GLADIATOR: Anti-ulcer agent geranylgeranylacetone explored in HFpEF

In the proof-of-concept GLADIATOR trial, geranylgeranylacetone (GGA) did not improve health outcomes in patients with heart failure with preserved ejection fraction (HFpEF).

“Currently, only sodium-glucose cotransporter-2 [SGLT2] inhibitors and the mineralocorticoid receptor antagonist [MRA] finerenone have demonstrated to improve outcomes for patients with HFpEF,” said Dr Geert Voordes (University Medical Center Groningen, the Netherlands) [1]. “Thus, despite the rising incidence of this disease, treatment options remain limited.” GGA is an over-the-counter anti-ulcer drug that has displayed positive results regarding diastolic function and sarcomere compliance in animal models [2]. The phase 2 GLADIATOR study (NCT05672134) randomised 43 patients with HFpEF >50 years of age 1:1 to GGA or placebo. After 3 months, participants underwent a 6-week washout period, after which they crossed over. The primary endpoints of left ventricular diastolic function (E/e’) and endothelial function (reactive hyperaemia index [RHI]) were assessed after another 3 months.

There was no difference between the study arms regarding changes in E/e’ ratio (mean 8.31 vs 8.07; P=0.46) or RHI (mean 2.31 vs 2.15; P=0.92). Secondary efficacy measures displayed neutral results as well. Finally, GGA was generally well-tolerated, as was expected for this over-the-counter drug.

In conclusion, GGA did not improve disease outcomes for patients with HFpEF in this proof-of-concept study.

1. Voordes GHD, et al. GLADIATOR: Effects of geranylgeranylacetone on diastolic and microvascular function in patients with heart failure with a preserved ejection fraction. Hottest trials and trial updates (2), Heart Failure 2025, 17–20 May, Belgrade, Serbia.
2. Waddingham MT, et al. Physiol Rep. 2023;11(22):e15788.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 21 May 202517 July 2025