biostudies-literatureUnknown153(8)Hundertmark MJ<h4>Background</h4>We report IMPROVE-DiCE (Improve Diabetic Cardiac Energetics), a 2-part open-label, phase 2a trial evaluating the safety and effectiveness of ninerafaxstat, a novel therapeutic designed to enhance cardiac energetics. Between May and September 2021, part 1 enrolled patients with type 2 diabetes and obesity without heart failure with preserved ejection fraction (HFpEF). Between January 2023 and June 2024, part 2 enrolled patients with type 2 diabetes, obesity, and HFpEF.<h4>Methods</h4>Forty-two participants received 200 mg ninerafaxstat twice daily (part 1, n=21, 43% women, 72±0.5 years of age, 4-8 weeks; part 2, n=21, 29% women, 71±6 years of age, 12 weeks). Myocardial energetics (phosphocreatine-to-ATP ratio [PCr/ATP], primary outcome) and function (rest and dobutamine sCirculation550-563https://www.ebi.ac.uk/biostudies/studies/S-EPMC12928817biostudies-literatureIMPROVE-DiCE, a 2-Part, Open-Label, Phase 2a Trial Evaluating the Safety and Effectiveness of Ninerafaxstat in Patients With Cardiometabolic Syndromes.PMC12928817Hundertmark MJRao PHenry JAGerszten REDehbi HMYavari ABirkhoelzer SMShi XChamberlin PTyler DJSarwar RRider OJLewis AJValkovic LFrenneaux MPMatthews VMozes FMiller JJJJPatel JRobbins JMPortwood CZheng SGrist JNeubauer SSiu AGfalseIMPROVE-DiCE, a 2-Part, Open-Label, Phase 2a Trial Evaluating the Safety and Effectiveness of Ninerafaxstat in Patients With Cardiometabolic Syndromes.<h4>Background</h4>We report IMPROVE-DiCE (Improve Diabetic Cardiac Energetics), a 2-part open-label, phase 2a trial evaluating the safety and effectiveness of ninerafaxstat, a novel therapeutic designed to enhance cardiac energetics. Between May and September 2021, part 1 enrolled patients with type 2 diabetes and obesity without heart failure with preserved ejection fraction (HFpEF). Between January 2023 and June 2024, part 2 enrolled patients with type 2 diabetes, obesity, and HFpEF.<h4>Methods</h4>Forty-two participants received 200 mg ninerafaxstat twice daily (part 1, n=21, 43% women, 72±0.5 years of age, 4-8 weeks; part 2, n=21, 29% women, 71±6 years of age, 12 weeks). Myocardial energetics (phosphocreatine-to-ATP ratio [PCr/ATP], primary outcome) and function (rest and dobutamine s2026-01-01T00:00:00Z2026 Feb2026-07-16T18:35:42.567Z2026-07-09T11:15:10.496ZS-EPMC129288174141003710.1161/CIRCULATIONAHA.125.074041