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The Double Mechanism of Risk Increased Ketogenesis from Lower Insulin When insulin levels drop: Fat breakdown increases Free fatty acids are converted to ketones in the liver Blood ketone levels rise Even if glucose levels are normal or mildly elevated, ketone accumulation can lead to metabolic acidosis

Gislum, S.C.L

Forward-Looking Statements: This release may contain forward-looking statements regarding industry trends, patient outcomes, program growth, expansion plans, or future developments

470 One could argue that the success of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and now of GLP-1RAs, suggests that metabolic abnormalities play an important role in driving HFpEF

Heise T, DeVries JH, Urva S, et al

Organizations involved: pharmaceutical R&D teams (Novo Nordisk, Eli Lilly), biotech startups, academic labs, specialized formulation companies, contract research organizations (CROs) for preclinical work, and CMC/CDMO partners for scale-up