Recently, the indication of Semaglutide for long-term weight management has been approved in China, and Telaglutide has also just been approved. These are all drugs that act on the GLP-1 receptor. Over the past two years, Semaglutide has become popular worldwide for its significant weight loss effect, especially with the endorsement of celebrities such as Elon Musk, making it a new "internet celebrity." At the same time, various negative news related to Semaglutide has been repeatedly exposed. Is Semaglutide an angel or a devil? What is the mechanism of action of drugs targeting GLP-1? Let's talk about everything about Semaglutide in this issue.

Guests of this issue:

Yue Xiaotong: MD, physician in the Department of Dermatology and Aesthetics, The First Affiliated Hospital of Tsinghua University

Graduated from the PLA Medical College (301 Hospital) with a Doctor of Clinical Medicine and Master's degree, conducted research on stem cells, medical materials, and scars at the Military Medical Academy's Army Stem Cell and Regenerative Medicine Laboratory and the PLA General Hospital's Army Burn Research Institute. She is proficient in the combined application of photoelectricity, injection, and surgery for facial rejuvenation, body sculpting, skin aesthetics, and the treatment of chronic wounds.

Advertisement

Zhang Yuying: PhD, Director of Non-clinical Pharmacology of Zhipeptide Biopharmaceuticals

Zhipeptide Biopharmaceuticals was established in September 2018 and is a clinical development-stage bio-innovative drug company dedicated to developing innovative bio-drugs for the treatment of chronic metabolic diseases (such as diabetes, obesity, non-alcoholic fatty liver, etc.). Currently, there are 10 innovative recombinant protein drugs and biosimilar varieties under research and development in Zhipeptide Biopharmaceuticals' pipeline. One of them is an independent innovation international first-class innovative drug (ultra-long-acting GLP-1 receptor agonist ZT002 injection, which is expected to be injected only once a month) and a domestic substitute international blockbuster biosimilar drug (Semaglutide injection), which has entered the clinical trial stage at the end of 2022.Host:

Bing Ran: Master's degree from the Institute of Microbiology, Chinese Academy of Sciences

Timeline:

2:26

How much weight loss can semaglutide achieve

3:13

The reason why semaglutide has become the "star" of weight loss drugs

6:20Translate the following text into English: How to Transition from Diabetes Treatment to Weight Loss Indications

7:50

The reason why Semaglutide suppresses appetite

11:50

The biological mechanism of the GLP-1 target

24:39

How is the long-acting Semaglutide achieved

31:10

Are the "side effects" of Semaglutide really side effects?

51:13Is the combination of Semaglutide and Orlistat effective?

54:28

What other indications can be developed for GLP-1 receptor agonists?

1:00:25

Obesity needs to be taken more and more seriously.

1:04:55

Please use medication under the guidance of a doctor.

Content Focus

Semaglutide (a GLP-1 class of drugs) was initially developed as an adjunctive treatment for diabetes and has since gained attention for its significant weight loss effects. The uniqueness of this drug lies in its ability to directly act on the nervous system, activating specific neurons, thereby generating a sense of fullness and reducing food intake. Its weight loss effect has attracted widespread attention and research worldwide. Unlike similar drugs in the past, Semaglutide has become one of the most popular weight loss drugs on the market with its long-lasting effect and lower side effects. In addition, by adjusting dietary habits, increasing exercise, and combining with doctor's advice, users of Semaglutide can achieve more sustained and effective weight loss results. This podcast also discusses its long-term effects and potential risks, as well as research progress of other GLP-1 class drugs.● Mechanism of Action of GLP-1 Class Drugs

After eating, the rise in blood sugar stimulates the body to naturally produce GLP-1 receptor agonists. GLP-1 receptors are mainly distributed in the pancreas and the brain areas related to appetite regulation, thereby reducing the desire to eat and helping to control weight. However, due to the short half-life of endogenous hormones in the human body and their susceptibility to degradation, semaglutide is the first long-acting weekly medication of this kind. At the same time, Novo Nordisk has developed a new type of excipient that can protect GLP-1 from the destruction of digestive enzymes, making the oral administration of semaglutide possible, which is of great significance for improving patient compliance and quality of life.

Regarding the metabolic mechanisms of long-acting and short-acting GLP-1 analogs and their clinical applications in the treatment of obesity and diabetes, there are some differences. Short-acting drugs such as liraglutide require two daily injections to maintain effective concentrations. Long-acting semaglutide can significantly improve the stability and bioavailability of the drug by increasing the fatty acid chain in the drug molecule or connecting other modified fragments, thus achieving a long-acting effect.

● Drug Development and Clinical Application

In the process of drug development, the study of the mechanism of action of the drug is crucial, but it is often not fully understood before the drug is marketed. However, a large number of toxicological experiments need to be conducted to ensure its safety and avoid potential risks. After the drug is introduced to the clinic, from the initial observation of therapeutic effects to in-depth clinical application research, more indications are expected to be discovered, forming a positive cycle between research and development and clinical application. Therefore, scientific research and clinical practice complement and promote each other.● BMI Value and the Weight Loss Effect of Semaglutide

The higher the BMI, the better the weight loss effect, while the side effects are smaller and more tolerable. The currently approved semaglutide is a prescription drug, and the indication is for obese people with a BMI greater than or equal to 30 or between 27 and 30, and at least one weight-related comorbidity. Please use it under the guidance of a doctor.

● Side Effects of Semaglutide

The most common side effect of semaglutide is gastrointestinal reactions. In the brain area, the GLP-1 receptor also exists in the areas that control appetite and vomiting, so gastrointestinal reactions are often caused when using semaglutide. Rapid weight loss may lead to problems such as skin laxity, which is a common problem for all types of weight loss drugs. Therefore, it is necessary to cooperate with dermatological diagnosis and adopt necessary means to reduce such problems. Although there are reports that the use of semaglutide is associated with depressive symptoms, and studies suggest that it may be related to an eye disease that can lead to blindness, there is a lack of evidence-based medical evidence to support a causal relationship between the two, and further clinical research is needed to clarify the relationship.

Despite the large number of obese people, the actual number of people using drugs for weight loss is relatively small, while diabetic patients use this type of drug more commonly. Unlike the weight loss drugs that were quickly launched and quickly withdrawn in the past, due to the long-term application and widespread use of semaglutide, the possibility of similar problems occurring is relatively low.Future Development Opportunities for GLP-1 Class Drugs

New types of GLP-1 drugs are currently undergoing multiple related clinical trials, including exploration for diseases such as non-alcoholic fatty liver disease, Alzheimer's disease, improving female fertility rates, and treating polycystic ovary syndrome.