The obesity treatment market is rapidly evolving beyond simple weight loss, shifting toward competition centered on innovations in dosage forms, administration schedules, and mechanisms of action. As the market evolves from a focus on injectables to oral medications, long-acting formulations, and multi-action drugs, the treatment paradigm is also changing. Global pharmaceutical companies and domestic biotech firms are accelerating the development of next-generation obesity drugs. Accordingly, Edaily is shining a spotlight on the changes in obesity and diabetes treatment and the response strategies of K-Bio as we enter the “post-GLP-1” era. This report was produced with the support of the Korea Science Journalists Association. [Editor’s Note]

[Edaily Reporter YU JIN-HEE ] The obesity treatment market is rapidly restructuring beyond simple weight loss, shifting toward competition in innovations related to dosage forms, administration schedules, and mechanisms of action. As the market evolves from an injection-centered approach to oral medications, long-acting formulations, and multi-action agents, the treatment paradigm is also changing. Global pharmaceutical companies and domestic biotech firms are accelerating the development of next-generation obesity drugs. Accordingly, Edaily is shining a spotlight on the changes in obesity and diabetes treatment in the “post-GLP-1” era and the response strategies of K-Bio. This report was produced with the support of the Korea Science Journalists Association. [Editor’s Note]

A “second war” has begun in earnest in the global pharmaceutical and biotech market surrounding glucagon-like peptide-1 (GLP-1) receptor agonists. This comes as global big pharma companies, leveraging their massive financial resources, are expanding beyond the early obesity and diabetes markets—which had been dominated by Novo Nordisk’s “Wegovy” (active ingredient: semaglutide) and Eli Lilly’s “Zepbound” (active ingredient: tirzepatide)—and are now achieving results one after another in indications for systemic metabolic and inflammatory diseases.

As big pharma companies use their global clinical trial infrastructure—which requires investments of hundreds of billions of won just for Phase 3 trials—to build high barriers to market entry, industry attention is focused on the realistic survival strategies that domestic pharmaceutical and biotech companies must adopt. Market experts agree that, given the clear limitations of their capital, domestic companies must avoid head-on competition and instead identify combination targets that overcome the critical side effects of existing GLP-1 agents, develop formulation-modification platforms, or secure niche indications that big pharma has not yet targeted—only then can they achieve technology transfer (L/O) deals worth trillions of won and commercial success.

Big Pharma’s Territorial Expansion… Building Barriers to Entry by Sweeping Up Phase 3 Trials for MASH, CKD, and Heart Failure

The focus of the global obesity treatment market has already shifted from “who can help patients lose the most weight” to “how to lose and maintain weight in a healthy way.” This is because addressing the three major limitations of existing GLP-1 agonists—△muscle loss (decrease in lean body mass), △gastrointestinal (GI) adverse reactions such as nausea and vomiting, and △the yo-yo effect after discontinuation—is considered the core competitive advantage of next-generation obesity treatments.

In fact, the fact that 20–40% of total weight loss when taking Wegovy or Zepbound results from the loss of lean body mass—such as muscle—is cited as a cause of “sarcopenic obesity,” which can be fatal for elderly patients. Consequently, major global pharmaceutical companies have rushed to initiate Phase 3 trials combining myostatin (a protein that inhibits muscle growth) blocking antibodies or selective androgen receptor modulators (SARMs). Regeneron has secured data showing that in a clinical trial combining semaglutide with the myostatin inhibitor “treboglumab,” and is now advancing through late-stage clinical trials. Similarly, the U.S.-based company Veru is validating the efficacy of its drug “enobosam” in selectively burning body fat and preserving skeletal muscle through a Phase 2b/3 trial.

Competition is also fierce to alleviate gastrointestinal side effects and improve medication adherence. Novo Nordisk is aiming to improve tolerability and overcome weight plateaus through the “REDEFINE” Phase 3 trial of “Cagrisema,” which combines a GLP-1 receptor agonist with an amylin analog, a satiety-inducing hormone. Lilly is simultaneously demonstrating the efficacy of its once-daily oral small-molecule compound “Orfoglifron” through the large-scale “ATTAIN” Phase 3 trial to address aversion to injections and suppress weight regain (yo-yo effect) after discontinuation.

