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Eur J Pharmacol (2021) 898:173999

The clinical trials supporting GLP-1 medications didn't include antioxidant supplementation, and post-market real-world data hasn't identified oxidative stress as a limiting factor in treatment outcomes

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Complementary Appetite Regulation The combination produces effects exceeding either agent alone through several mechanisms: Dual pathway activation targeting both incretin and amylin systems simultaneously Overlapping brain region effects with enhanced signaling in appetite control centers Additive gastric emptying delay producing stronger and longer-lasting satiety Complementary insulin effects with amylin modulating postprandial glucose via delayed absorption Synergistic energy expenditure with potential effects on metabolic rate exceeding monotherapy Cardiovascular and Metabolic Effects Clinical trials have demonstrated effects beyond weight reduction: Blood pressure reduction with significant decreases in systolic blood pressure Lipid profile improvement with favorable changes in cholesterol and triglycerides Glycemic normalization with 88% of prediabetic participants returning to normal glucose tolerance Hemoglobin A1c reduction of up to 2.2 percentage points in type 2 diabetes patients Cardiovascular risk reduction though long-term outcomes studies are ongoing Key Mechanistic Insight: The synergy between GLP1 and cagrilintide likely results from their complementary actions on different but overlapping neural circuits controlling appetite