The birth of the "miracle drug" semaglutide for weight loss

Unexpected discovery in venom: birth of weight loss "miracle drug" semaglutide

The development of GLP-1 drugs has undergone an evolution from animal to human sources, from short acting to long-acting.

The discovery of enteropancreatin and the rise of GLP-1

In 1932, Belgian scientist Jean La

Barre discovered that hormones secreted by the gastrointestinal tract can stimulate the secretion of insulin and named it "enteropancreatin". With the advancement of blood hormone level measurement technology, researchers have found that glucose dependent insulinotropic polypeptide (GIP) is one of the important factors of enteropancreatin.

With the development of genetic technology, scientists have also discovered another type of intestinal insulinotropic agent - glucagon like peptide-1 (GLP-1). Research has shown that GLP-1 can effectively stimulate pancreatic insulin secretion at extremely low concentrations (only 1/100 of GIP).

In 1992, Dr. John En from the United States extracted the natural GLP-1 like peptide Exendin-4 from the salivary glands of American lizards, providing important clues for the development of GLP-1 receptor agonists (GLP-1 RAs).

In 2005, the first GLP-1RA drug, exenatide, was approved for sale in the United States, ushering in a new era of GLP-1RA drugs.

Surprisingly, many patients with diabetes who received exenatide treatment not only got remission, but also lost weight. Clinical studies have shown that obese women treated with exenatide experience an average weight loss of 2.49 kilograms in the short term, with 30% of patients experiencing a weight loss of over 5%.

Breakthrough in Extending GLP-1 Effect

The half-life of natural GLP-1 is extremely short, only 1 to 2 minutes, and it is easily degraded by dipeptidyl peptidase-4 (DPP-4). Therefore, scientists are working on developing drugs that can inhibit DPP-4, prolong the action time of GLP-1, and develop longer acting GLP-1 analogs.

In 2005, exenatide was approved as the first GLP-1 RA drug, but due to poor homology with human GLP-1 and significant side effects, it was not widely used.

New generation GLP-1RA drugs

In 2017, semaglutide was launched, which is further improved on the basis of liraglutide and can be injected once a week, showing significant effects in weight loss. A clinical study showed that obese patients using semaglutide lost an average of 15% of their weight. Another study also confirmed that smeglutide can help non diabetes obese adults lose about 15.3 kg (33.7 lb). In June 2021, the FDA approved its use for the treatment of common obese patients (trade name: Wegovy).

In 2019, polyethylene glycol Losenapeptide was launched, which uses PEGylation technology to slow down the elimination of drugs in the kidneys, thereby prolonging circulation time in the blood. It is injected once a week.

In the same year, the oral form of semaglutide was officially launched, becoming the only oral GLP-1 RA drug.

In 2022, Tirzepatide was launched, which is the world's first drug that simultaneously acts on GLP-1R and GIPR (gastric inhibitory peptide receptor). Clinical studies have shown that the weight loss effect of teriparatide is superior to that of semaglutide. The results of a Phase 3 clinical trial published in the New England Journal of Medicine in 2022 showed that tilpotide can help obese patients successfully lose 16% to 22.5% of their weight, while the weight loss effect of semaglutide is approximately 15%, and the side effects of the two are not significantly different. In November 2023, the FDA approved its use for the treatment of obese patients with at least one weight related complication.

Lilly is currently researching a new type of three target agonist - Retatrutide. Phase 2 clinical trials have shown that at the highest dose, 48 weeks of treatment can help patients lose 24.2% weight, breaking the world record for weight loss drugs.

However, as the patents of several GLP-1RA drugs are about to expire, the competition in the field of diabetes treatment is becoming increasingly fierce. The patent for Liraglutide has expired in China, while the patent for Smeaglutide will expire in 2026, which may bring more variables to the market for emerging drugs and generic drugs.