Triple agonist UBT251 lowers HbA1c in Chinese adults with type 2 diabetes in phase 2 trial

The study

This was a multicentre, randomised phase 2 trial published in Cell Metabolism. It enrolled 211 Chinese adults with type 2 diabetes. Mean age was 48.4 years, and 131 participants were male.

UBT251 is a triple agonist of the GLP-1, GIP and glucagon receptors. Participants received it once weekly by subcutaneous injection for 24 weeks. There were four UBT251 groups: 2 mg, 4 mg (initial dose 0.5 mg), 4 mg (initial dose 1 mg) and 6 mg. The two comparators were 1 mg semaglutide and placebo.

What they found

At week 24, HbA1c fell in every group. The figures below are least-squares mean changes.

• UBT251 groups: -2.16% (95% CI, -2.39 to -1.92) to -1.98% (95% CI, -2.31 to -1.64).
• Semaglutide: -1.77% (95% CI, -1.99 to -1.54).
• Placebo: -0.66% (95% CI, -0.90 to -0.41).

The placebo-adjusted differences for UBT251 ranged from -1.50% to -1.32% (all p < 0.001).

Compared with placebo, UBT251 also significantly reduced fasting blood glucose, 2-hour postprandial glucose and waist circumference (all p < 0.001).

Weight reduction with UBT251 was significantly greater than with placebo and with semaglutide (all p < 0.05). The abstract does not give the weight figures.

Gastrointestinal events were the most common treatment-emergent adverse events. The abstract does not report their rates, how severe they were, or how many people stopped treatment. It also does not report hypoglycaemia.

How much weight to give it

The authors say the findings support further phase 3 evaluation of UBT251.

This was a randomised trial, which supports the placebo comparisons. However, the abstract does not report blinding, dropouts or group sizes. Other limits:

• All participants were Chinese, so the results may not apply directly to Indian patients.
• The outcomes are surrogate markers (HbA1c, glucose, weight and waist circumference). The abstract reports no cardiovascular, kidney or other hard outcomes.
• Treatment lasted 24 weeks, so the abstract says nothing about durability or long-term safety.
• The abstract does not report funding.
• The abstract does not state whether HbA1c with UBT251 was formally tested against semaglutide. Only the weight comparison with semaglutide is reported as significant. The semaglutide dose was 1 mg, and the abstract does not report any other dose.
• The abstract does not report how the UBT251 doses compared with each other.

The full paper is needed to judge safety, tolerability and dose differences.

For your clinic

Nothing here changes practice. UBT251 was tested in a phase 2 trial, and this report gives no basis for any individual treatment decision.

In this trial, UBT251 lowered HbA1c, glucose and waist circumference versus placebo, and lowered weight versus placebo and semaglutide. The authors support further phase 3 evaluation. Hard outcomes, long-term safety and results in other populations have not yet been reported. Read the full paper, especially the adverse event tables, before drawing firm conclusions.