UBT251, the triple hormone-receptor agonist developed by United Biotechnology and licensed by Novo Nordisk for treatment of type 2 diabetes and obesity, has achieved good blood sugar-lowering and weight loss results in Phase II in a Chinese study.

As reported in Cell Metabolism, people with type 2 diabetes treated with the novel triple glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor agonist had average glycated hemoglobin (HbA1c) reductions of approximately two percentage points and average weight losses of approximately 8–10% compared with their levels at enrollment.

Eli Lilly also has a similar triple hormone-receptor agonist candidate drug in development called retatrutide, which achieved excellent results at Phase III last month, but is not yet FDA-approved. The main hoped-for addition in adding glucagon-receptor activation to the already approved dual agonist drugs is greater energy expenditure alongside GLP-1’s effect of making people eat less and reducing HbA1c.

UBT251 is a potential competitor for retatrutide but is somewhat behind in development timing. It was initially developed by Chinese biotech United Biotechnology, which still has rights to the drug in mainland China, Hong Kong, Macau, and Taiwan, but Novo entered a licensing deal with United last year and has the right to develop the drug everywhere else.

United has already started a Phase III program in China in both type 2 diabetes and obesity patients and Novo is completing a separate trial program outside China that is currently at the Phase Ib–II stage for both conditions.

The current study reports results from United’s Phase II study in patients with type 2 diabetes. Researchers randomized 211 Chinese adults with inadequately controlled type 2 diabetes to weekly injections of UBT251 at doses of 2, 4, or 6 mg, semaglutide 1 mg or placebo for 24 weeks. Only the semaglutide arm was unblinded.

At 24 weeks, the highest reduction in HbA1c was 2.16 percentage points in the 2 mg/week group, with all UBT251 treated individuals achieving a reduction of at least 1.98 points from the start of the study. In contrast the reduction in the semaglutide group was 1.77 points and 0.66 points in the placebo group at 24 weeks.

Body weight reduction was highest in the 6 mg/week UBT251 group at 24 weeks at 9.8% and lowest in the 2 mg/week group at 7.8%. In comparison, body weight reduction was 4.8% with semaglutide and 1.4% in the placebo group.

“Several cohort-specific factors warrant consideration when interpreting the magnitude of weight loss observed,” the authors wrote. “First, patients with type 2 diabetes mellitus typically achieve smaller magnitudes of weight reduction than those without diabetes … Second, the study was conducted exclusively in an Asian population, for whom lower body mass index thresholds are applied for defining overweight and obesity compared with Western populations, reflecting heightened cardiometabolic risk at lower body weights.”

Most adverse events were mild or moderate, but grade 3 or worse events occurred in 19% at 6 mg UBT251 versus 7.3% with semaglutide.

It’s hard to do a direct comparison, as the Phase III trials for retatrutide were bigger, had longer follow up, and were carried out in different countries, but in the type 2 diabetes Phase III trial for retatrutide the highest average HbA1c and body weight reductions were 2.0 points and 16.8%, respectively, over 40 weeks.

UBT251 definitely shows good HbA1c lowering ability compared with retatrutide and the weight loss at 24 weeks was also respectable. Whether it will help people reach the same body weight reduction as retatrutide over a longer period and in different populations remains to be seen.

Notably, in a separate Phase II trial looking at UBT251 as a treatment for obesity, UBT251 achieved up to 19.7% mean weight loss at 24 weeks at a final dose of 4 mg/week starting at 1 mg/week. Retatrutide produced 17.5% average body weight loss at 24 weeks at the highest dose available (12 mg/week) in its 2023 Phase II obesity trial, so it is possible that UBT251 can achieve similar results in the future for obesity but the two drugs would need to be trialed under similar conditions to get comparable results.