Survodutide induces up to 18.7% weight loss among adults with obesity in phase 2 trial
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Key takeaways:
- The majority of adults with obesity who received survodutide lost at least 10% of their body weight at 46 weeks.
- Weight loss peaked at 18.7% for adults receiving 4.8 mg suvodutide.
SAN DIEGO — Adults with overweight or obesity lost up to 18.7% of their body weight at 46 weeks with a glucagon/GLP-1 dual agonist, according to a speaker.
In data from a phase 2 trial presented at the American Diabetes Association Scientific Sessions, survodutide (Boehringer Ingelheim and Zealand Pharma) induced a greater weight loss than placebo at 46 weeks, and most participants receiving survodutide 3.6 mg or 4.8 mg lost more than 15% of their body weight.
“We are particularly impressed by the magnitude of weight loss benefit shown after 46 weeks of treatment with [survodutide],” Carel Le Roux, MD, PhD, professor of experimental pathology at the University College Dublin (UCD) School of Medicine and St. Vincent’s University Hospital, told Healio. “The efficacy seen suggests that this dual agonist mechanism of action, which adds glucagon receptor agonist activity, may have additive benefits to GLP-1 receptor agonists.”
Le Roux and colleagues conducted a randomized, double-blind, parallel group, placebo-controlled phase 2 trial enrolling 387 adults with a BMI of 27 kg/m2 or higher and a stable body weight at screening. Participants were randomly assigned, 1:1:1:1:1, to 0.6 mg, 2.4 mg, 3.6 mg or 4.8 mg survodutide or placebo for 46 weeks. Dose escalation took place during the first 20 weeks of the trial, followed by 26 weeks of dose maintenance. The primary endpoint of the study was the percent body weight change from baseline to 46 weeks. Secondary endpoints were the proportion of adults who achieved at least a 5%, 10%, 15% and 20% weight loss at 46 weeks. Researchers calculated outcomes for the planned treatment that participants were randomly assigned to and for the actual treatment dose participants received during the maintenance phase of the study. There were 88 adults who took 0.6 mg survodutide, 92 who received 2.4 mg, 71 who received 3.6 mg and 54 who received 4.8 mg.
Up to 18.7% weight loss observed at 46 weeks with survodutide
In the planned treatment analysis, the mean body weight loss among adults receiving survodutide was 6.2% in the 0.6 mg group, 12.5% in the 2.4 mg group, 13.2% in the 3.6 mg group and 14.9% in the 4.8 mg group compared with a 2.8% weight loss with placebo at 46 weeks (P < .05 for all). When outcomes were assessed for the actual treatment received, adults in the 0.6 mg survodutide group lost 6.8% of their body weight, the 2.4 mg group lost 13.6% of their body weight, the 3.6 mg group achieved a 16.7% body weight loss and the 4.8 mg lost 18.7% of their body weight compared with a 2% weight reduction with placebo (P < .01 for all).
In the planned treatment analysis, 65.5% of those randomly assigned to 2.4 mg survodutide, 65.6% in the 3.6 mg group and 68.8% in the 4.8 mg group achieved a 10% or greater weight loss at 46 weeks. A 20% or greater body weight reduction was observed for 20.7% of those in 2.4 mg survodutide group, 29.5% in the 3.6 mg group and 32.8% in the 4.8 mg group.
In the actual treatment analysis, the percentage of adults achieving a 10% or greater weight reduction was 79.1% with 2.4 mg survodutide, 82% with the 3.6 mg dose and 82.2% with the 4.8 mg dose. A 20% or greater body weight reduction was achieved by 25.6% of adults receiving 2.4 mg survodutide, 40% of those receiving 3.6 mg and 37.8% of adults in the 4.8 mg group.
Most gastrointestinal-related adverse events occur during dose escalation
Treatment-related adverse events occurred in 90.9% of adults receiving any dose of survodutide compared with 75.3% of adults receiving placebo. Gastrointestinal-related events were most common, with nausea, vomiting and diarrhea the most commonly reported symptoms. Two serious adverse events that were related to the medication were reported, both occurring in the 3.6 mg survodutide group.
“Many, if not most of our side effects occurred in the rapid dose titration phase that happened over 20 weeks, which of course is a necessity in a phase 2 trial,” Le Roux said during a presentation. “We all live and learn, and we’ll be able to adjust [dose escalation] as time goes on.”
During the press conference, Le Roux said studies have not yet been conducted comparing survodutide with semaglutide (Ozempic/Rybelsus/Wegovy, Novo Nordisk) or other medications, but he said the new agent could play a role alongside other dual agonists.
“What we see with all of this class of drugs, we are actually able to get to this 15% to 20% weight loss,” Le Roux said. “That’s very encouraging that we have so many assets now.”
Le Roux also said that body composition would be analyzed in future, phase 3 trials.
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Le Roux C, et al. 51-OR. Presented at: American Diabetes Association Scientific Sessions; June 23-26, 2023; San Diego.
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