GLP-1 Agonist Peptides for NAFLD With Fewer GI Side Effects

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Solution Overview

Problem

Existing GLP-1 receptor agonists for treating non-alcoholic fatty liver disease (NAFLD) are limited by gastrointestinal side effects, which hinder effective dosing and patient compliance.

Innovation Solution

Development of non-macrocyclic functionalized peptides with specific structures, acting as GLP-1 receptor agonists, to treat metabolic disorders and fatty liver diseases, including NAFLD, without the gastrointestinal side effects of traditional GLP-1 receptor agonists.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional GLP-1 receptor agonists are used to treat NAFLD, then treatment efficacy is achieved, but gastrointestinal side effects increase

Engineering Contradiction:

Improvetreatment efficacyVSAvoidgastrointestinal side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of GLP-1 receptor agonists by changing parameters such as replacing macrocyclic structures with non-macrocyclic functionalized peptides, adjusting molecular weight, and modifying functional groups. These parameter changes result in compounds that maintain GLP-1 receptor agonist activity while reducing gastrointestinal side effects, as demonstrated by the reduced nausea and vomiting compared to traditional agonists.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If higher doses of GLP-1 receptor agonists are administered to improve treatment efficacy, then treatment effectiveness increases, but gastrointestinal adverse events worsen

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidgastrointestinal adverse events

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent employs parameter changes by optimizing the molecular structure of GLP-1 receptor agonists, specifically using non-macrocyclic functionalized peptides with modified pharmacokinetic properties. This allows achieving effective treatment doses without proportionally increasing gastrointestinal adverse events, as the structural modifications improve the therapeutic index.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260028385A1Compositions and methods for the treatment of metabolic and liver disorders

Publication Date: 2026.01.29 VIKING THERAPEUTICS INC

AI summary

Disclosed herein are small molecule GLP-1 receptor agonist compounds, pharmaceutical compositions, and the use and preparation thereof.