Triple agonist UBT251 lowered body weight over 24 weeks in a phase 2 trial

The study

UBT251 is a new drug that activates three receptors: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon. This phase 2 trial was multicentre, randomised, double-blind and placebo-controlled. It enrolled 205 adults with overweight or obesity who did not have type 2 diabetes. Of these, 59.0% were women, and participants were aged 18-61 years.

Participants received once-weekly UBT251 at 2 mg, 4 mg (with an initial dose of 0.5 mg or 1 mg) or 6 mg, or placebo, for 24 weeks. The primary endpoint was the percentage change in body weight at week 24. The trial is registered with the China Drug Trials Registry (CTR20250288) and ClinicalTrials.gov (NCT07177469).

What they found

Least-squares mean weight change at week 24 ranged from -19.7% to -13.6% across the UBT251 groups. With placebo it was -2.0%.

The placebo-adjusted differences ranged from -17.7% (95% CI -20.8% to -14.6%) to -11.5% (95% CI -14.1% to -9.0%). All comparisons had p < 0.001.

The abstract also reports improvements in waist circumference, body mass index, blood pressure, lipid profiles and glycaemic parameters. It gives no numbers for these. The most frequent adverse events were gastrointestinal symptoms, described as mild to moderate. The authors conclude that the safety profile was acceptable and that the results support phase 3 evaluation.

How much weight to give it

The design is strong for an early trial. It was randomised, double-blind and placebo-controlled, and the confidence intervals for the weight results are well away from zero.

There are clear limits.

• This is a phase 2 trial with 24 weeks of treatment. It cannot show how long the weight loss lasts, what happens after stopping, or long-term safety.
• Weight, waist, blood pressure, lipids and glycaemic measures are surrogate outcomes. The abstract reports no data on heart attacks, strokes or other clinical events.
• The abstract does not report how many people were in each group, how many stopped treatment, or the rates of specific adverse events. It also does not report funding, trial sites or participants' ethnicity.
• It does not say which dose gave which result within the weight range, so the dose-response pattern cannot be judged from the abstract.
• It does not compare UBT251 with another active drug. Cross-trial comparisons with other incretin drugs would not be reliable.
• The trial included only people without type 2 diabetes, so the results do not apply to people with it.

The word "acceptable" for safety is the authors' judgement. The full paper is needed to check the gastrointestinal events, any discontinuations and the safety of the glucagon-receptor component.

For your clinic

Nothing changes in practice now. UBT251 is still in clinical testing (the authors say the results support phase 3 evaluation), and this report gives no basis for prescribing or for individual treatment decisions.

This trial adds to evidence on multi-receptor agonists for weight loss. Doctors may wish to follow the phase 3 programme. Before drawing any conclusion, read the full paper for tolerability, dropout and safety data, plus the results in each dose group. Phase 3 data on longer follow-up and clinical outcomes will matter more than these 24-week results.

For patients who ask about new once-weekly weight-loss drugs, it is fair to say that this drug is still being tested, and that this one trial does not make it a treatment option.