effect for GLP-1RAs or agent-specific.
Main Methods:
- Emulation of two target trials using Swedish population-based healthcare data (2010-2021).
- Comparison of GLP-1RA initiation versus DPP-4i (Trial 1) and SGLT-2i (Trial 2).
- Inverse probability of treatment weighting used to balance 72 confounders; Cox regression for hazard ratios.
Main Results:
- GLP-1RA use was associated with a lower 3-year risk of HHF compared to DPP-4i (HR 0.77; 95% CI, 0.66-0.91).
- GLP-1RA use showed similar 3-year HHF risk compared to SGLT-2i (HR 1.02; 95% CI, 0.85-1.18).
- Results were consistent across individual GLP-1RA agents and subgroups.
Conclusions:
- GLP-1RA use is linked to reduced HHF risk versus DPP-4i in T2D patients in real-world settings.
- GLP-1RAs demonstrate comparable HHF risk to SGLT-2is for T2D patients.
- Findings support GLP-1RAs for HF prevention in T2D, with potential class effects observed.
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