A triple dose of Novo Nordisk’s GLP-1 agonist Wegovy has shown improved activity on weight loss in an obesity trial, as the drugmaker tries to fend off a marketplace challenge from Eli Lilly.
A 7.2mg weekly injection of semaglutide achieved an 18.7% reduction in body weight after 72 weeks in the STEP UP trial, just published in The Lancet Diabetes & Endocrinology, which involved adults with a body mass index (BMI) of 30 kg/m2 or greater, without diabetes. Those receiving the current 2.4mg dose – sold as Wegovy – saw a 15.6% reduction while the placebo group shed 3.9% of their weight.
An accompanying study of the high dose in adults with a BMI of 30 or more and type 2 diabetes, STEP UP T2D, has also been published in the journal and showed weight loss at 72 weeks of 13.2% versus 9.3% with placebo, with no significant improvement over the standard dose of the drug.
The higher dose was associated with more side effects than the regular dose in both studies, mainly gastrointestinal upset that is linked to the GLP-1’s mode of action.
However, the stronger version could be a useful addition to the anti-obesity armamentarium, according to Dr Simon Cork, a physiology expert at Anglia Ruskin University (ARU) in the UK, who was not involved in the trials.
“Interestingly…twice as many patients (33% vs 16%) lost over 25% of their body weight on higher dose semaglutide compared to lower dose,” he said. “This suggests that patients with higher body mass, who would benefit most from more substantial weight loss, may benefit more from high-dose semaglutide than that which is currently available.”
The data have been finalised as Novo Nordisk is feeling the effects of competition from Lilly and its dual GIP/GLP-1 agonist Zepbound (tirzepatide), which has been shown to be more effective at cutting weight than Wegovy in head-to-head trials, and as both brands are being widely copied by compounding pharmacies.
Last week, Novo Nordisk announced that it was cutting 9,000 jobs – more than 11% of its total workforce – blaming competition in the obesity category that fuelled stellar growth for the group before momentum started to be lost this year.
High-dose semaglutide is just one way that Novo Nordisk is hoping to recapture some of its former growth in the obesity category, along with a daily oral 25mg formulation of semaglutide, subcutaneous and oral dual GLP-1 and amylin agonist amycretin, and CagriSema, a combination of amylin agonist cagrilintide and semaglutide.
Semaglutide 7.2mg has already been submitted for approval, while the other three projects are in late-stage development.
Lilly, meanwhile, is developing an oral GLP-1 agonist called orforglipron in phase 3 and expects to report results from a head-to-head trial against oral semaglutide next year. Clinical results to date seem to give an edge to Novo Nordisk’s oral candidate, although both have shown lower activity on weight than the current generation of weekly injectables.
It is also running phase 3 studies of retatrutide, a triple agonist of GIP, GLP-1, and glucagon that is being developed simultaneously for obesity, osteoarthritis, and obstructive sleep apnoea, with follow-up studies in diabetes and chronic lower back pain.
