Introduction & Objective: Glucagon-like peptide receptor agonists (GLP-1RA) stimulate fibroblast growth factor (FGF-21) production and both have overlapping metabolic effects like glycemic control, suppression of food consumption, and body weight reduction. GL0034 has demonstrated excellent safety and tolerability in phase 1 trials. Further, a single dose of subcutaneous administration of GL0034 in individuals with obesity resulted in 3.3 kg of weight loss that was sustained till day 22
Methods: We explored a fixed dose (21nM/kg) of GL0034, semaglutide (Sema) and tirzepatide (TZP) given to db/db mice every third day for 4 weeks. Biomarkers were measured on days 14 and 28.
Results: GL0034 increased liver FGF-21 and, uncoupling protein-1 (UCP-1) in brown and white adipose tissues significantly more than Sema and similarly to TZP. The effects of GL0034 on HbA1c (↓), insulin (↑), glucagon (↓), weight loss (↑), triglycerides (↓), and cholesterol (↓) were similar to those induced by Sema and TZP. Food consumption was similar to TZP and lower than with Sema (Table).
Conclusion: In conclusion, GL0034 shows robust efficacy on multiple metabolic parameters and may serve as a promising new super GLP-1RA for individuals with obesity +/- type 2 diabetes and for the treatment of MASLD with enhanced therapeutic benefits partly due to increased liver FGF-21.
R. Thennati: None. V.S. Burade: None. M. Natarajan: None. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd. G.A. Rutter: Advisory Panel; Sun Pharmaceutical Industries Ltd. R.E. Pratley: Other Relationship; Bayer AG, Dompé, Endogenex, Inc., Gasherbrum Bio, Inc., Hengrui (USA) Ltd., Intas Pharmaceuticals Ltd., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sun Pharmaceutical Industries Ltd. Consultant; AbbVie Inc., AstraZeneca. Other Relationship; Bayer HealthCare Pharmaceuticals, Inc., Biomea Fusion, Carmot Therapeutics, Inc., Corcept Therapeutics, Fractyl Health, Inc., Genprex. Consultant; Getz Pharma. Other Relationship; Lilly USA LLC, Sanofi. Consultant; Scholar Rock, Inc. B. Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd. T. Vilsbøll: Consultant; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Mundipharma. Advisory Panel; Novo Nordisk, Lilly Diabetes, Sanofi. Speaker's Bureau; Bayer Inc., Gilead Sciences, Inc. Advisory Panel; Sun Pharmaceutical Industries Ltd. Research Support; Lilly Diabetes.
