Key result
GLP-1 RA plus SGLT2i cuts all-cause mortality ~38% vs. SGLT2i alone in heart failure.
Why the study?
Combination GLP-1 RA and SGLT2i therapy has demonstrated complementary benefits, but its effects compared with SGLT2i alone on top of standard HF care in patients with baseline HF required evaluation.
Does combination therapy of GLP-1 RA and SGLT2i reduce all-cause mortality, hospitalization, and worsening heart failure in patients with established heart failure compared to SGLT2i alone?
Meta-Analysis (n=75,833)
Does combination therapy of GLP-1 RA and SGLT2i reduce all-cause mortality, hospitalization, and worsening heart failure in patients with established heart failure compared to SGLT2i alone?
Relative Risk: 0.62 (95% CI 0.47–0.83)
p-value: p=0.0014
In patients with established heart failure, combining a GLP-1 RA with an SGLT2i significantly reduces mortality, hospitalizations, and worsening heart failure compared to SGLT2i therapy alone.
May support adding GLP-1 RA to SGLT2i in heart failure to lower mortality; extends complementary benefit data.
Background A combination of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) and a Sodium-Glucose co-transporter-2 Inhibitor (SGLT2i) has demonstrated complementary benefits. This analysis aimed to compare combination therapy (GLP-1 RA and SGLT2i) with SGLT2i alone, both on top of standard HF care, in patients with baseline HF. Methods Systematic searches (PubMed, ScienceDirect, Scopus) and citation searching were performed on February 17, 2026. Original studies directly compared combination therapy and SGLT2i alone in patients with pre-existing HF diagnosis were included. Primary endpoints were all-cause mortality, all-cause hospitalization, and worsening heart failure (WHF). NOS was used for quality assessment. R (v.4.4.1) was used for random-effect meta-analysis. Certainty of evidence was evaluated using the GRADE framework. Results Eight cohorts (n = 75,833 patients) were included. Combination therapy resulted in a lower risk of all-cause mortality [RR: 0.62; 95% CI: 0.47–0.83; p = 0.0014], all-cause hospitalization [RR: 0.89; 95% CI: 0.84–0.96; p = 0.0012], and WHF [RR: 0.74; 95% CI: 0.64–0.87; p = 0.0001] during 1-year follow-up. Combination therapy was associated with significantly improved LVEF [MD: 3.83%; 95% CI: 0.44–7.22; p = 0.0397] and reduced acute kidney injury risk [HR: 0.70; 95% CI: 0.65–0.74] without any significant increase in adverse events (including hypoglycemia, gastrointestinal side effects, pancreatitis, and urinary tract infections). GRADE assessment yielded moderate evidence for three primary endpoints. Conclusions In patients with established HF, combination of GLP-1 RA and SGLT2i therapy was associated with significant reductions in mortality, hospitalization, and WHF, without significant adverse events. Further randomized trials are urgently warranted to confirm such outcomes. Registration PROSPERO identifier no. CRD420261320840.
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Tristan et al. (2026) conducted a meta-analysis in Established Heart Failure (n=75,833). Combination therapy of GLP-1 RA and SGLT2i vs. SGLT2i alone was evaluated on All-cause mortality (RR 0.62, 95% CI 0.47-0.83, p=0.0014). In patients with established heart failure, combination therapy with GLP-1 RA and SGLT2i was associated with a lower risk of all-cause mortality (RR 0.62) compared to SGLT2i alone over 1 year.
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