DrugTimes BD Project DT-084 | A GLP-1/GCG/GIP Triagonist for the Treatment of Obesity, Type 2 Diabetes, and Steatohepatitis

In recent years, dual- and triple-targeting agents acting on glucagon-like peptide-1 receptor (GLP-1R), glucagon receptor (GCGR), and glucose-dependent insulinotropic polypeptide receptor (GIPR) have emerged as promising therapeutic strategies. By simultaneously modulating these three key metabolic pathways, such agents enable synergistic regulation across multiple physiological systems, offering more comprehensive improvement in metabolic dysregulation. This multi-target approach demonstrates significant advantages in terms of enhanced efficacy and improved safety profiles, positioning it as a leading frontier in the development of next-generation therapies for metabolic disorders. Eli Lilly and Novo Nordisk, the two leading players in the GLP-1 field, are actively advancing their respective pipelines in the triple-agonist space, intensifying technological competition in this domain.

Eli Lilly’s Retatrutide is currently the most clinically advanced GLP-1/GCG/GIP triagonist. It is now in Phase III clinical development for indications including obesity, type 2 diabetes (T2D), secondary prevention of cardiovascular events, and obstructive sleep apnea. In a Phase II trial in patients with obesity, Retatrutide demonstrated superior weight loss outcomes compared to tirzepatide and semaglutide, achieving a mean weight reduction of 24.2% over 11 months—the most robust pharmacological weight loss observed to date. Notably, the weight loss effect had not yet plateaued at higher doses, suggesting that extended treatment duration may yield even greater reductions. Additionally, Retatrutide showed favorable effects on blood pressure, lipid profiles, and glycemic control.

Novo Nordisk is also advancing aggressively in this field. On March 24, 2025, Novo Nordisk entered into a global (ex-China) rights acquisition agreement with Federal Pharmaceutical for UBT251, a long-acting synthetic peptide GLP-1/GCG/GIP receptor triagonist, in a transaction valued at up to $2 billion. UBT251 enables once-weekly subcutaneous administration. Compared to existing GLP-1-based therapies, its key advantage lies in its prolonged pharmacokinetic profile, significantly enhancing patient convenience and adherence. The molecule exhibits high in vivo stability, enabling sustained release and maintenance of therapeutic concentrations, reduced clearance, and extended duration of action, thereby improving overall therapeutic efficacy.

From Lilly’s Retatrutide to Novo Nordisk’s UBT251, these agents are not only setting new benchmarks in glycemic control and weight management but also marking the definitive arrival of a “multi-target era” in the treatment of metabolic diseases. As clinical development progresses, GLP-1 receptor agonists continue to demonstrate immense therapeutic potential. According to Evaluate Pharma, the global market for GLP-1 receptor agonists is projected to exceed $150 billion by 2030. Within this rapidly evolving landscape, next-generation triple receptor agonists, with their superior efficacy in both glucose regulation and body weight reduction, are poised to become pivotal therapeutic options, offering patients more comprehensive and effective treatments.

Currently, the DrugTimes BD team is seeking potential partners for a novel GLP-1/GCG/GIP triagonist indicated for obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH).

Project Overview

• Project ID: DT-20250718-084
• Project Title: A GLP-1/GCG/GIP Triagonist for the Treatment of Obesity, Type 2 Diabetes, and Metabolic Dysfunction-Associated Steatohepatitis (MASH)
• Indications: Obesity, Type 2 Diabetes (T2D), and MASH
• Drug Class: Peptide-based therapeutic
• Targets: GLP-1R / GIPR / GCGR

Key Advantages:

• Optimized Receptor Bias: Demonstrates a rationally balanced and biased agonist activity profile across GLP-1R, GCGR, and GIPR, potentially conferring improved safety and tolerability.
• Superior Efficacy: In repeat-dose studies at equivalent dosing, demonstrates greater weight loss efficacy compared to Retatrutide in preclinical models.
• Extended Half-Life: In rat pharmacokinetic studies, exhibits a longer half-life than both semaglutide and tirzepatide, supporting once-weekly subcutaneous administration.
• Flexible Formulation Strategy: The molecule is a fatty acid side chain-modified peptide suitable for weekly injection, with potential for future development of an oral formulation.

Development Stage: Phase 1

Partnership Opportunity: Seeking out-of-licensing partners for global rights (excluding Greater China) for further clinical development and commercialization.

Contact us:

For any questions, please contact DrugTimes BD Team at BD@drugtimes.cn, please include Project ID in the subject. Many thanks!