According to clinical registration information, NA-931 is a multi-target agonist that covers four targets: GLP-1, GIP, GCG, and IGF-1. According to preclinical research data released by Biomed Industries at the meeting of the American diabetes Association (ADA), NA-931 was defined as a three target agonist at that time, including GLP-1, GIP and IGF-1. Animal experiment results show that the weight loss effect of NA-931 is comparable to that of tilboptin, and can significantly reduce plasma triglyceride levels by 34% and liver triglyceride levels by 46%.
With the continuous expansion of the weight loss market, companies such as Eli Lilly and Novo Nordisk have also benefited from it, with significant performance growth. More and more pharmaceutical companies are entering this field, promoting the development of GLP-1 and its subsequent multi-target small molecule drugs, while actively exploring new mechanisms, striving to achieve ideal therapeutic effects of weight loss without muscle loss.
The rapid growth of the global overweight and diabetes population has given birth to the 100 billion market of GLP-1 drugs, and has also pushed its upstream API industry into a golden age. A value reconstruction towards multi-target, oral, and long-acting approaches has begun. In recent years, with the continuous deepening of research on obesity and related metabolic diseases, new intestinal insulinotropic drugs including glucagon like peptide-1 (GLP-1) agonists, dual glucose dependent insulinotropic peptides (GIP), and GLP-1 receptor agonists have gradually become a research hotspot in the medical field.
In 2025, semaglutide (GLP-1 receptor agonist) and tilboptide (GLP-1 and GIP dual receptor agonist) continued to achieve impressive sales performance. Multi targeted GLP-1 receptor agonists continue to appear.
1. GLP-1 dual receptor agonist
Tilpoltide is the first approved GLP-1/GIP dual receptor agonist in the world. It was approved by FDA for type 2 diabetes (trade name: Mounjaro) in 2022, and for obesity (trade name: Zepbound) in 2023.
In June 2025, the Masidomide (Xinermei) developed by Xinda Biotechnology was officially approved for marketing. As the world's first approved GCG (Glucagon)/GLP-1 dual target agonist weight loss drug, its approval marks an important breakthrough in China's related treatment field.
CT-388 is a synthetic polypeptide developed by Carmot Therapeutics. It is a weekly subcutaneous injection of GIP/GLP-1 receptor agonist. It is being developed for the treatment of obesity and type 2 diabetes, and is currently in phase II clinical stage.
Zenagamtide (Amycritin; NN 9487) is a glucagon like peptide (GLP-1) and amylin receptor agonist. On November 25, 2025, Novo Nordisk announced that its research drug Amycretin had achieved positive top line results in the phase II clinical trial for patients with type 2 diabetes. This is the first time that Amycretin has carried out an evaluation among people with type 2 diabetes, which not only highlights the dual potential of the drug in the field of glucose reduction and weight loss, but also further consolidates Novo Nordisk's leading position in the field of treatment innovation of type 2 diabetes.
The weekly injection of erythromycin treatment helped overweight patients lose 22% of their weight within 36 weeks; Amycretin oral formulations helped patients lose up to 13.1% of their weight within 12 weeks. These positive results have laid a solid foundation for the further development and application of amycycline, and have also brought new treatment hopes for obese patients.
2. GLP-1 triple receptor agonist
Retalutide is an active compound released by Eli Lilly in June 2023. It is a developed drug for the treatment of obesity and type 2 diabetes, based on the GLP/GIP dual receptor agonist Tirzepatide, which can achieve triple (GLP-1/GIP/GCG) agonist effect by hybridizing glucagon related structures. This active compound can activate receptor agonists in the body, helping to control blood sugar and weight loss management. The 12 week phase 1b clinical trial for patients with type 2 diabetes from December 18, 2018 to December 28, 2020 showed that the three high-dose groups of Retatrutide were significantly better than the placebo control group in reducing blood sugar and glycosylated hemoglobin (HbA1c), and showed a dose related weight loss effect. On August 12, 2023, the results of the second phase clinical trial of Retrutide for patients with type 2 diabetes were published in Lancet. The 12mg dose group of retatrutide was significantly better than 1.5mg dulaglutide in reducing blood sugar HbA1c, while the 4mg and above dose groups were significantly better than 1.5mg dulaglutide in reducing body weight.
