This hypoglycemic drug has an amazing oral technology! Can people who want to lose weight take it?

In the past few years, those who want to lose weight may have heard of the name "semaglutide". With the two major labels of only one injection a week and rapid weight loss, it quickly became a phenomenal product in the entire medical field. Even Musk has promoted it. A netizen asked Musk on Twitter what his secret to losing weight was. Musk replied: fasting, and Wegovy (semaglutide injection for weight loss), which helped me lose 18 pounds in a month.

Because of its great reputation for weight loss, everyone has overlooked that it is actually a hypoglycemic drug, not a weight loss drug. At least in China, semaglutide is only approved for type 2 diabetes and has not yet been approved for weight loss.

As a hypoglycemic drug, semaglutide has many advantages. In addition to lowering blood sugar, it also has cardiovascular protective effects, can reduce the risk of cardiovascular disease, reduce the mortality rate of cardiovascular disease, and has a clear weight loss effect.

Recently, semaglutide has received another blockbuster news. In January 2024, Novo Nordisk's semaglutide tablets (trade name: Novoxin) were approved for marketing by the National Medical Products Administration for the treatment of type 2 diabetes. This means that in the future, Chinese diabetic patients can take semaglutide orally!

The successful oral administration of the "miracle drug" semaglutide, what is the historical significance behind it? Compared with injections, what is the efficacy and safety of semaglutide oral preparations? Can Chinese patients afford it? Can it be used for weight loss? This issue of "Eye Health for Reality" will reveal the secrets!

1. Semaglutide has been changed from injection to oral administration. How amazing is this technology?

Semaglutide has always been administered by injection. It looks like a pen, and you need to install a needle, exhaust the air, adjust the dosage scale, disinfect the injection site, and then inject it. During the injection process, many novices will first prepare themselves mentally, "I was trembling with fear when the injection went in, and it was a little painful," a diabetic who tried the injection for the first time recorded on social media.

The injection of semaglutide requires certain operating skills, causes trauma during administration, and requires a cold chain throughout the process, which affects patient compliance. Therefore, researchers have been hoping to find a more convenient way of administration, such as oral administration.

However, there is always a huge gap between ideal and reality. Semaglutide belongs to the GLP-1RA class of drugs, and achieving oral administration has always been a difficult problem in the development of drug preparations. The reason is that, like insulin, semaglutide belongs to the class of polypeptide substances. If it is taken orally, it will be destroyed by gastric acid and proteases in the digestive tract before it is absorbed by the gastrointestinal tract.

In 2019, the US FDA approved the marketing of semaglutide tablets, which means that the world's first oral GLP-1RA drug was approved, which is a milestone. It should be noted that since the discovery of insulin in 1921, there has been no oral insulin product in the world.

Novo Nordisk scientists innovatively used the "SNAC absorption enhancer" to increase the bioavailability of oral semaglutide molecules by about 100 times.

The full name of SNAC is (sodium N-[(2-hydroxybenzoyl)amino])octanoate), which is an intestinal permeation enhancer that can adhere to the gastric mucosa together with polypeptides, thereby promoting gastric mucosal absorption. When the tablet successfully enters the stomach and disintegrates, SNAC increases the local pH in the stomach through buffering, neutralizes the acidity of local gastric acid, and reduces the degradation of semaglutide by pepsin. Next, SNAC binds to the lipid membrane of gastric cells, promoting the rapid absorption of semaglutide across the cell membrane into the blood. Simply put, the drug has been absorbed before it has time to be broken down.

Zhou Yebin, a pharmaceutical industry practitioner and a PhD in genetics from the University of Alabama, once wrote that this is something that "seems simple, but is actually very difficult to achieve." Most importantly, this innovative technology lays the foundation for all future peptide drugs. It is foreseeable that various oral insulins will be launched one after another in the future.

2. Is there any difference in efficacy and safety between semaglutide tablets and injections?

Since it is the world's first oral GLP-1RA drug on the market, will the effect of semaglutide tablets be inferior to that of injected liquid?

In this regard, Novo Nordisk's PIONEER series of clinical studies have provided results: oral semaglutide not only retains the effectiveness and safety of injections, but also eliminates the compliance issues associated with injections.

In terms of effectiveness, the dose-effect curves of the two formulations of semaglutide are basically the same. Both preparations can significantly reduce HbA1c levels, significantly improving the HbA1c compliance rate by up to 80%. In terms of safety, the most common adverse reactions of both preparations are gastrointestinal reactions, with mild to moderate nausea being the most common, which gradually decreases over time, and the incidence of serious adverse events is similar to that of the control group.

In other words, in terms of clinical efficacy and safety, the two dosage forms of semaglutide are "equally matched" and can both achieve effective and safe blood sugar lowering.

Currently, the most significant difference between the two dosage forms is the frequency of use. The injection is administered once a week, while the tablet is taken every day. In addition, oral tablets do not require cold chain storage and transportation, which makes them more convenient for patients to take.

3. Is the price expensive? Is it affordable for the general public?

The extent to which semaglutide tablets are accepted by the public also depends on a key factor: price.

