What question did this study set out to answer?

This study aims to evaluate the efficacy and quality of weight loss achieved with RV-8451 in diet-induced obese nonhuman primates.

June 7, 2026

1104-OR: Muscle-Preserving Weight Loss with RV-8451, a Novel, Oral Nonpeptide GLP-1 Receptor Agonist, in Diet-Induced Obese Nonhuman Primates

Key Points

This study aims to evaluate the efficacy and quality of weight loss achieved with RV-8451 in diet-induced obese nonhuman primates.
DIO NHPs received RV-8451 for 18 days following a 7-day vehicle acclimation period.
Daily assessments were made of food and water intake and body weight, with body composition assessed via Dual-energy X-ray absorptiometry on day 19.
NHPs were fed a standard diet in the morning and high-fat fruit in the afternoon.
RV-8451 led to a 9% reduction in overall body weight after 19 days.
Fat mass reduced by up to 20% with no change in lean mass, while daily food intake decreased by approximately 65%.
Improvements in metabolic biomarkers included lower plasma ALT, triglycerides, and total cholesterol with no gastrointestinal adverse events observed.

Abstract

Introduction and Objective: GLP1R agonists (GLP1RAs) are effective treatments for obesity, but have limitations, including tolerability and loss of lean mass. RV-8451 is a first-in-class, oral non-peptide GLP1RA that produces substantial weight and fat mass loss while preserving lean mass in preclinical obesity models in rodents. This study assessed the efficacy and quality of weight loss (WL) with RV-8451 in diet-induced obese (DIO) non-human primates (NHPs). Methods: DIO NHPs were treated with RV-8451 for 18 days following a 7-day vehicle acclimation period. NHPs received a standard diet in the morning and fruit plus high-fat diet in the afternoon. Food and water intake and body weight were assessed daily, and body composition was quantified by Dual-energy X-ray absorptiometry on day 19. Results: RV-8451 was shown to be a potent agonist of human and monkey GLP1R. In DIO NHPs, RV-8451 reduced daily food intake by approximately 65% from baseline on average without altering water intake. After 19 days, RV-8451 produced 9% WL and up to 20% reduction in fat mass, with no change in lean mass. RV-8451 also improved clinical chemistry, lowering plasma alanine transaminase (ALT), triglycerides, and total cholesterol. No gastrointestinal (GI) adverse events (AEs) were observed. Conclusion: RV-8451, a first-in-class, muscle-preserving non-peptide GLP1RA, produced robust WL in obese NHPs driven by selective fat loss, preservation of lean mass, and improvements in metabolic biomarkers, with no GI AEs observed. These results in NHPs, together with rodent data, support RV-8451 as the first muscle-preserving GLP1RA to address key limitations of current GLP1RA therapies. RV-8451 has advanced into IND-enabling studies to support a planned Phase 1 clinical trial. Disclosure S. Collado: Employee; Current; Rivus Pharmaceuticals. H. Chobanian: None. A. Scott: None. B. Dalesandro: None. M. Luse: None. T.E. Richardson: None. C.A. Hamilton: None. S. Eaton: None. A. Cole: None. O.M. Khan: None. J. Dennis: Employee; Current; Rivus Pharmaceuticals. Stock/Shareholder; Current; Viking Therapeutics. A. Viacava Follis: Employee; Current; Rivus Pharmaceuticals. Employee; Ended; ROME Therapeutics. S.M. Khan: Employee; Current; Rivus Pharmaceuticals.

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1104-OR: Muscle-Preserving Weight Loss with RV-8451, a Novel, Oral Nonpeptide GLP-1 Receptor Agonist, in Diet-Induced Obese Nonhuman Primates

Key Points

Abstract

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