UBT251 is a three target receptor agonist independently developed by FedEx, targeting GLP-1, GIP, and GCGR hormone receptors. In June 2025, Novo Nordisk, Pay a prepayment of $180 million (approximately RMB 1.293 billion) to Zhuhai United Laboratories in China to obtain global rights for its independently developed three target weight loss drug UBT251 outside of Greater China.
3. GLP-1 quadruplex receptor agonist
NA-931 is the world's first agonist targeting four receptors: IGF-1 (insulin-like growth factor-1), GLP-1 (glucagon like peptide-1), GIP (glucose dependent insulinotropic polypeptide), and GCG (glucagon). IGF-1 plays a key role in energy metabolism and body composition regulation, achieving weight loss without muscle loss. IGF-1 combined with GLP-1 and GIP has been proved to be effective in weight loss of non diabetes obese patients under the adjuvant treatment of diet and exercise.
NA-931 is a novel four target agonist that can simultaneously activate GLP-1, GIP, GCG, and IGF-1 receptors. The design of this agonist is based on a deep understanding of the structure and signaling pathways of these receptors, allowing a molecule to bind to its specific receptor and simulate the action of natural ligands, thereby activating downstream signaling pathways of the receptor. The pharmacokinetic data supports the once daily oral administration regimen of NA-931. Whether on an empty stomach or after a high-fat meal, the blood drug concentration of NA-931 remains consistent, indicating that the administration time of NA-931 is not limited by meal time, providing patients with greater flexibility.
4. GLP-1 pentareceptor agonist
From September 15 to 19, 2025, the 61st annual meeting of the European Association for diabetes Research (EASD) was held in Vienna. Dr. Daniela Liskiewicz of the Helmholtz Center in Munich (Germany diabetes Research Center) and her colleagues shared the research and development progress of a new "five fold agonist". This pentaagonist binds to GLP-1 and GIP dual receptor agonists, and binds to the lamifibror molecule, which can activate three different peroxisome proliferator activated receptors (PPARs) - PPAR - α, PPAR - δ, and PPAR - γ, all of which play important roles in energy regulation. Therefore, this new compound contains a total of five agonists. This innovative therapy not only activates GLP-1 and GIP receptors, but also contains a molecule that can activate three different peroxisome proliferator activated receptors.
Dr. Liskiewicz provided a detailed report on the design concept and preclinical evaluation results of this novel single-molecule pentaagonist. This innovative therapy cleverly combines the "weight reduction and blood glucose lowering" effects of GLP-1R and GIPR co activation with the "enhanced insulin sensitivity and regulation of dyslipidemia" characteristics of PPAR activation. The pan PPAR agonist in the five fold agonist can accurately target delivery to cells expressing GIP or GLP-1 receptors, thereby achieving precise action, and the principle behind this is relatively complex. PPARs belong to nuclear receptors, while GLP-1R and GIPR are cell membrane receptors. Due to the use of single-molecule drugs instead of combination therapy, lanifibror is not widely distributed throughout the body, but only in cells expressing GLP-1 and GIP cell surface receptors. After binding to GLP-1R/GIP receptors, the complex enters the cell, and PPAR agonists are released inside the cell, then enter the nucleus and exert their effects.
Preliminary animal experiments have shown that this new five fold agonist exhibits powerful effects. In diet induced obese mouse models and genetic obesity and diabetes models, the five agonists showed better weight loss effect, reduced food intake and improved hyperglycemia than GLP-1: GIP or smeglutide. These enhanced effects are attributed to the synergistic effect of the intestinal insulinotropic and PPAR pathways in the brain and adipose tissue. Dr. Liskiewicz concluded that GLP-1, GIP, and full PPAR agonists are significantly superior to using GLP-1, GIP, or full PPAR agonists alone or in a loose combination for weight loss and improved blood glucose control. This new five fold agonist provides unprecedented therapeutic potential for the treatment of obesity and type 2 diabetes.