ABSTRACT
OBJECTIVE To comprehensively evaluate four weekly preparations of glucagon-like peptide-1 receptor agonist （GLP-1RA） marketed in China，and to provide evidence for hospitals to optimize drug catalogs and clinical rational drug use. METHODS Mini health technology assessment method was used to establish detailed evaluation rules according to A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions， and conduct comprehensive evaluation of four GLP- 1RA weekly preparations from aspects of pharmaceutical characteristics， effectiveness， safety， economy and other attributes. RESULTS Mini health technology assessment scores of the four GLP-1RA weekly preparations from high to low were dulaglutide 78.60 points， semaglutide 77.35 points，polyethylene glycol loxenatide 67.40 points， and exenatide microspheres 65.50 points， respectively. Dulaglutide had advantages in reducing blood sugar， arteriosclerotic cardiovascular disease， kidney benefits， and cost- effectiveness. Semaglutide had advantages in reducing blood sugar and weight loss， but its cost-effectiveness was lower than that of dulaglutide. Exenatide microspheres had advantages in the use of children， but its daily average treatment cost is the highest. Polyethylene glycol loxenatide needed further clinical evidence. CONCLUSIONS Four GLP-1RA weekly preparations all have high pharmaceutical comprehensive scores. Dulaglutide and semaglutide may have more comprehensive pharmaceutical value among them， while the use of exenatide microspheres for children is unique.
ABSTRACT
Clinical therapies for chronic pain are limited. While targeted drugs are promising therapies for chronic pain, they exhibit insufficient efficacy and poor targeting. The occurrence of chronic pain partly results from central changes caused by alterations in neurons in the rostral ventromedial medulla (RVM) in the brainstem regulatory pathway. The RVM, which plays a key role in the descending pain control pathway, greatly contributes to the development and maintenance of pain. However, the exact roles of the RVM in chronic pain remain unclear, making it difficult to develop new drugs targeting the RVM and related pathways. Here, we first discuss the roles of the RVM and related circuits in chronic pain. Then, we analyze synaptic transmission between RVM neurons and spinal cord neurons, specifically focusing on the release of neurotransmitters, to explore the cellular mechanisms by which the RVM regulates chronic pain. Finally, we propose some ideas for the development of drugs targeting the RVM.
