Research
Hormonal
Dual or triple agonists targeting GLP-1, GIP, and/or Glucagon receptors (GCGR) produce superior weight loss compared to selective GLP-1 receptor agonists alone.
Newer obesity medications that target multiple receptors (like GLP-1, GIP, and Glucagon) are more effective for weight loss than older single-target drugs. These include Tirzepatide and Retatrutide, which are approved or in advanced trials for obesity and diabetes.
GoodSupportsHIGH confidence
designing single peptides co-agonists at GLP-1R and GCGR may produce superior body weight benefits to GLP-1R agonism alone
Why this rating
Supported by phase 2 trials and preclinical data, with some phase 3 trials ongoing.
Source
G protein-coupled receptors and obesity
Alessandro Pocai · Frontiers in Endocrinology · 2023
DOI 10.3389/fendo.2023.1301017
narrative_reviewCited 9×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- GLP-1 receptor agonists (GLP-1RA) such as semaglutide and liraglutide produce significant weight loss (≥10%) and cardiovascular benefits in adults with obesity.Strong
- Rapid weight loss from GLP-1 and dual/triple agonists can lead to significant loss of lean muscle mass, necessitating strategies to preserve muscle.Good
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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