Let's first look at the price of semaglutide injection. At present, there are two main specifications of semaglutide injection in China, 1.5ml or 3ml, both of which are 1.34mg/ml. On e-commerce platforms, the price of 1.5ml is about 700 yuan, and the price of 3ml is about 850 yuan. The price of semaglutide (3ml) in public hospitals is even lower, about 716 yuan per vial.

The dosage of semaglutide injection is 0.25mg~1mg each time, once a week, and the monthly usage is about 1-4mg. If you buy 3ml semaglutide injection, the monthly price is about 180-850 yuan. In addition, the injection form has entered Class B medical insurance, and 50%-80% of the cost can be reimbursed. If there is medical insurance that can reimburse, the monthly use of semaglutide is about 53.7-214 yuan, and the patient's burden is lighter.

At present, the price of semaglutide tablets in China has not been announced. According to the countries where it has been launched, the highest price is in Europe and the United States. The price of semaglutide tablets (30 tablets) of different doses (3 mg/7 mg/14 mg) is US$935.77, which is about RMB 223.9 per tablet. The cheapest price is in Japan, where they are priced according to the dose, with the lowest 3 mg dose at 6.8 yuan per tablet and the highest 14 mg dose at 23.7 yuan per tablet.

If my country's pricing is calculated based on the price of Japanese semaglutide tablets, the monthly price for users is approximately 200-700 yuan, which is basically the same as the price of domestic injections.

There are many factors that determine the price of semaglutide tablets when they enter the Chinese market. Industry experts said that the initial price of oral tablets may be high, and it is still unclear whether they can be included in medical insurance.

If it can really enter the market at a lower price, it will undoubtedly benefit many diabetic patients.

4. Can the newly launched semaglutide tablets be used for weight loss?

After semaglutide tablets were launched on the market, I believe that many people who want to lose weight will set their sights on this "oral hypoglycemic drug". Even in China, many people have taken semaglutide tablets through purchasing agents. On a certain social software, a user shared his experience of taking the "Japanese version of oral semaglutide" purchased through a purchasing agent, "Although I lost weight, the side effects are very serious", "Nausea, vomiting, diarrhea, and lost 3 kilograms in a week."

(On social media, netizens discussed their experience of taking semaglutide orally for weight loss)

It must be emphasized that the weight loss indication of semaglutide tablets is still in the Phase III clinical stage, and has not yet been approved for weight loss in any country or region. The oral semaglutide tablets approved in my country do not include weight loss in their indications.

Even for semaglutide injection, which is indicated for weight loss, the US FDA has strictly limited its indication for weight loss: it is suitable for adults with a body mass index (BMI) ≥ 30kg/㎡; and for overweight adults with at least one weight-related disease (such as hypertension, type 2 diabetes, high cholesterol) with a BMI ≥ 27kg/㎡. Off-label use will not only bring no benefits, but will expose you to risks, so do not use it blindly.

Based on the various abuses and off-label uses of semaglutide injection in the field of weight loss, it can be inferred that there will be some chaos in the use of semaglutide tablets after they are launched. Behind these chaos, there is the pursuit of profit and the pursuit of beauty. However, only reasonable use can make the new drug play its greatest advantage and let every patient truly benefit.

【References】

【1】Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019Apr 12;10:155. doi: 10.3389/fendo.2019.00155.

【2】Kalra S, Sahay R. A Review on Semaglutide:An Oral Glucagon-Like Peptide 1 Receptor Agonist in Management of Type 2Diabetes Mellitus. Diabetes Ther. 2020 Sep;11(9):1965-1982. doi:10.1007/s13300-020-00894-y.

【3】Wilding JPH, Batterham RL, Calanna S, etal. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med.Mar 18 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183

【4】Aroda, VR, et al.PIONEER 1:Randomized Clinical Trial of the Efficacy and Safety of Oral SemaglutideMonotherapy in Comparison With Placebo in Patients With Type 2 Diabetes.Diabetes Care, 2019. 42(9): p. 1724-1732.

【5】Rodbard, HW, et al. OralSemaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care, 2019. 42(12): p. 2272-2281.

【6】Rosenstock, J., et al. Effect ofAdditional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in AdultsWith Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea:The PIONEER 3 Randomized Clinical Trial. JAMA, 2019. 321(15): p. 1466-1480.

【7】Pratley, R., et al. Oral semaglutideversus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): arandomised, double-blind, phase 3a trial. Lancet, 2019. 394(10192): p. 39-50.

【8】Mosenzon, O., et al.Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renalimpairment (PIONEER 5): a placebo-controlled, randomized, phase 3a trial. Lancet Diabetes Endocrinol, 2019. 7(7): p. 515-527.

【9】Husain, M., et al. Oral Semaglutideand Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med, 2019.381(9): p. 841-851.

【10】Pieber, TR, et al. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin intype 2 diabetes (PIONEER 7): a multicentre, open-label, randomized, phase 3atrial. Lancet Diabetes Endocrinol, 2019. 7(7): p. 528-539.

【11】Zinman, B., et al.Efficacy, Safety,and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With orWithout Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial.Diabetes Care, 2019. 42(12): p. 2262-2271.

【12】Oral version of semaglutide is launched in China for the treatment of diabetes, with formulation innovation enabling oral administration https://www.thepaper.cn/newsDetail_forward_26193699

【13】Semaglutide tablets approved in China, with the highest price in Europe and the United States and the lowest in Japan
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