Hormonal
Combining GIPR agonism or antagonism with GLP-1 R agonism produces synergistic weight loss in preclinical models, whereas GIPR signaling is not required for this synergy in humans.
Combining GIP and GLP-1 hormones (as seen in drugs like tirzepatide) is more effective for weight loss than GLP-1 alone, likely because they work together synergistically. However, the exact way this works in humans is still debated, as animal studies do not perfectly predict human biology.
Multiple publications from various groups have reported synergy between GLP-1 R agonists and GIPR agonists where the observed weight loss seen by combining GLP-1 R agonists and GIPR agonists is greater than the sum of the weight loss produced by either agent alone... While it is clear that GIPR signaling is necessary for the additional benefits of GLP-1 R agonists/GIPR agonists or antagonists in preclinical models, this is more controversial in man.
Why this rating
Strong preclinical data exists, but human physiological studies contradict the mechanism.
Source
Design of novel therapeutics targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) to aid weight loss
Iona Davies et al. · Expert Opinion on Drug Discovery · 2023
DOI 10.1080/17460441.2023.2203911
More from this paper
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
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →