[Edaily Reporter KIM SUNG-JIN ] “Disappointing Interim Results for GLP-1 Drug Therapy.”

This was the headline on a promotional brochure distributed by Donga ST(170900)at the Severe Diabetes Symposium held on the 15th at the COEX Magok Convention Center in Seoul. Donga ST set up a promotional booth to share information on diabetes trends and included this message. The company emphasized side effects, the risk of treatment discontinuation, and the uncertainty regarding cardiovascular benefits rather than weight loss effects.

Industry observers interpret this as an attempt by Donga ST—which has not yet commercialized its own obesity treatment—to convey a differentiated message in order to maintain the market position of its existing diabetes treatments. However, since Donga ST is also developing a new GLP-1-based obesity drug, the company finds itself in a situation where it must strike a balance between maintaining the competitiveness of its existing treatments and its new drug development strategy.

Highlighting Side Effects and Risk of Treatment Discontinuation Over GLP-1 Weight Loss Effects

The material in which Donga ST pointed out the limitations of GLP-1 referenced a comparative study on obesity treatments published last July in the British Medical Journal (BMJ), an international academic journal. The research team synthesized data from 99,791 participants across 262 randomized clinical trials to compare the weight loss effects, safety, and cardiovascular disease prevention efficacy of 19 obesity treatments.

The results showed that tirzepatide (a GIP/GLP-1 dual agonist) achieved an average weight loss of 14.9% over one year, while Cagrisema—a combination of cagrlinatide and semaglutide—achieved 14.8%. These are the highest levels among the drugs included in the study. Tirzepatide is the active ingredient in Mounjaro and Zepbound, developed by global pharmaceutical giant Eli Lilly, while Cagrisema is a new obesity treatment currently under development by Novo Nordisk; it has completed Phase 3 clinical trials and is currently undergoing regulatory review. Following these, weight loss effects were observed in the following order: oral semaglutide (10.9%), orogliflon (9.9%), subcutaneous semaglutide (9.8%), and phentermine-topiramate (8.1%).

The problem is that these weight-loss effects were accompanied by significant side effects. Tirzepatide, which showed the greatest weight-loss effect, was also found to cause the greatest reduction in lean body mass (-8.3%). Lean body mass refers to the weight of the body excluding body fat, such as muscle mass and water. Recently, concerns have been raised that GLP-1 receptor agonist weight-loss drugs cause a loss of muscle mass along with fat; consequently, preserving lean body mass has emerged as a new trend in the weight-loss drug market.

In particular, the greater the weight loss, the higher the rates of side effects and treatment discontinuation were consistently found to be. Among the 19 obesity treatments, the subcutaneous injection semaglutide was the only drug shown to definitively reduce the risk of heart failure.

In its brochure, Donga ST stated, “Weight regain was expected after discontinuing obesity treatment, and patients had fully returned to their pre-treatment weight after 1.7 years.” The company added, “The results show that drugs with greater weight-loss effects are associated with higher levels of side effects—such as gastrointestinal disorders and fatigue—and a higher risk of treatment discontinuation, while having no impact on improving quality of life.”

In-house Obesity Drug Still in Phase 1… Challenge of Maintaining Market Position for Existing Diabetes Drugs

Another point worth noting is the other studies introduced in the same Donga ST brochure. The study presented by Donga ST indicated that low-dose SGLT2 inhibitors were effective for heart failure in patients with diabetes. The group receiving a low dose of 5 mg of the SGLT2 inhibitor outperformed the group receiving the standard dose of 10 mg in terms of cardiovascular mortality, hospitalizations for heart failure, and emergency room visits.

Donga ST stated, “While 10 mg of dapagliflozin is used more frequently than 5 mg in the United States, it is reported that 5 mg is prescribed more often than 10 mg in Japan, where the population is older and of smaller stature,” adding, “Low-dose SGLT2 inhibitors are likely to be useful in Korea as well.” The brochure is structured to highlight the limitations of GLP-1 agonists while also emphasizing the clinical value of existing diabetes treatments.

In particular, Donga ST markets “Dafapro,” an SGLT2 inhibitor containing the active ingredient dapagliflozin mentioned in this brochure. Dapapro is a diabetes treatment launched by Donga ST in December 2022 and is considered one of the company’s flagship diabetes treatments, alongside Suganon, a domestically developed DPP-4 inhibitor.

Donga ST’s decision to structure its promotional materials in this way is attributed to its current business structure and recent expansion into the obesity treatment sector. This is because GLP-1 agonists, such as Wegovy and Mounjaro, are broadening their scope beyond obesity to include diabetes and cardiovascular diseases, thereby altering the competitive landscape with existing diabetes treatments.

Of course, this does not mean that Donga ST is passive in the development of obesity treatments. On the contrary, the company is accelerating the development of its own obesity treatments. A prime example is “DA-1726,” currently under development through its U.S. affiliate, Metavia. DA-1726 is a dual-acting agent that targets both the GLP-1 and glucagon receptors; it combines the appetite-suppressing effects of GLP-1 with glucagon’s ability to promote energy expenditure.

According to Phase 1 clinical trial results released by Metavia, an average weight loss of 9.1% was observed in the 48 mg dose group after 54 days. The company is currently conducting Part 3 of the Phase 1 trial, which involves a stepwise dose escalation of 48 mg and 64 mg. In May, it also began a Phase 1 clinical trial for another obesity treatment candidate, “DA-5227.”

The issue is that the obesity treatments currently under development by Donga ST are still in the early stages. In addition to Wegovy and Mounjaro, HanmiPharm has already received approval from the Ministry of Food and Drug Safety for “Epe” (active ingredient: efeglenatide)—the first obesity treatment in Korea—and is poised to enter the market. Since it will take a considerable amount of time for Donga ST to commercialize its own obesity treatments, maintaining the prescription base for its existing diabetes treatments and securing market competitiveness in the meantime has emerged as a critical challenge.

Regarding this, an industry official explained, “As the popularity of obesity treatments increases and their scope of use expands, the market position of existing diabetes treatments could be squeezed.”

A Donga ST spokesperson explained, “This material was produced to provide medical information to healthcare professionals based on the latest trends in diabetes treatment and related academic papers.”