Hormonal
Triple-agonist GLP-1/GIP/Glucagon analogs (e.g., retatrutide) produce superior weight loss compared to dual or single agonists by synergistically activating multiple satiety and energy expenditure pathways.
Newer 'triple-agonist' weight loss medications target three different hormonal pathways (GLP-1, GIP, and Glucagon) instead of just one. Clinical trials show these can lead to over 20% body weight loss, which is significantly higher than older single-target drugs. These are currently experimental and not yet widely available for general use.
Emerging tri-hormonal agonists, such as retatrutide, also activate the glucagon receptor, increasing energy expenditure and hepatic lipolysis [25]. These combinations result in even greater weight loss than isolated agonists. Thus, retatrutide can reduce >20% of body weight in 48 weeks—an unprecedented level among anti-obesity pharmacological therapies [30]
Why this rating
Based on Phase II clinical trials (Eli Lilly, 2023) cited in the review; robust but not yet fully mature Phase III data for commercial availability.
Source
Therapeutic Peptides in Aesthetic, Metabolic and Endocrine Conditions: Effects, Safety, Clinical Applications, and Future Perspectives
Guilherme Renke et al. · International Journal of Molecular Sciences · 2026
DOI 10.3390/ijms27093890
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