GLPwatch
Obesity pharmacotherapy: incretin action in the central nervous system.
Trends Pharmacol Sci · 2023
Last updated 2026-05-28Recent trials show that tirzepatide, which targets both GLP-1 and GIP receptors, leads to more weight loss than drugs that only target GLP-1 receptors. However, it is unclear how these receptors in the brain contribute to weight loss, as both activating and blocking GIP receptors in the brain have been linked to reduced weight in animal studies. The review explores how these brain receptors may work and discusses newer drugs that target multiple receptors to help with weight loss.
AI summary of the abstract below.
| Journal | Trends Pharmacol Sci, 2023 |
|---|---|
| Citations | 31 |
| Relative citation ratio | 3.82 |
| NIH percentile | 89 |
| Molecules | — |
| Conditions studied | Obesity |
Abstract
The prevalence of obesity is rising, creating an urgent need for efficacious therapies. Recent clinical trials show that tirzepatide, a dual agonist of receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), yields more weight loss than selective GLP-1 receptor (GLP-1R) agonists. Incretin receptors in the central nervous system (CNS) may contribute to these effects. Yet exactly how each receptor regulates body weight from within the CNS is not clearly understood. It remains especially unclear how GIP receptor (GIPR) signalling contributes to the effects of tirzepatide because both stimulation and inhibition of CNS GIPRs yield weight loss in preclinical models. We summarise current knowledge on CNS incretin receptor pharmacology to provide insight into the potential mechanisms of action of dual GIPR/GLP-1R agonists, with tirzepatide as the exemplar. In addition, we discuss recent developments in incretin-based dual- and tri-agonism for inducing weight loss in obese individuals.
Verbatim abstract via PubMed 36462999 ↗