The company is also aggressively expanding its pipeline by linking the weight-loss mechanism of GLP-1 to systemic organ protection. This is a strategic move to position its products not merely as treatments for simple obesity, but as standard first-line therapies for chronic diseases.

The fiercest battleground is metabolic and alcoholic steatohepatitis (MASH). Novo Nordisk is targeting the resolution of MASH without fibrosis progression and the improvement of fibrosis through its ongoing global Phase 3 “ESSENCE” program, which involves approximately 1,200 patients with stage 2–3 liver fibrosis (F2–F3). Eli Lilly, too, building on the success of tirzepatide’s Phase 2 trials, has launched a large-scale confirmatory Phase 3 trial to verify the drug’s ability to inhibit the long-term progression of liver cirrhosis and prevent major clinical events.

Phase 3 data is also pouring in from the chronic kidney disease (CKD) and cardiovascular fields. Novo Nordisk early terminated its “FLOW” Phase 3 trial—which enrolled approximately 3,500 patients with CKD and type 2 diabetes—after demonstrating a 24% reduction in the risk of kidney function decline and cardiovascular death compared to placebo, and has since initiated the approval process for the indication. Lilly has also launched the “TREASURE-CKD” Phase 3 trial targeting a broad population of patients with kidney disease.

In addition, Eli Lilly opened new horizons for the first-ever pharmacological treatment through its Phase 3 “SURMOUNT-OSA” trial, which reduced the apnea-hypopnea index (AHI) by up to approximately 60% in patients with moderate-to-severe obstructive sleep apnea (OSA). Novo Nordisk is accelerating the expansion of its indications by successively completing large-scale Phase 3 clinical trials, such as “STEP-HFpEF” for heart failure with preserved ejection fraction (HFpEF) and “STEP 9” for the relief of knee osteoarthritis pain.

Given this situation, analysts believe it will be difficult to survive in the GLP-1 market without carving out a niche among the big pharma players. The suspension of development of the “ D&D Pharmatech Inc.(347850) ” pipeline—which had been leading the field—is a prime example. Previously, D&D Pharmatech Inc. signed a technology transfer agreement worth approximately $800 million (about 1 trillion won) with U.S.-based Metcera for a total of six pipeline candidates—including oral obesity candidates (DD02S, DD03, etc.)—leveraging its proprietary peptide oral delivery technology, the “ORALINK” platform, and multi-agent technology. However, Pfizer, the global pharmaceutical and biotech company that has become Metcera’s new owner, halted development of “MET-224o” last May. MET-224o is a compound that utilizes D&D Pharmatech Inc.’s ORALINK technology. Industry observers believe that, given Pfizer’s position as a relative latecomer in the obesity treatment market, the company is focusing on developing products that can differentiate themselves from its existing approved products.

Korean Biotech Companies Target ‘Unexplored Niche Indications’ with Long-Acting Platforms, BBB Penetration, and Intestinal Mucosal Regeneration

In the highly competitive global GLP-1 market, innovation in convenience is still cited as the surest way for domestic companies to survive. This is because it directly aligns with the interests of global Big Pharma, which must prepare for the patent expiry of original blockbuster drugs and improve patient adherence.

In the field of sustained-release injectables, which dramatically extend dosing intervals, Inventage Lab Inc.(389470)is achieving concrete results in advancing to global clinical trials. Inventage Lab Inc. has commenced a Phase 1 clinical trial in Australia for “IVL3021,” an obesity treatment that transforms the existing once-weekly semaglutide into a “once-monthly” formulation by applying its microfluidics-based long-acting injectable platform, “IVL-DrugFluidic.”

The company has secured preclinical data demonstrating that the formulation prevents initial excessive drug release and maintains consistent blood concentrations over a month, and plans to validate human pharmacokinetic (PK) data in the Australian Phase 1 trial to fully launch its global technology transfer efforts. Following its joint development with Yuhan(000100), Inventage Lab Inc. is accelerating the development of “IVL3024,” a tirzepatide-based, once-monthly long-acting follow-up pipeline, targeting global life cycle management (LCM) demand.

Among the pipelines designed to fundamentally prevent muscle loss—the greatest drawback of weight loss— HanmiPharm(128940)is currently on the most aggressive clinical track. HanmiPharm has obtained U.S. Food and Drug Administration (FDA) clinical approval for “HM15275,” a triple-action GLP-1/GIP/glucagon agonist targeting high-intensity weight loss of up to 25% or more, and is accelerating its development.

