Oral version of semaglutide approved for marketing! Is it not a "magic drug for weight loss"?

On January 26, Novo Nordisk's Semaglutide tablets were approved for marketing by the National Medical Products Administration (NMPA) for the treatment of type 2 diabetes. This is the first oral GLP-1 (glucagon-like peptide-1) receptor agonist approved for marketing in China.

▲National Medical Products Administration Government Service Portal

The newly approved oral semaglutide is marketed under the name "Novoxin". Semaglutide is well-known for its weight loss effect. There is a joke that whoever can lower blood sugar and lose weight can win the world. In the past year, when talking about the blood sugar lowering and weight loss market, there is one name that cannot be avoided, that is semaglutide, which is almost equated with the "magic weight loss drug". However, it should be emphasized that the indication for the drug approved in China this time is the treatment of type 2 diabetes, not weight loss treatment. But the enthusiasm of the market may be difficult to stop.

Previously, according to data from the National Drug Evaluation Center, Novo Nordisk's application for clinical trials of semaglutide tablets in China was approved as early as September 2022: as an adjunct to weight management for adult patients, used for reduced-calorie diet and increased physical activity, with an initial body mass index (BMI) ≥28 kg/m2 (obesity), or ≥24 kg/m2 and <28 kg/m2 (overweight) and accompanied by at least one weight-related comorbidity.

The approval for listing will undoubtedly drop a "blockbuster bomb" on the domestic weight loss market worth over 10 billion yuan. Because, previously, all the injection versions of semaglutide were imported through cold chain, which to a certain extent caused its supply shortage. However, semaglutide oral tablets have considerable advantages in transportation, storage, and user acceptance (no injections are required). Once the weight loss indication is approved, it will undoubtedly further raise the market ceiling.

▲Semaglutide oral tablets (Source: online shopping platform)

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, originally used to treat type 2 diabetes. In the past two years, it has been highly sought after by celebrities and the capital market due to its excellent weight loss effect. How does Semaglutide play a role in lowering blood sugar and reducing weight? Can it really help you lose weight without doing anything?

How does semaglutide work for weight loss?

The drug molecule semaglutide simulates a hormone naturally present in the human body, GLP-1, with which it has 94% sequence homology. GLP-1 is one of the many hormones released by the small intestine after people eat. It can promote the secretion of insulin when acting on the pancreas, slow down the emptying of the stomach when acting on the digestive tract, and produce a feeling of fullness when acting on the hypothalamus. Therefore, drugs that simulate GLP-1 (such as semaglutide) can activate the GLP-1 receptors in the human body, which can not only regulate blood sugar and treat diabetes, but also slow down digestion and suppress appetite. Not only that, semaglutide is more stable than GLP-1 in the human body and can work after being used once a week.

Can oral medications compete with injectable medications?

▲Semaglutide injection (Source: Visual China)

Previously, in February 2021, semaglutide injection was approved for marketing in my country. At present, domestic semaglutide dosage forms can be divided into two types: semaglutide injection and semaglutide tablets. The specifications of semaglutide injection are 2mg/1.5 mL (1.34mg/mL) and 4mg/3 mL (1.34mg/mL), which are injected once a week; the specifications of semaglutide tablets are 3mg, 7mg, and 14mg, which are taken orally once a day.

Currently in China, although semaglutide injection has not been approved for weight loss indications, it has become a trend for many people to buy it on their own for weight loss. After the oral version is launched on the market, it is almost certain that a similar situation will occur again.

However, in addition to the risk point that it has not been approved for weight loss indications, there is another major difficulty in using oral semaglutide for weight loss.

Looking at the specifications of the injection and oral formulations of semaglutide alone, it can be found that the dosage of the oral formulation is larger than that of the injection. This is because a larger dose is required for the oral formulation to achieve the same blood concentration as the injection formulation. The SUSTAIN series and PIONEER series studies found that 7mg and 14mg oral semaglutide tablets had similar blood concentrations to 0.5mg and 1.0mg subcutaneous injections of semaglutide, respectively.

However, if the oral dosage form of semaglutide is to achieve the same effect as the injection dosage form, it is not enough to simply increase the dosage. This is determined by the molecular structure of semaglutide. Semaglutide is a polypeptide molecule, and this type of molecular drug is susceptible to enzymatic degradation, low permeability, and is severely affected by the gastrointestinal environment during oral administration, resulting in low oral bioavailability.

There is no “magic bullet” for weight loss!

Compared with previous weight-loss drugs, "new internet celebrities" such as semaglutide have indeed performed impressively, but these drugs are not perfect either.

(Photo source: Visual China)

These drugs are not without side effects, and it is not realistic to want to "lose weight by lying down" comfortably. In clinical trials of semaglutide, about 20% to 45% of participants reported gastrointestinal discomfort such as nausea, vomiting, diarrhea, and constipation. These side effects are less common at low doses and usually do not last for a long time, so the drug is currently considered safe. However, it will take longer to follow up and observe what results people will get from long-term medication to maintain their weight.

It is unrealistic to hope that you can "keep losing weight" after using semaglutide. Studies have shown that after a period of medication, the weight loss effect of semaglutide will enter a plateau period. Follow-up studies of participants in clinical trials found that within six months to a year after stopping the drug, most people regained most of their pre-trial weight. It is worth noting that subjects who maintained a healthy diet and exercise after stopping the drug had relatively less weight rebound.

So, although drugs such as semaglutide can help reduce appetite, they cannot change people's original eating habits and lifestyles. If these drugs are stopped, appetite may return and weight may rebound. It is worth affirming that these drugs give many dieters the confidence to act, but they cannot "cure" obesity once and for all.

These emerging weight loss drugs that have attracted attention are not "magic drugs". Weight loss should not be a blind follow-up behavior, but a scientific process. Before using any drug, you should consult a professional doctor to understand your physical condition and adaptability, and follow the doctor's advice and use the drug reasonably. Only in this way can you truly improve your quality of life and health level.

Text/David Duan

References: Beijing Science and Technology News, Medical Valley, Interface News, The Paper, etc.