Hormonal
GLP-1/glucagon co-agonists achieve superior weight loss and metabolic improvements compared to GLP-1 mono-agonists by combining central appetite suppression with glucagon-mediated increases in energy expenditure and hepatic lipid oxidation.
GLP-1/glucagon co-agonists (like cotadutide and efinopegdutide) are emerging treatments that target both appetite and energy expenditure. They appear to offer greater weight loss than current GLP-1-only drugs (like semaglutide or liraglutide) and may also improve liver health. However, they carry a higher risk of gastrointestinal side effects like nausea and vomiting. Patients should expect a careful dose-titration process to manage these effects.
The combination of GLP-1 and glucagon administration in rodents has been shown to increase c-Fos expression in appetite regulating centres and polypharmacy with these hormones leads to a synergistic effect on food intake reduction over single hormone administration... Overall, these physiological studies support the notion that GLP-1 and glucagon possess dose-dependent synergism, leading to enhanced suppression of food intake, plus increased resting energy expenditure.
Why this rating
Supported by multiple pre-clinical and Phase 2 clinical trials, though long-term Phase 3 data is still emerging.
Source
Striking the Balance: GLP-1/Glucagon Co-Agonism as a Treatment Strategy for Obesity
David C. D. Hope et al. · Frontiers in Endocrinology · 2021
DOI 10.3389/fendo.2021.735019
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