Hormonal
Triple agonists targeting GLP-1, GIP, and Glucagon receptors (GCGR) offer additional metabolic benefits, including increased energy expenditure and weight loss, by combining the insulinotropic effects of incretins with the lipolytic and anorectic effects of glucagon.
For patients with Type 2 Diabetes and obesity who need more than standard treatment, triple-agonist medications (targeting GLP-1, GIP, and Glucagon) are in early development. These drugs aim to boost weight loss and energy expenditure by leveraging the body's natural hormonal responses to food. Because they are still in early trials, their long-term safety and optimal dosing are not yet fully established, but they represent a promising next step for complex metabolic cases.
In addition, simultaneously engaging GLP-1, GIP, and GCG receptors... The rationale for GLP-1/glucagon co-agonism is to achieve weight loss in combination with good glycemic control and energy equilibrium, as glucagon induces energy expenditure, increases lipid metabolism, and inhibits food intake.
Why this rating
The paper states these molecules are in 'early-stage clinical trials' and that 'whether additional synergistic or antagonistic interactions... is not known,' indicating lower certainty regarding chronic efficacy and safety compared to established drugs.
Source
Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets
Franco Folli et al. · American Journal of Physiology-Endocrinology and Metabolism · 2023
DOI 10.1152/ajpendo.00236.2023
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