Weekly Pemvidutide Regimen for CV Risk and GI Tolerability
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Solution Overview
Problem
Current GLP-1R and GLP-1R/GCGR dual agonists for weight loss are associated with high rates of gastrointestinal side effects and require prolonged titration, while their effect on cardiovascular disease-related factors remains unclear, necessitating a convenient dosing regimen that effectively reduces CV risk factors without these side effects.
Innovation Solution
The use of pemvidutide, a dual GLP-1R and GCGR agonist, administered weekly in doses of 1.2-2.4 mg, to reduce body weight and normalize CV disease-related factors such as cholesterol, triglycerides, and LDL particle concentration, with a design that minimizes gastrointestinal side effects and achieves therapeutic levels without prolonged titration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If GLP-1R and GLP-1R/GCGR dual agonists are used for weight loss, then weight loss is achieved, but gastrointestinal side effects occur at high rates
Solution Approach 1:
The patent applies parameter changes by modifying the dosing regimen from daily to weekly administration and optimizing the dose range (1.2-2.4 mg weekly). This change in administration frequency and dosage parameters reduces gastrointestinal side effects while maintaining weight loss efficacy, as the weekly dosing allows the body to adapt without the cumulative gastrointestinal stress of daily dosing
2Quantity of substance
If GLP-1R and GLP-1R/GCGR dual agonists are used for weight loss, then weight loss is achieved, but prolonged titration is required
Solution Approach 1:
The patent implements preliminary action by pre-determining the optimal weekly dose range (1.2-2.4 mg) based on clinical trial data, allowing patients to start at or near the therapeutic dose without requiring prolonged titration. This eliminates the time-consuming gradual dose escalation typically needed with daily agonists, as the weekly dosing schedule inherently provides a more favorable pharmacokinetic profile
3Reliability
If conventional dosing regimens are used, then therapeutic levels are achieved, but prolonged titration is required to reduce side effects
Solution Approach 1:
The patent applies periodic action by switching from daily to weekly dosing intervals. This periodic administration pattern allows the drug to reach therapeutic levels more efficiently while providing sufficient time between doses for the body to clear metabolites and reduce accumulation in the gastrointestinal tract, thereby achieving therapeutic efficacy without the need for prolonged titration to manage side effects
4Quantity of substance
If GLP-1R/GCGR dual agonists are used, then weight loss and metabolic effects are enhanced, but the effect on cardiovascular disease-related factors remains unclear
Solution Approach 1:
The patent applies universality by designing the weekly dosing regimen to simultaneously address multiple objectives: weight loss, metabolic improvement, and cardiovascular risk factor reduction. The clinical trials demonstrated that this single dosing strategy achieves comprehensive health benefits including weight loss, improved lipid profiles, reduced blood pressure, and decreased cardiovascular events, making the treatment universally beneficial across multiple disease domains
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 cardiovascular disease/disorder and/or reducing risk factors thereof by inducing reduction of pathogenic serum lipid mediators in a human being, wherein the human may or may not have other comorbidities such as obesity and/or type 2 diabetes. The dual GLP-1R and GCGR agonist includes the peptide product of SEQ ID NO. 1 (pemvidutide).