Dual GLP-1R GCGR Agonist Peptides for Weight Loss and Glucose Control
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Solution Overview
Problem
Current GLP-1R agonists for treating obesity and diabetes are associated with high rates of nausea, vomiting, and diarrhea, and require titration to achieve therapeutic doses, while lacking convenient dosing regimens and optimal weight loss efficacy.
Innovation Solution
Development of dual agonist peptides with balanced affinity for both GLP-1R and GCGR, such as ALT-801 (pemvidutide), which are administered weekly to reduce adverse events like nausea and diarrhea, and induce significant weight loss and liver fat reduction without titration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If GLP-1R agonists are used to treat obesity and diabetes, then blood glucose control is improved, but adverse events like nausea, vomiting, and diarrhea increase
Solution Approach 1:
The patent combines GLP-1R agonist activity with GCGR agonist activity in a single dual-agonist peptide molecule. This merging of two receptor agonist functions into one compound allows simultaneous activation of both pathways, achieving superior blood glucose control and weight loss while the balanced agonism profile helps mitigate gastrointestinal adverse events compared to GLP-1R monotherapy
Solution Approach 2:
The patent modifies the receptor affinity parameters of the dual-agonist peptide to achieve balanced agonism at both GLP-1R and GCGR. By carefully tuning the peptide sequence and structure, the invention creates a compound with comparable affinity and efficacy at both receptors, which changes the pharmacological profile from unbalanced (GLP-1R dominant) to balanced dual-agonism, thereby improving the benefit-risk ratio
2Reliability
If GLP-1R agonists are administered at approved doses, then blood glucose control is achieved, but weight loss is only modest
Solution Approach 1:
The dual-agonist peptide merges GLP-1R and GCGR activation in a single molecule, allowing simultaneous pursuit of both blood glucose control and significant weight loss. The GCGR component provides additional weight loss mechanisms through increased energy expenditure and reduced appetite, complementing the GLP-1R effects and achieving greater weight reduction than GLP-1R monotherapy at comparable glucose control levels
3Weight of moving object
If GLP-1R agonists are used for weight loss, then some weight reduction is achieved, but dosing requires titration and is inconvenient
Solution Approach 1:
The patent changes the pharmacokinetic parameters of the dual-agonist peptide to achieve convenient weekly dosing. By optimizing the peptide's half-life, absorption rate, and clearance characteristics, the invention enables once-weekly administration that maintains therapeutic levels without requiring gradual titration, thereby improving ease of operation while achieving significant weight loss
Data Source
AI summary
This disclosure relates to the once weekly dosing regimen of a dual GLP-1R and GCGR agonist, formulations, and methods of using the same for treatment of chronic weight management, obesity and/or blood glucose control, including but not limited to dual agonist peptide product of SEQ ID NO. 1.