Cagrilintide, semaglutide combination warrants further investigation for weight loss
medwireNews: Phase 1 trial results published in The Lancet suggest that combination treatment with the long-acting amylin analog cagrilintide plus high-dose semaglutide is well tolerated and may be a feasible treatment option for obesity.
Lone Enebo (Novo Nordisk A/S, Søborg, Denmark) and co-investigators explain that currently approved nonsurgical weight-loss treatments result in an average weight loss of 3–9% compared with placebo, “which might not be sufficient for improvements in some obesity-associated complications,” and suggest that combining drugs with different mechanisms of action could provide more effective options.
The 20-week dose-escalation study included 95 people aged 18–55 years with a BMI of 27.0−39.9 kg/m² and no other health conditions who were randomly assigned to receive once-weekly treatment with cagrilintide at one of six doses (range 0.16–4.5 mg) or placebo alongside semaglutide 2.4 mg/week, without any lifestyle intervention. Both cagrilintide and semaglutide were given subcutaneously, and doses were co-escalated in 4-week intervals to the final dose over a 16-week period.
Enebo and team report that the combination treatment was “generally well tolerated,” and “no unexpected safety concerns were identified in the trial.” The proportion of participants with adverse events (AEs) with cagrilintide plus semaglutide ranged from 92% for the cagrilintide 0.16 mg group to 100% for the cagrilintide 2.40 mg group, while 96% of those given placebo plus semaglutide experienced AEs.
“Most adverse events reported were mild or moderate in severity, with no apparent differences between treatment groups,” say the researchers. They note that the most frequently reported AEs were gastrointestinal (77%), most commonly nausea, vomiting, and dyspepsia.
In the pharmacokinetic analysis, Enebo et al found that cagrilintide had an elimination half-life of approximately 7–8 days, with maximum exposure at 24–25 hours after administration, “making it suitable for once-weekly dosing.” Moreover, semaglutide elimination and exposure were not impacted by concomitant cagrilintide use, they add, “supporting further clinical development of the cagrilintide and semaglutide 2.4 mg combination for weight management.”
In an exploratory efficacy analysis, the average reduction in bodyweight over 20 weeks was significantly greater among participants treated with cagrilintide 1.2–4.5 mg versus placebo, with the greatest reduction seen among those given the 2.4 mg dose, at 17.1%.
Noting that in the previously published phase 3 STEP 1 trial, treatment with semaglutide 2.4 mg resulted in a significant average weight loss of 12.4% over 68 weeks relative to placebo, Enebo and team say that “the combination of cagrilintide with semaglutide 2.4 mg has the potential to further close the gap between the available pharmacological options for weight management and bariatric surgery.”
They caution, however, that the exploratory weight loss data in their phase 1 trial “should be interpreted with caution,” and that “[l]onger trials are needed to fully assess the efficacy and safety of this treatment combination and assess whether weight loss is sustained.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group