PPAR Agonist and GLP-1 Combination Therapy for Dose Reduction
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Solution Overview
Problem
Existing GLP-1 receptor agonists, such as semaglutide and liraglutide, are associated with adverse effects like nausea, vomiting, diarrhea, abdominal pain, and constipation, and there is a need to enhance their therapeutic effect and reduce these side effects.
Innovation Solution
Combining a PPAR agonist, such as elafibranor, with a GLP-1 receptor agonist to achieve a synergistic action on steatosis, insulin levels, glycemia, and body weight regulation, allowing for reduced dosages of the GLP-1 receptor agonist and minimizing adverse effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If GLP-1 receptor agonists are administered at higher doses to improve therapeutic effect, then glycemic control and body weight regulation are enhanced, but gastro-intestinal adverse effects such as nausea, vomiting, diarrhea, abdominal pain and constipation increase
Solution Approach 1:
The patent combines a GLP-1 receptor agonist with a PPAR agonist (elafibranor) into a single therapeutic regimen. This combination allows the PPAR agonist to enhance the metabolic effects of the GLP-1 agonist while enabling dose reduction of the GLP-1 agonist, thereby improving glycemic control and body weight regulation with fewer gastro-intestinal side effects.
Solution Approach 2:
The PPAR agonist acts as an intermediary that potentiates the therapeutic effects of the GLP-1 receptor agonist. By introducing this intermediate agent, the patent achieves enhanced glycemic control and body weight regulation at lower doses of the GLP-1 agonist, reducing the direct exposure of the gastrointestinal system to high doses of the GLP-1 agonist and thereby minimizing adverse effects.
2Object-affected harmful factors
If GLP-1 receptor agonist dosage is reduced to minimize adverse effects, then gastro-intestinal side effects are reduced, but therapeutic effect on glycemia and body weight regulation diminishes
Solution Approach 1:
The patent merges the actions of a GLP-1 receptor agonist and a PPAR agonist into a combined therapy. The PPAR agonist component compensates for the reduced therapeutic effect of the lower-dose GLP-1 agonist, maintaining glycemic control and body weight regulation efficacy while allowing the GLP-1 agonist to be administered at tolerable doses that minimize gastro-intestinal adverse effects.
Solution Approach 2:
The patent changes the dosing parameters of the GLP-1 receptor agonist by administering it at reduced doses when combined with a PPAR agonist. This parameter change is made possible because the PPAR agonist contributes additional therapeutic mechanism, thereby maintaining overall therapeutic effect despite the reduced dose of the GLP-1 agonist and minimizing adverse effects.
3Object-affected harmful factors
If combination therapy with PPAR agonist and GLP-1 receptor agonist is used to reduce GLP-1 receptor agonist dosage, then adverse effects are reduced and synergistic action on steatosis and insulin levels is achieved, but treatment complexity increases
Solution Approach 1:
The patent combines two drugs with complementary mechanisms of action into a single therapeutic regimen. This merging allows for dose reduction of the GLP-1 receptor agonist and achieves synergistic effects on multiple parameters including steatosis, insulin levels, and glycemia, while the coordinated action of the two agents simplifies the overall treatment strategy compared to using higher doses of GLP-1 agonist alone.
Data Source
AI summary
The present invention relates to a combination therapy comprising a PPAR agonist, such as elafibranor, and a GLP-1 receptor agonist, such as semaglutide, liraglutide, exenatide, lixisenatide, albiglutide and dulaglutide, for the treatment of a condition is selected from the group consisting of non-alcoholic fatty liver disease, diabetes and obesity.