​Survodutide, also known as BI 456906, is an investigational peptide that functions as a dual agonist for the glucagon and glucagon-like peptide-1 (GLP-1) receptors. This dual activation aims to enhance energy expenditure and reduce food intake, thereby addressing conditions such as obesity and metabolic dysfunction-associated steatohepatitis (MASH). ​pubmed.ncbi.nlm.nih.gov+8zealandpharma.com+8pubmed.ncbi.nlm.nih.gov+8

Mechanism of Action

By simultaneously targeting the glucagon and GLP-1 receptors, survodutide is designed to:​

• Increase Energy Expenditure: Activation of the glucagon receptor can elevate metabolic rate, promoting the utilization of stored energy.​
• Reduce Food Intake: Stimulation of the GLP-1 receptor contributes to appetite suppression, leading to decreased caloric consumption.​

This combined mechanism supports significant weight loss and improved metabolic health. ​pubmed.ncbi.nlm.nih.gov+3medchemexpress.com+3dom-pubs.onlinelibrary.wiley.com+3

Clinical Development

Survodutide is currently undergoing Phase 3 clinical trials to evaluate its efficacy and safety in individuals with overweight and obesity, including key sub-populations. These studies, known as SYNCHRONIZE-1 and SYNCHRONIZE-2, focus on participants with comorbidities, both with and without type 2 diabetes. Additionally, the SYNCHRONIZE-CVOT trial includes individuals with cardiovascular disease, chronic kidney disease, or risk factors for cardiovascular disease. ​zealandpharma.com+1pubmed.ncbi.nlm.nih.gov+1

Regulatory Status

The U.S. Food and Drug Administration (FDA) has granted survodutide both Fast Track Designation and Breakthrough Therapy Designation for the treatment of MASH with fibrosis. Similarly, the European Medicines Agency (EMA) has provided access to the Priority Medicine (PRIME) Scheme for the same indication. ​zealandpharma.com

Structural Characteristics

Survodutide is a 29-amino-acid acylated peptide that includes a C18 fatty acid chain. This structural modification enhances its pharmacokinetic properties, allowing for once-weekly subcutaneous administration. ​medchemexpress.com+1guidetopharmacology.org+1zealandpharma.com+1pubmed.ncbi.nlm.nih.gov+1

Research Highlights

• Obesity Treatment: In a randomized, double-blind, placebo-controlled Phase 2 trial, survodutide demonstrated significant weight loss in adults with obesity. ​pubmed.ncbi.nlm.nih.gov+2pubmed.ncbi.nlm.nih.gov+2zealandpharma.com+2
• MASH Therapy: Survodutide improved liver histology in individuals with MASH and fibrosis, indicating potential benefits in liver-related conditions. ​zealandpharma.com+1pubmed.ncbi.nlm.nih.gov+1
• Blood Pressure Reduction: Post hoc analyses from clinical trials have shown that survodutide may contribute to lowering blood pressure in adults with obesity. ​pubmed.ncbi.nlm.nih.gov

Conclusion

Survodutide represents a promising therapeutic candidate targeting both obesity and metabolic liver diseases. Its dual receptor agonism offers a multifaceted approach to weight management and metabolic health, with ongoing Phase 3 trials expected to provide further insights into its clinical utility.