Novo unveils first data for 'triple G' agonist in diabetes

Novo Nordisk has reported the first mid-stage clinical data with its triple G agonist for diabetes in China, as it starts an international trials programme.

The drug candidate, UBT251, acts on GLP-1, GIP and glucagon receptors and is being jointly developed by Novo Nordisk and Chinese biopharma United Biotechnology for type 2 diabetes (T2D) and obesity. It works in a similar way to Eli Lilly's triple G drug retatrutide, which generated encouraging results in a phase 3 trial in T2D reported earlier this month.

In a phase 2 trial in Chinese people with T2D, UBT251 delivered a significant improvement in blood glucose control, measured using the haemoglobin A1c biomarker, with an average reduction of 2.16% after 24 weeks that improved on both placebo and Novo Nordisk's GLP-1 agonist Ozempic (semaglutide).

Patients taking the triple G also lost 9.8% of their starting body weight at that time point, which compared to a 1.4% reduction with placebo and 4.8% with Ozempic, which was given at a 1mg maintenance dose. Like Ozempic and retatrutide, UBT251 is administered as a once-weekly subcutaneous injection.

The HbA1c and weight-loss data were accompanied by positive effects on other secondary clinical endpoints, including waist circumference, blood pressure and lipids, according to Novo Nordisk. The study enrolled a total of 211 patients and investigated 2 mg, 4 mg, and 6mg weekly doses of UBT251.

United Biotechnology now plans to move ahead with two phase 3 trials of UBT251 in China, while Novo Nordisk said it will start an international phase 2 trial of the drug in T2D later this year. It is already running a 330-subject phase 1b/2a trial of the triple agonist for weight loss, which is due to read out in 2027.

Lilly's phase 3 TRANSCEND-T2D-1 trial of retatrutide showed that the drug reduced A1c levels between 1.7% and 2.0%, depending on the dose, with weight loss as a percentage of starting body weight ranging between 11.5% and 16.8% after 40 weeks of treatment. Novo's data looks to be in the right ballpark for efficacy, but it remains to be seen whether UBT251 will have a profile that can offset Lilly's long lead in the triple G category.

Analysts at Clarivate have suggested $30 billion-plus revenues are possible with retatrutide, on the grounds that its triple G mechanism combines reducing calorie intake and augmenting energy expenditure, representing an advance on the current generation of incretin-directed drugs for weight loss and T2D.

Lexicon candidate advances

Earlier this week, Novo Nordisk also started phase 1 testing of another obesity and diabetes candidate, Lexicon Pharma-partnered oral ACSL5 inhibitor LX9851, which does not act via incretin pathways. The trial is expected to be completed in the first quarter of 2027.

The drug is thought to work by delaying gastric emptying and suppressing appetite, leading to increased feelings of fullness, and was licensed by Lexicon to Novo Nordisk last year in a deal valued at up to $1 billion, including $75 million in upfront and near-term payments. The start of the phase 1 trial sparks a $10 million milestone payment.

Image by Alexander Lesnitsky from Pixabay