117-OR: Effects of Triple-Hormone Receptor Agonist Retatrutide on Lipid Profiling in Participants with Obesity

• DOI: 10.2337/db24-117-or
• Publication Date: 2024-06-14T05:37:07Z
• Authors: VALENTINA PIRRO; MACKENZIE J. PEARSON; YANZHU LIN; MARK L. HARTMAN; KENNETH D. ROTH; KEVIN L. DUFFIN; JILL WILLENCY; AXEL HAUPT; GIACOMO RUOTOLO
• Keywords: 03 medical and health sciences; 0302 clinical medicine

In phase 2 (n=338), retatrutide (RETA), an agonist of GIP, GLP-1 and glucagon receptors, reduced body weight, fasting glucose, triglycerides (TG), LDL VLDL cholesterol in participants with obesity. To understand changes energy metabolism, lipidomic profiling was conducted. Adult obesity (BMI ≥30 kg/m2), or overweight ≥ 27 kg/m2) a weight related comorbidity, were randomized to RETA 1, 4, 8, 12 mg PBO for 48 wk. Fasting plasma collected at baseline, 24 wk, used measure acylcarnitines complex lipid species using targeted mass spectrometry. Data analyzed mixed model repeated measures. An increase 3-hydroxybutyrate (3-HB) noted after accompanied by 3-hydroxybutyrylcarnitine (C4OH), acetylcarnitine-to-free carnitine ratio (C2/C0), medium-chain ACs. The decrease TGs wk bias towards short-chain saturated species. decreased total dihydroceramides (DhCers) −20.1%, p-value <0.001. ketone C2/C0 observed is suggestive adipose tissue lipolysis reliance on fat oxidation. Inverse DhCers which associate improved insulin sensitivity, hepatic steatosis systemic inflammation. Evaluation potential benefits cardiovascular events MASLD may merit further investigation. Disclosure V. Pirro: Employee; Eli Lilly Company. M.J. Pearson: Y. Lin: Stock/Shareholder; Company, Pfizer Inc., AstraZeneca. M.L. Hartman: K.D. Roth: K.L. Duffin: J. Willency: A. Haupt: Diabetes. G. Ruotolo: None. Funding Company