Beyond GLP-1 to the Era of Combined Targets: "Next-Generation Obesity Drugs May Enable 20% Weight Loss"

by Park Jeongyeon

Published 12 Feb.2026 09:15(KST)

Professor Lim Soo's Team at Seoul National University Bundang Hospital Outlines Future Directions for Type 2 Diabetes and Obesity Therapies
Overview of New Drug Development Targeting Multiple Pathways Including GIP, Glucagon, and Amylin
"The Greater the Efficacy and Convenience, the More Carefully Adverse Effects Must Be Monitored"

There is an emerging view that obesity treatments, represented by glucagon-like peptide-1 (GLP-1) receptor agonists, are evolving from a single-mechanism approach into a "combined modulation" strategy that targets multiple metabolic hormones simultaneously. Development of next-generation drugs aiming for more than 20% weight loss is now in full swing, going beyond existing therapies that show an average weight reduction of around 15%. At the same time, formulations are expanding from injectables to oral agents.

From left: Im Su, Professor of Endocrinology at Seoul National University Bundang Hospital, and Son Jangwon, Professor at Bucheon St. Mary's Hospital. Seoul National University Bundang Hospital

Seoul National University Bundang Hospital announced on the 12th that the research team led by Professor Lim Soo of the Department of Endocrinology and Metabolism, together with the team of Professor Son Jangwon at Bucheon St. Mary's Hospital and Dr. Michael A. Nauck of Ruhr University Bochum in Germany, has published a review article summarizing the development trends of therapies for type 2 diabetes and obesity in the international journal Endocrine Reviews.

Currently, obesity treatment is dominated by GLP-1-based drugs. Representative examples include Wegovy, which contains semaglutide, and Mounjaro, which contains tirzepatide, a dual GIP/GLP-1 agonist. These drugs promote weight loss by modulating incretin hormones secreted in the intestine to suppress appetite and delay gastric emptying. Their average weight reduction rate has been reported to be around 15%.

The article analyzes that recent research trends are shifting from GLP-1 as a single target toward multi-agonists that simultaneously act on various metabolic pathways, including GIP, glucagon, amylin, and PYY. It explains that new drug candidates are being developed with the goal of achieving more than 20% weight loss through combined mechanisms that both reduce food intake and increase energy expenditure.

Changes are also underway in terms of formulation. Most existing GLP-1 drugs have been administered as subcutaneous injections, but in recent years, research on candidates that can be given orally has expanded by enhancing their stability in the acidic gastric environment and against digestive enzymes. This is evaluated as an attempt to improve patient adherence and accessibility.

The researchers pointed out that the importance of managing adverse effects increases as the magnitude of weight loss grows. In clinical trials of existing GLP-1 drugs, approximately 20% to 30% of total weight loss has been reported to be associated with a reduction in lean body mass. Accordingly, strategies to minimize the risk of sarcopenia during long-term treatment have been proposed as a key task in the development of next-generation drugs. Gastrointestinal side effects such as nausea, vomiting, and diarrhea are relatively common, but they explained that starting at a low dose and titrating up stepwise can improve tolerability.

Research and development are underway on approaches targeting various pathways, including GLP-1, GIP, and glucagon. Graphic showing trends in obesity drug research. Seoul National University Bundang Hospital

The benefits of GLP-1 drugs are not limited to weight loss. Large-scale study results have shown that semaglutide reduced the risk of major kidney events by 24% and overall mortality by 20% in patients with diabetes and chronic kidney disease. These findings are interpreted as evidence supporting an integrated treatment strategy that takes into account the interrelationship among diabetes, cardiovascular disease, and kidney disease.

Professor Lim said, "Recently, new obesity and diabetes treatments that combine various incretins on a GLP-1 backbone are being developed, attracting worldwide attention, and I expect that the advent of next-generation anti-obesity drugs that modulate energy intake, absorption, and expenditure in a combined and integrated manner is not far off," adding, "As new drugs emerge and weight-loss efficacy increases, it will be necessary to monitor adverse effects closely."