Hormonal
Dual (GLP-1/GIP) and Triple (GLP-1/GIP/Glucagon) receptor agonists offer superior weight loss and metabolic benefits compared to GLP-1 mono-agonism by leveraging complementary mechanisms.
Newer multi-agonists (dual/triple) like retatrutide show much higher weight loss (up to 24%) than older GLP-1 drugs. They work by hitting multiple metabolic targets at once, which may be necessary for patients who don't respond sufficiently to GLP-1 alone.
Tri-agonism is founded on the following approach: GLP-1 receptor agonism promotes weight, which glucagon receptor agonism enhances through supplementary mechanisms, while GLP-1 and GIP receptor agonism stimulates insulin secretion and protects against hyperglycaemic risk... phase 2 trial of triagonist retatrutide... reported a 24.2% average weight reduction
Why this rating
Based on phase 2 trials; phase 3 data for some agents (e.g., retatrutide liver outcomes) is less mature or not fully detailed in this review.
Source
Review Article: <scp>GLP</scp>‐1 Receptor Agonists and Glucagon/<scp>GIP</scp>/<scp>GLP</scp>‐1 Receptor Dual or Triple Agonists—Mechanism of Action and Emerging Therapeutic Landscape in <scp>MASLD</scp>
Maryam Zafer et al. · Alimentary Pharmacology & Therapeutics · 2025
DOI 10.1111/apt.70196
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