At the same time, the company has received an Investigational New Drug (IND) approval from the FDA for a Phase 1 clinical trial of “HM17321” (a Urocortin-2 analog), a “next-generation muscle-preserving obesity drug” that stimulates muscle growth and burns fat, and is currently administering the drug to patients. Through these efforts, HanmiPharm is building a global clinical data set for “next-generation qualitative weight loss combination therapy” that goes beyond simple weight loss to preserve lean body mass, thereby maximizing its bargaining power in partnership negotiations with Big Pharma.

In addition to platform technologies, a key strategy for domestic biotech companies is to secure a head start in “unexplored indications” where global pharmaceutical and biotech firms have not yet made a significant inroads. Representative examples include treatments for central nervous system (CNS) disorders that incorporate blood-brain barrier (BBB) penetration technology and differentiated targets for organ metabolism regulation.

D&D Pharmatech Inc.(347850)The company has accumulated experience by developing “NLY01,” a brain-penetrating GLP-1 candidate designed to block chronic neuroinflammation in microglia within the brain, and has completed a global Phase 2 trial in patients with Parkinson’s disease and Alzheimer’s disease. This asset addresses the limitations of existing obesity treatments, which have struggled to directly treat neurological diseases due to low BBB permeability. The company is currently pursuing the expansion of indications to rare inflammatory neurological diseases, such as multiple sclerosis (MS), and is targeting independent technology transfers.

Peptron, Inc.(087010) Similarly, led by “PT320”—which integrates the company’s proprietary sustained-release platform, “SmartDepot,” with exenatide, a compound that exhibits relatively high BBB permeability—the company has completed a Phase 2 clinical trial in Korea for the treatment of Parkinson’s disease and is currently analyzing the data. Its key advantage is a controlled-release profile that minimizes the weight loss side effects typical of obesity drugs, allowing the treatment to focus solely on inhibiting neuronal cell death in the brain.

ProGen is breaking new ground in personalized patient treatment through a unique combination of hormones. Based on its proprietary fusion protein platform “NTIG,” ProGen is developing “PG-102,” a dual agonist that simultaneously activates the GLP-1 and GLP-2 receptors, which promote intestinal function and mucosal regeneration.

In a domestic Phase 2a clinical trial involving 48 patients with Type 2 diabetes, ProGen confirmed that ‘PG-102’ reduced glycated hemoglobin (HbA1c) by up to 1.44% while demonstrating the feasibility of biweekly and monthly dosing. Notably, clinical data showed that 87.5% of the weight loss came from body fat, indicating limited loss of lean body mass (muscle). Building on these clinical results, ProGen is pursuing a listing under the technology exemption program and is exploring the expansion of multinational clinical trials and global technology transfers for rare gastrointestinal diseases accompanied by intestinal mucosal damage and muscle-preserving metabolic disorders.

HanmiPharm has repurposed “Epegeglucagon” (HM15136), a long-acting glucagon analog derived from its incretin research, as a treatment for “congenital hyperinsulinism,” a rare pediatric disorder characterized by brain damage caused by excessive insulin secretion. After consecutively securing Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) from the FDA, the company has completed the key dosing phase of its global Phase 2 trial and is now on the fast-track to approval.

Hong Soon-jae, CEO of Biobook, stated, “It is practically impossible for a domestic company with limited capital to venture alone into a global Phase 3 trial—which costs trillions of won—and go head-to-head with Big Pharma,” adding “Ultimately, the most reliable and proven survival strategy for K-Bio is to seize gaps in the massive markets established by global leaders—such as combination therapies that prevent muscle loss, formulation innovations like once-monthly injections or oral medications, and rare niche indications overlooked by Big Pharma—to secure early technology transfers (L/O),” he emphasized.

Meanwhile, according to research by the U.S. global investment bank Morgan Stanley, the global GLP-1 market is projected to exceed $105 billion (approximately 141 trillion won) by 2030 and grow to as much as $150 billion (approximately 201 trillion won) by 2035, when the expansion of indications for chronic diseases such as MASH and heart failure, along with the widespread adoption of oral formulations, gains momentum.