Combining an investigational agent, cagrilintide (Novo Nordisk), with semaglutide, a glucagon-like peptide-1 (GLP-1) agonist, results in better weight reduction than semaglutide alone in folks with a physique mass index (BMI) over 27 kg/m2, and the mix was well-tolerated, reveals a part 1 research.
The analysis was offered on the on-line ECO 2021 assembly by Lone Enebo, PhD, from Novo Nordisk, Denmark, and simultaneously published in The Lancet.
“Treatment with cagrilintide in any respect examined doses together with semaglutide 2.4 mg was typically well-tolerated with a suitable security profile,” say Enebo and coauthors, including that no obvious distinction was seen within the variety of opposed occasions throughout therapy teams.
“The information assist once-weekly dosing. The mixture of cagrilintide 1.2, 2.4, or 4.5 mg plus semaglutide 2.4 mg led to better weight reduction in contrast with semaglutide 2.4 mg solely.”
The once-weekly dosing routine was related to clinically significant weight lack of as much as 17.1% of physique weight with out life-style interventions.
“These information assist the additional scientific improvement of cagrilintide and semaglutide 2.4 mg as a possible novel and efficient mixture remedy for weight administration,” they add.
In an accompanying commentary, Sara Becerril, PhD candidate, and Gema Frühbeck, MD, from the University of Navarra, Pamplona, Spain, mentioned: “Approved pharmacological therapy choices [for overweight and obesity] are scarce and don’t satisfactorily bridge the hole in efficacy between life-style behavioral modifications and bariatric surgery to realize sustained long-term outcomes.”
But they emphasize: “Because the research was designed for security, the burden loss outcomes should be analyzed with warning. No life-style intervention was prescribed to supply weight reduction…Moreover, the protocol was amended to incorporate the very best cagrilintide dose, which could have been information pushed.”
Study Conducted in US
Semaglutide is presently accepted at a dose of 1.0 mg injected subcutaneously as soon as weekly for the therapy of type 2 diabetes, and as an oral agent for a similar indication. It is being developed for persistent weight administration at a dose of two.4 mg injected subcutaneously as soon as weekly. New drug purposes are beneath evaluation for the therapy of obesity by the US Food and Drug Administration, the European Medicines Agency, and different well being companies, with a choice on the US approval anticipated quickly.
The STEP trials, which have been printed in numerous journals over the previous 12 months, have established the efficacy and security of semaglutide 2.4 mg to deal with folks with weight problems.
For the present research, performed within the United States, 96 people, of whom 95 have been uncovered to therapy, aged 18-55 years with a BMI of 27.0-39.9 kg/m² who have been in any other case wholesome have been randomized to cagrilintide (0.16-2.4 mg, n = 12 in every group; 4.5 mg group, n = 11) or placebo (n = 24) together with semaglutide 2.4 mg. Mean age was 40.6 years, 59% of individuals have been males, and 54% have been Black or African American.
The 20-week trial included a 16-week escalation interval (the place individuals randomized to cagrilintide acquired progressively growing doses as much as the goal dose ranges) adopted by a 4-week therapy interval at goal dose (there have been six completely different goal dose ranges, one per cohort: 0.16, 0.3, 0.6, 1.2, 2.4, or 4.5 mg) and a 5-week follow-up. Participants, investigators, and sponsor have been all masked.
The main endpoint was variety of treatment-emergent opposed occasions from baseline to follow-up (finish of week 25).
No Clear Differences in Adverse Events Between Groups
Most opposed occasions reported have been gentle or reasonable in severity, and there have been no obvious variations between therapy teams: occasions have been reported in 69/71 individuals taking 0.16-4.5 mg cagrilintide and 23/24 on placebo.
Two extreme opposed occasions have been reported in two individuals, one with cagrilintide 1.2 mg together with semaglutide 2.4 mg (viral meningitis), and one within the pooled placebo together with semaglutide 2.4 mg group (serum creatinine improve). Both the occasions have been deemed unlikely to be associated to review therapy.
The commonest opposed occasions reported have been gastrointestinal issues in 77% of individuals, most continuously nausea in 56%, vomiting in 24%, and dyspepsia in 28%. On placebo, 79% of individuals skilled gastrointestinal occasions.
At week 20, imply share physique weight reductions from baseline have been better with cagrilintide 1.2 mg (15.7%) and a pair of.4 mg (17.1%) than for pooled placebo (9.8%).
Cagrilintide 4.5 mg led to a imply weight discount of 15.4% in contrast with 8.0% for placebo (each plus semaglutide).
“Mean physique weight reductions on this trial have been additionally better than these present in 26 weeks with cagrilintide alone (as much as 7.8% discount in physique weight relative to placebo with 4.5-mg dose),” add the authors, referring to earlier analysis.
Phase 3 Trial Program With Cagrilintide Is Planned
Enebo and coauthors clarify that cagrilintide is believed to have an effect on meals selections by focusing on each homeostatic and hedonic areas of the mind to induce satiety.
“Although each semaglutide and cagrilintide [both] induce satiety, they function in numerous areas of the mind, which could lead to an additive impact on urge for food regulation. Moreover, the potential for cagrilintide to have an effect on meals selections may contribute to the modification of consuming behaviors, additional bettering therapy efficacy.”
“Our information assist the additional scientific improvement of this drug mixture for weight administration. A part 3 trial program is now being deliberate to check cagrilintide together with semaglutide for weight administration,” they conclude.
Enebo is an worker and shareholder at Novo Nordisk. Becerril and Frühbeck have reported receiving grants from the Salud Carlos III Health Institute, CIBEROBN, and are cofunded by the European Union.
ECO 2021. Session AD12.04. Presented May 13, 2021.
Lancet. Published on-line April 22, 2021. Abstract
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