The field of weight-loss drug development in 2024 witnessed a spectacle reminiscent of "the noblemen of the Five Mausoleums, in their silken robes and fine steeds, disregarding their own opulence." Developers, both large and small, ventured into this domain brimming with boundless opportunities, each striving to outdo the other, creating ripples that set off waves of innovation. Following the dominance of semaglutide and tirzepatide, what challenges and opportunities will the development of weight-loss drugs face in 2025?
1. Potential Efficacy of Weight-loss Drugs in Organ Protection
GLP-1 receptor agonist drugs were originally developed to help diabetic patients control their blood glucose levels. However, more and more research has revealed their benefits to health in other areas, particularly in organ protection. Generally, GLP-1 drugs promote insulin secretion, assisting diabetic patients in maintaining normal blood glucose levels. Yet, even individuals without diabetes, such as those with heart disease who are overweight, can benefit from these drugs. For instance, the SELECT research found that individuals using semaglutide not only had a reduced risk of dying from cardiovascular disease but also experienced a decreased likelihood of heart attacks and strokes.
This has led scientists to ponder whether GLP-1 improves health not solely through weight loss but also through direct organ protection. To elucidate this matter, more research is needed, especially among individuals without diabetes and with normal weight, to understand how these drugs work.
Currently, we are not entirely certain whether the organ-protective effects of GLP-1 drugs are a result of the drugs themselves or a consequence of the health improvements brought about by weight loss. Clarifying this issue will help doctors better utilize these drugs, not only for diabetic patients but also potentially bringing health benefits to other populations.
Can GLP-1 Drugs Manage Neurodegenerative Diseases
GLP-1 drugs not only aid in weight loss but also alleviate inflammation, which partly explains their potential to slow down neurodegenerative diseases. Both Parkinson's disease and Alzheimer's disease are associated with inflammation in the brain.
In a small clinical trial, the GLP-1 drug exenatide improved symptoms in patients with moderate Parkinson's disease. In another small-scale experiment, liraglutide slowed the rate of cognitive decline in patients with mild Alzheimer's disease by 18% over a year.
Some researchers believe that GLP-1 drugs have the potential to cross the blood-brain barrier. If this is indeed the case, the effectiveness of these drugs in treating neurodegenerative diseases could be significantly enhanced. However, it is still unclear to what extent these drugs enter the brain, and animal research has shown differences among GLP-1 drugs in this regard. For example, exenatide appears to cross the blood-brain barrier, and Christian Hölscher, a neuroscientist at the Henan Academy of Innovations in Medical Science in Zhengzhou, China, attributes the initial success of exenatide in treating Parkinson's disease to its ability to cross the blood-brain barrier. Hölscher points out that a modified exenatide analogue with a larger molecular weight lost its ability to cross the blood-brain barrier and, consequently, its ability to manage Alzheimer's disease, indicating the importance of delivering GLP-1 drugs into the brain for treating neurodegenerative diseases. Hölscher also notes that semaglutide lacks the potency to cross the blood-brain barrier, so its ability to improve cognitive decline in Alzheimer's disease patients may not be as good.
There are differing opinions on this viewpoint. Some argue that current data are insufficient to establish a correlation between the drug's ability to cross the blood-brain barrier and its effectiveness in treating neurodegenerative diseases. Regardless, the potential of GLP-1 drugs in managing Alzheimer's disease and Parkinson's disease is one of the key fields of focus for the pharmaceutical industry in the future.
Can GLP-1 Drugs Manage Kidney Disease
GLP-1 drugs also offer hope for chronic kidney disease, which affects over 10% of the global population. In particular, chronic kidney disease is considered "one of the world's largest untreated public health...
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