On December 12, Blue Whale News reported (Reporter Tu Jun) that Tesla CEO Elon Musk, who has popularized GLP-1 weight-loss drugs, once again passionately spoke out on Social Media. On December 11 local time, Musk posted on platform X, stating that nothing can improve the health, lifespan, and quality of life of Americans better than very cheap GLP-1 drugs. He pointed out that most medical expenditures occur at the end of life, and obesity is often a significant factor leading to diseases; thus, popularizing GLP-1 drugs can save medical costs in the long run.

According to the 2024 World Obesity Map, 42% of adults worldwide (approximately 2.2 billion) were overweight or obese in 2020. This number is expected to reach 54% (3.3 billion) by 2035. Such astonishing data has also propelled GLP-1 receptor agonists, known as 'pain-free weight loss' drugs, into the limelight. Eli Lilly and Co and Novo-Nordisk A/S have always been regarded as the 'dual heroes' of weight-loss drugs in the industry.

Recently, Eli Lilly announced that its dual-target weight-loss drug tirzepatide has head-to-head defeated semaglutide in terms of weight loss. The rapid weight loss effect of tirzepatide seems to be superior; however, experts indicate that the competition in weight-loss drugs goes beyond just rapid weight loss, and breakthroughs are needed in safety and sustainability aspects, such as reducing weight rebound, minimizing muscle loss, increasing convenience of use, and decreasing side effects.

Did tirzepatide surpass semaglutide? Rapid weight loss has led to 'aesthetic fatigue'.

Eli Lilly and Co and Novo-Nordisk A/S have always been referred to as the 'dual heroes' of weight-loss drugs in the industry. Novo-Nordisk's semaglutide, as the company's second-generation blockbuster blood sugar-lowering weight-loss product, truly brought 'pain-free weight loss' into public awareness, with its injectable forms Ozempic and Wegovy respectively getting FDA approval in December 2017 and June 2021 for diabetes and weight loss indications.

However, about a year after Wegovy's launch, it faced its biggest competitor. In May 2022, the FDA approved Eli Lilly's flagship product tirzepatide Zepbound for the treatment of type 2 diabetes; in November 2023, Tirzepatide was approved by the FDA for chronic weight management. Unlike semaglutide, which is a single-target GLP-1RA drug, Tirzepatide is a dual agonist of GIP/GLP-1.

Recently, Eli Lilly announced the head-to-head study results of weight-loss version tirzepatide Zepbound and weight-loss version semaglutide Wegovy. Eli Lilly released a press release on its official website stating that in the SURMOUNT-5 phase 3b open-label randomized clinical trial, participants using Zepbound lost an average of 50.3 pounds (22.8 kg), while those using Wegovy lost an average of 33.1 pounds (15.0 kg); analysis showed that Zepbound's relative weight loss effect was 47% higher than that of Wegovy. On average, Zepbound achieved a 20.2% weight reduction, while Wegovy achieved 13.7%.

Tirzepatide seems to have outperformed semaglutide. However, from a sales perspective, both Tirzepatide and semaglutide are still experiencing rapid growth.

Novo-Nordisk A/S's Q3 2024 report shows revenue of 204.7 billion Danish Kroner for the first three quarters, equivalent to 29.46 billion USD, a year-on-year increase of 23%. Net income is 72.758 billion Danish Kroner, equivalent to 10.47 billion USD, a year-on-year increase of 18%.

Among them, the sales revenue of the injectable glucagon-like peptide-1 (GLP-1) Ozempic reached 86.489 billion Danish Kroner, equivalent to 12.437 billion USD, a year-on-year increase of 32%; the oral GLP-1 version Rybelsus had sales of 16.384 billion Danish Kroner, equivalent to 2.356 billion USD, a year-on-year increase of 29%; the weight-loss version Wegovy recorded sales of 38.34 billion USD, equivalent to 5.513 billion USD, a year-on-year increase of 77%. The total sales of semaglutide amounted to 20.306 billion USD, accounting for 69% of Novo-Nordisk's revenue.

Eli Lilly and Co's Q3 2024 Earnings Reports indicate that the company's total revenue reached 31.51 billion USD, a year-on-year increase of 27.21%, with a net income of 6.18 billion USD, a year-on-year increase of 102.58%. Tirzepatide has played a significant role, with total sales reaching 11.028 billion USD in the first three quarters, including 8.01 billion USD for the glucose-lowering version Mounjaro, and 3.018 billion USD for the weight-loss version Zepbound, which just received FDA approval in November 2023.

Industry insiders have told Blue Whale Finance that in terms of GLP-1 drug development, there seems to be aesthetic fatigue regarding the simplistic perspective of "rapid weight loss", while the focus is shifting towards healthy and long-term weight loss, with fewer side effects and more convenient administration as future research breakthroughs.

On October 17 this year, the National Health Commission released the 'Guidelines for the Diagnosis and Treatment of Obesity (2024 Edition)', pointing out that a real-world study based on the American population found that among patients who started using GLP-1 as a weight loss drug in 2021, about 2/3 discontinued GLP-1 within a year for various reasons (including drug side effects, economic burdens, insurance coverage, etc.). Some studies have already focused on the weight loss effects after stopping GLP-1, with results showing varying degrees of weight rebound after discontinuation, while continued use of the drug can further reduce weight.

A study published last year in the Journal of the American Medical Association indicated that after using Eli Lilly and Co's weight loss drug Zepbound for about eight months and then stopping, participants experienced a gradual weight rebound, regaining half of the weight lost within a year.

As the market demand for weight loss drugs like Wegovy and Zepbound surges, concerns about the potential risk of muscle loss associated with these types of drugs have also increased.

