Hormonal
Targeting the melanocortin-4 receptor (MC4R) with biased agonists that favor Gq/11 signaling over Gs signaling reduces food intake and adiposity without causing adverse cardiovascular effects like hypertension and tachycardia.
If you have a specific genetic form of obesity linked to MC4R, a drug called setmelanotide may help you lose weight and improve glucose tolerance without raising your blood pressure, unlike some older treatments. This is because it targets the specific receptor pathway that controls appetite without triggering the heart-related side effects.
As such, ligands that bias MC4R signalling to favour Gq/11 should suppress appetite while avoiding cardiovascular effects. Setmelanotide is the first approved anti-obesity drug... Setmelanotide decreased food intake and adiposity, improved glucose tolerance and was associated with persistent weight loss in non-human primates, without effect on blood pressure and heart rate... In vitro studies have indicated that setmelanotide is more efficacious in Gq/11-PLC activation than Gs-activation, which may explain why the drug is not associated with adverse effects on blood pressure observed with other MC4R agonists
Why this rating
The claim is supported by pre-clinical models (non-human primates) and in vitro studies, with mention of clinical trials in humans with MC4R mutations, but lacks large-scale general population trial data in this specific review.
Source
RISING STARS: Targeting G protein-coupled receptors to regulate energy homeostasis
Aqfan Jamaluddin et al. · Journal of Molecular Endocrinology · 2023
DOI 10.1530/jme-23-0014
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 →