Novo Nordisk’s triple agonist UBT251 delivered a mean weight loss of 19.7% after 24 weeks in a Phase 2 trial in China, the company announced on Tuesday. UBT251 is a triple agonist of the receptors for GLP-1, GIP and glucagon (triple G) and is being jointly developed with United Biotechnology. 

Bagsværd, Denmark. Credit: Novo Nordisk

The trial was conducted by United Biotechnology, which is responsible for the development of the drug in China, Hong Kong, Macau and Taiwan. From a baseline mean body weight of 92.2 kg, the highest mean weight loss observed was 19.7%, about 17.5 kg, compared to 2.0%, about 1.6 kg, for placebo after 24 weeks of treatment. 

The triple agonist advantage

The first GLP-1 receptor agonist was approved in 2005, followed by the first glucagon and GLP-1 receptor co-agonist in 2022. After this, GIP/GLP-1 dual agonists emerged, including tirzepatide. The success of dual agonists paved the way for triple GIP/GLP-1/glucagon agonists. 

The triple agonist acts on three receptors: GLP-1, GIP and glucagon. GLP-1 reduces appetite and slows gastric emptying. GIP enhances the effects of GLP-1 and increases lipolysis. Glucagon stimulates energy expenditure, increasing fat oxidation and thermogenesis. It also triggers lipid catabolism and reduces food intake. The addition of the glucagon agonist allows triple agonists like UBT251 to deliver more weight loss than dual agonists like tirzepatide. 

While glucagon does raise blood sugar, the dual incretin activity of GLP-1 and GIP offset these hyperglycemic effects while retaining the energy expenditure benefits. 

Eli Lilly’s retatrutide is the most advanced triple agonist globally, with Phase 3 data showing up to 28.7% weight loss at 68 weeks. UBT251 showed 19.7% weight loss at 24 weeks. Comparisons are difficult at this stage, with the studies having different populations and durations, but UBT251’s data is certainly notable. 

UBT251’s Phase 2 trial 

The trial was a randomized, double-blind, placebo-controlled trial with 205 patients who were overweight or obese with at least one weight-related comorbidity. 

All dose groups—2 mg, 4 mg and 6 mg—showed statistically significant improvements relative to placebo on secondary endpoints including waist circumference, blood glucose, blood pressure and lipids. The drug appeared to have a safe and well-tolerated profile, with some gastrointestinal adverse effects, consistent with incretin-based therapies. 

 “The success of the Phase 2 clinical trial of UBT251 in China represents another significant milestone in TUL’s innovation-driven development,” Tsoi Hoi Shan, chairman of TUL, which owns United Biotechnology, said in a statement. 

Novo Nordisk plans to report data from a global trial of UBT251 next year, Martin Holst Lange, executive vice president, chief scientific officer and head of Research and Development at Novo Nordisk, said in the statement. The global trial is a Phase 1b/2a trial investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of the doses of UBT251 for up to 28 weeks in about 330 people who are overweight or obese. Novo Nordisk also said it expects to initiate a Phase 2 trial of UBT251 in people with Type 2 diabetes in the second half of 2026. 

More results from the Chinese Phase 2 trial will be presented at a medical congress later this year. United Biotechnology is planning to initiate a Phase 3 trial in Chinese patients who are overweight or obese. 

The CagriSema trial failure

This news comes just after Novo Nordisk announced that another weight-loss treatment, CagriSema, did not reach primary endpoints in its Phase 3 trial, failing to demonstrate non-inferiority to tirzepatide. CagriSema, a combination of cagrilintide and semaglutide, achieved 23% weight loss after 84 weeks of treatment, compared to 25.5% with tirzepatide. The treatment was safe and well tolerated, with mostly mild to moderate gastrointestinal adverse effects reported, consistent with other GLP-1s, the company said. 

Novo Nordisk stock was down 15% Monday afternoon following the announcement. The stock continued to fall slightly on Tuesday following the UBT251 announcement, hovering at $38.54 Tuesday afternoon after closing at $39.88 on Monday. 

Filed Under: Endocrinology, Gastroenterology, Metabolic disease/endicrinology
Tagged With: CagriSema, China, do the same for this article:1:14 PMUBT251, Eli Lilly, GIP, GLP-1, glucagon, incretin, lipolysis, Novo Nordisk, obesity, Phase 2, Phase 3, retatrutide, stock, thermogenesis, Tirzepatide, triple agonist, United Biotechnology, weight loss