Adding an investigational long-acting amylin analogue to semaglutide was each protected and efficient for weight administration, in keeping with a section Ib randomized managed trial.
Of six totally different doses of once-weekly subcutaneous cagrilintide (AM833) examined, sure doses plus 2.4 mg of the GLP-1 receptor agonist semaglutide resulted in considerably larger weight reduction in contrast with semaglutide alone, reported Lone B. Enebo, PhD, of Novo Nordisk in Søborg, Denmark, and colleagues.
The findings had been introduced on the digital European Congress on Obesity and likewise revealed in The Lancet.
Specifically, the researchers discovered that three doses of cagrilintide — 1.2 mg, 2.4 mg, and 4.5 mg — along with once-weekly subcutaneous 2.4-mg semaglutide yielded vital weight reduction from baseline by the top of remedy (week 20):
- 1.2-mg cagrilintide: 15.7% drop in physique weight from baseline
- 2.4-mg cagrilintide: 17.1% drop
- 4.5-mg cagrilintide: 15.4% drop
In comparability with placebo plus semaglutide, 1.2 mg, 2.4 mg, and 4.5 mg of cagrilintide plus semaglutide all resulted in considerably larger estimated remedy variations for change in baseline physique weight.
Doses of 0.16 mg (8.3% drop in baseline physique weight), 0.30 mg (10% drop), and 0.60 mg (10.6% drop) of cagrilintide plus 2.4-mg semaglutide all yielded barely larger drops in baseline physique weight versus placebo plus semaglutide, though the variations weren’t statistically considerably.
Across the board, glycemic parameters confirmed enchancment in all remedy teams whatever the cagrilintide dose.
These findings constructed upon a earlier phase II monotherapy trial, initially introduced on the 2020 virtual ObesityWeek, which met its main endpoint displaying a ten.8% weight reduction at week 26 with 4.5-mg cagrilintide in contrast with a 3% weight reduction with placebo.
Novo Nordisk additionally just lately revealed findings of the STEP clinical program, demonstrating that once-weekly 2.4-mg semaglutide plus life-style administration resulted in a major drop in physique weight after 68 weeks of remedy versus life-style intervention alone.
This dose of semaglutide has but to be FDA permitted, though Novo Nordisk filed for approval in December 2020. In December 2017, the agent was first permitted in 0.5-mg and 1-mg injectable dosing bought below the commerce identify Ozempic, which is indicated for sort 2 diabetes and danger discount of main cardiovascular occasions, together with coronary heart assault, stroke, and dying, in adults with sort 2 diabetes with identified coronary heart illness. Subsequently, in September 2019, an oral type of semaglutide was permitted in 7-mg and 14-mg tablets, bought below the commerce identify Rybelsus, likewise indicated for sort 2 diabetes.
Cagrilintide works as a long-acting acylated amylin analogue that has agonistic results on amylin and calcitonin receptors. Amylin is a glucoregulatory pancreatic hormone that is secreted together with insulin, concerned in delaying of gastric emptying, in addition to suppressing the discharge of postprandial glucagon.
This trial recruited 285 adults ages 18 to 55 with a physique mass index of 27 to 39.9 from the Altasciences Clinical Kansas web site in Overland Park. Of this group, 96 had been randomly assigned to remedy, averaging about 16 members in every of the six cohorts. Using a 3:1 randomization, a median of 12 members had been assigned to every of the six cagrilintide plus semaglutide teams, with every group in contrast with six totally different teams of 4 members assigned to placebo plus semaglutide.
The six teams receiving cagrilintide had been began on preliminary doses of 0.01, 0.02, 0.04, 0.08, 0.16, and 0.45 mg every, which had been escalated each 4 weeks till remaining doses had been achieved by week 16. Cagrilintide and placebo had been administered through a NovoPen4 sturdy gadget on the fitting aspect of the stomach, whereas semaglutide was administered with a PDS290 pre-filled pen-injector on the left aspect.
The trial didn’t embody any life-style intervention, and members had been instructed to keep up their typical stage of bodily exercise all through the trial.
As for security, mixture remedy was typically effectively tolerated. As anticipated with a GLP-1 receptor agonist, nearly all of treatment-related opposed occasions had been gastrointestinal issues, together with nausea, decreased urge for food, vomiting, dyspepsia, and diarrhea. Among the 566 treatment-emergent opposed occasions reported, 207 had been gastrointestinal-related, evenly unfold throughout cagrilintide doses.
Overall, nearly all of opposed occasions had been delicate or reasonable, and solely two members within the mixture remedy group skilled occasions resulting in withdrawal.
“The key level with combos is the must be simpler than monotherapy at an affordable worth when it comes to each opposed occasions and value,” identified Sara Becerril, PhD, and Gema Frühbeck, MD, PhD, each of the University of Navarra in Pamplona, Spain, in an accompanying commentary.
Because this section Ib trial was primarily designed for security, the burden loss efficacy findings ought to be interpreted “with warning,” they famous.
Ultimately, any lingering efficacy questions will solely be answered with extra long-term trials.
Disclosures
The trial was funded by Novo Nordisk A/S.
Enebo and different co-authors reported employment with Novo Nordisk.
Becerril and Frühbeck reported relationships with the Spanish Health Institute Instituto de Salud Carlos III and CIBEROBN, and are co-funded by the European Union.