With the competition in weight loss thriving, where is it headed in the future?

Dr. Qian Lei, Vice President of Clinical Development at INNOVENT BIO, stated to Blue Whale Finance that in fact, in response to unmet clinical needs, the competition in weight loss is showcasing a diversified landscape. We have already seen extensive efforts from both academia and industry, such as facilitating drug administration, including oral administration and injections; previously daily injections are now being developed into weekly injections, with the possibility of achieving monthly injections in the future. Moreover, efforts aim to reduce side effects like vomiting and diarrhea, minimize muscle loss, and prevent weight rebound. These are current breakthrough directions in research and development.

Institutions predict that by 2030, the global market for GLP-1 receptor agonist drugs will grow to 40.7 billion USD, being regarded as the next generation drug king after Semaglutide and K drug. The competition in the R&D of weight loss drugs seems to be heading towards 'targeted breakthroughs'. Internationally, apart from Novo-Nordisk A/S and Eli Lilly and Co, companies like Boehringer Ingelheim, Amgen, and Roche are also laying out plans in this field, while domestically, the competition in GLP-1 class weight-loss drugs is entering a heated stage.

In June of this year, the National Medical Products Administration (NMPA) approved the market application of Novo-Nordisk A/S's semaglutide (used for long-term weight management) in China. Eli Lilly and Co’s tirzepatide 'weight loss injection version' was also approved by the National Medical Products Administration in July this year.

It is noteworthy that the core compound patent of semaglutide, 'acylated GLP-1 compound', will expire on March 20, 2026. In April 2023, UNITED LAB's wholly-owned subsidiary, UNITED BIOTECH (Zhuhai Hengqin), submitted a clinical trial application for semaglutide weight management indications and became the first company in the country to obtain clinical approval for this biosimilar drug's weight management indications. Additionally, companies such as Jiuyuan Gene, Livzon Pharmaceutical Group Inc., CSPC PHARMA, Chengdu Better, Hybio Pharmaceutical, SIHUAN PHARM's Huisheng Biotech, Huadong Medicine, Imeik Technology Development, and China Resources Double-Crane Pharmaceutical have also been granted approval for clinical trials of semaglutide biosimilar's weight management indications.

Furthermore, INNOVENT BIO's Masydu-like peptide injection, which is the world's first GLP-1R/GCGR dual-target agonist to enter Phase III clinical trials, has garnered considerable attention in the industry. It is reported that its applications for weight loss and type II diabetes indications has been submitted and accepted, with rapid progress.

In May of last year, INNOVENT BIO announced that the results of the high-dose Phase II clinical trial showed that the 9 mg dose of Masydu-like peptide achieved significant weight loss effects after 24 weeks of treatment, reaching a weight reduction of 15%, demonstrating good weight loss outcomes. Moreover, personalized drug administration schemes have been developed for Masydu-like peptide for different degrees of obesity, with drugs available in dual specifications of 6 mg and 9 mg for different indications. It is also noteworthy that Masydu-like peptide has unique liver benefits.

Among the 69 subjects with a baseline liver fat content (LFC) of 5% or more enrolled in the early stage, after completing 48 weeks of the study, a significant correlation was observed between liver fat content and medication. Among subjects with baseline LFC ≥ 5%, after 48 weeks of treatment, liver fat content in the 4 mg Masydu-like peptide group and the 6 mg Masydu-like peptide group decreased by 63.3% and 73.2%, respectively. In subjects with more severe fatty liver (LFC ≥ 10%), the liver fat reduction ratio in the 6 mg Masydu-like peptide group reached 80.2%.

Innovent Bio stated that the weight loss indication is expected to be approved in the first half of next year, while the diabetes indication is expected to be approved in the second half of next year.

In addition to Innovent Bio, Jiangsu Hengrui Pharmaceuticals is also making significant investments in this field. Its investigational small molecule GLP-1 receptor agonist HRS-7535, an oral medication, is currently in Phase II clinical trials; another GLP-1R/GIPR dual agonist HRS9531 is available in both injectable and oral forms, with the HRS9531 injection having entered Phase III clinical trials. Furthermore, Huadong Medicine, CSPC PHARMA, HANSOH PHARMA, and others are also developing new drugs.

However, with the continuous increase in market demand, whether production capacity can keep up with the rapid growth of demand is another concern of the market. This year, Novo-Nordisk and Eli Lilly and Co are both actively expanding their production capacity. On February 5, Novo-Nordisk announced an investment of $11 billion to acquire three filling and packaging bases from the pharmaceutical giant Catalent; on March 19, Novo-Nordisk announced an additional investment of approximately $0.556 billion (about 4 billion yuan) in Tianjin to expand sterile formulation production capacity, with expectations that the expansion will be completed by 2027; on June 25, on the day of its approval, Novo-Nordisk announced a new investment plan to build a second filling and finishing manufacturing facility in Clayton, North Carolina, USA, covering an area of 1.4 million square feet to enhance the production capacity for semaglutide-related drugs Wegovy and Ozempic, with a total investment of $4.1 billion.

Regarding Eli Lilly and Co, on October 11, it announced a large-scale global capacity upgrade plan, deciding to invest 1.5 billion yuan to upgrade the production capacity of its Suzhou factory to meet the needs of Chinese patients and support pipeline product production.

However, there are market rumors that due to difficulties in simultaneously meeting domestic and overseas market demands, and because Chinese drug prices may be lower than those in foreign markets, these two companies may implement purchasing restrictions in China, which may also provide domestic companies with an opportunity to position themselves.