Key result
GLP-1 RAs cut MACCE by ~50% in HFpEF compared to standard treatment.
Why the study?
The comparative effectiveness of GLP-1 RAs versus SGLT2 inhibitors and conventional therapy on cardiovascular outcomes, mortality, and hospitalisations in HFpEF patients was unclear.
Do GLP-1 RAs and SGLT2 inhibitors reduce MACE, mortality, and heart failure hospitalization compared to standard treatment in patients with HFpEF?
Meta-Analysis (n=364,024)
Do GLP-1 RAs and SGLT2 inhibitors reduce MACE, mortality, and heart failure hospitalization compared to standard treatment in patients with HFpEF?
Both GLP-1 RAs and SGLT2 inhibitors provide meaningful and comparable clinical benefits in reducing major adverse cardiovascular events and heart failure hospitalizations in patients with HFpEF.
GLP-1 RAs warrant consideration for MACCE reduction in HFpEF; extends network evidence of benefits comparable to SGLT2 inhibitors.
Aim We aimed to compare glucagon-like peptide-1 receptor agonist ( GLP-1 RAs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and conventional therapy for major adverse cardiovascular events (MACE), all-cause mortality, and heart failure (HF) hospitalisation in patients with heart failure with preserved ejection fraction (HFpEF) (left ventricular ejection fraction [LVEF]≥40%). Secondary objectives include comparing the two drug classes for cardiovascular mortality and all-cause hospitalisation. Methods We systematically searched the literature until 6 March 2026 for randomised control trials and propensity-matched cohort studies. Data was extracted by two independent reviewers. Network meta-analyses compared GLP1-RAs vs SGLT-2 inhibitors vs standard treatment (control) for each outcome. Prespecified subgroup analyses examined drug efficacy by follow-up period, drug formulation and LVEF diagnostic threshold for HFpEF. Results 28 studies encompassing 364,024 patients were included. GLP-1 RAs significantly reduced MACCE, all-cause mortality and HF hospitalisation compared with standard treatment (Odd ratio [OR]=0.50 [0.32, 0.78], p=0.002; OR=0.61 [0.45, 0.83], p=0.002; OR=0.50 [0.36, 0.70], p<0.0001 respectively). SGLT2 inhibitors significantly reduced HF hospitalisation (OR=0.69 [0.48, 0.97], p=0.034) and MACE (OR=0.49 [0.27, 0.91], p=0.024), but not all-cause mortality. No statistically significant differences were observed when comparing GLP-1 RAs and SGLT2 for all primary outcomes. Conclusions Both GLP-1 RAs and SGLT2 inhibitors provide meaningful clinical benefit in HFpEF, with comparable overall effectiveness. Further direct comparative trials and analyses stratified by cardiometabolic phenotypes may clarify whether specific patient subgroups derive greater benefit from one therapeutic class over the other.
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Cai et al. (2026) conducted a meta-analysis in Heart failure with preserved ejection fraction (HFpEF) (n=364,024). GLP-1 RAs and SGLT2 inhibitors vs. Standard treatment was evaluated on MACCE (OR 0.50, 95% CI 0.32-0.78, p=0.002). In patients with HFpEF, GLP-1 RAs significantly reduced MACCE compared to standard treatment (OR 0.50, 95% CI 0.32-0.78, p=0.002), with overall effectiveness comparable to SGLT2 inhibitors.
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