What question did this study set out to answer?

The aim is to investigate the role of hyperinsulinemia in metabolic dysfunction by optimizing diazoxide treatment.

June 7, 2026

2470-P: Optimizing Diazoxide to Study Hyperinsulinemia and De Novo Lipogenesis in MASLD

JCJOSHUA R. COOKBerkeley College ZSZachary SoneBerkeley College NBNUR BEDEIRBerkeley College

Key Points

The aim is to investigate the role of hyperinsulinemia in metabolic dysfunction by optimizing diazoxide treatment.
Conducted a randomized, double-blind pilot trial (NCT05729282) with adults having BMI 27-50 kg/m2 and insulin resistance.
Participants received either placebo, diazoxide 1 mg/kg, or diazoxide 2 mg/kg twice daily for 14 days to measure hepatic de novo lipogenesis.
Fasting blood samples were collected at baseline and after treatment to assess glucose, insulin, C-peptide, and lipid parameters.
2 mg/kg diazoxide significantly reduced fasting insulin by 37% from baseline (p=0.012), while fasting glucose increased by 17 mg/dL (p=0.07).
Hepatic de novo lipogenesis trended 47% lower in diazoxide-treated subjects and correlated with post-treatment insulin levels.

Abstract

Introduction and Objective: Hyperinsulinemia is generally regarded as a surrogate marker of insulin resistance, but high insulin levels may drive the development of metabolic dysfunction-associated steatotic liver disease (MASLD) by continuing to stimulate hepatic de novo lipogenesis (DNL) despite systemic insulin resistance. One strategy to understand the pathogenic role of hyperinsulinemia is to directly reduce high insulin levels in people with insulin resistance. Methods: We conducted a randomized, double-blind pilot Current; CorMedix. J. Wattacheril: Research Support; Current; Regeneron Pharmaceuticals Inc. Advisory Panel; Ended; AstraZeneca. Advisory Panel; Current; GlaxoSmithKline plc. Research Support; Ended; Galectin Therapeutics. H. Ginsberg: None. B. Laferrère: Consultant; Ended; Azurity. M.K. Hellerstein: Research Support; Current; Lilly, Merck & Co., Inc. Funding National Institutes of Health (K12DK133995, K23DK140614, UL1TR001873), Columbia University Department of Medicine, University of California Rausser College of Natural Resources

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