Survodutide leads to striking weight loss in people who are overweight or obese: Phase II trial
USA: A Phase II study has shown superior efficacy of survodutide versus placebo in people with obesity or overweight without type 2 diabetes following 46 weeks of treatment. The findings were presented at the 83rd Scientific Sessions of the American Diabetes Association (ADA) in San Diego, CA, U.S.
The study revealed that about 40% of people who reached the highest two doses of survodutide (BI 456906) achieved a weight loss of at least 20%.
Survodutide, a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist is being developed by Boehringer Ingelheim and Zealand Pharma to treat obesity and non-alcoholic fatty liver disease. Survodutide has received US FDA (Food and Drug Administration) Fast Track Designation for patients with NASH. Currently, the drug is being evaluated in a Phase 2 study in adults with NASH and stages F1/F2/F3 liver fibrosis, with trial completion expected in the last quarter of 2023.
The mechanism of action is that GLP-1 receptor agonism inhibits appetite and glucagon receptor agonism increases energy expenditure, helping to treat the disease of obesity.
Carel Le Roux and the team reported, "The trial showed a "striking" and clear dose-response regarding weight loss, with no new, unexpected safety signals."
The study included 387 adults aged 18 to 75 with body mass index (BMI) ≥ 27 kg/m2 (obesity or overweight) without type 2 diabetes at sites in North America, Australia/New Zealand, Europe, and Asia. The patients' median age was 49, with a body weight of 106 kg and a BMI of 37 kg/m2, and 68% were women.
They were randomized to receive a planned weekly subcutaneous maintenance survodutide dose of 0.6 mg (n=76), 2.4 mg (n=78), 3.6 mg (n=76), 4.8 mg (n=76), or placebo (n=77). During a 20-week dose-escalation phase, the dose escalated rapidly (monthly), followed by a 26-week maintenance phase. Patients who did not reach the planned dose remained on a lower dose during the maintenance phase.
During the maintenance phase, 88 patients took 0.6 mg of survodutide, 92 took 2.4 mg of survodutide, 71 took 3.6 mg of survodutide, 54 took 4.8 mg of survodutide, and 76 took a placebo. All were given as weekly subcutaneous injections.
The percentage change in body weight from baseline to week 46 was determined (primary outcome). Secondary outcomes were the percentage of patients who reached a body weight reduction of ≥ 5%, ≥ 10%, and ≥ 15% from baseline to week 46.
The authors reported the following findings:
· Mean weight loss at 46 weeks in the planned treatment analysis (where some patients in each group were taking a lower than planned dose during maintenance) was 6.2% in the 0.6-mg survodutide group, 12.5% in the 2.4-mg group, 13.2% in the 3.6-mg group, 14.9% in the 4.8-mg group, and 2.8% in the placebo group.
· Among participants who did reach and stayed on their assigned dose during the maintenance phase, average weight loss was 6.8% in the 0.6-mg survodutide group,13.6% with 2.4 mg survodutide,16.7% with 3.6 mg survodutide, 18.6% with 4.8 mg survodutide, and 2.0% with placebo.
· Patients reaching and staying on a weekly subcutaneous dose of 4.8 mg survodutide lost 18.6% of their body weight at 46 weeks.
· In terms of secondary outcomes, in the group of patients with a planned weekly dose of 4.8 mg survodutide, 83%, 69%, and 55% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
· In the group of patients with an actual weekly dose of 4.8 mg survodutide, 98%, 82%, and 67% attained weight loss of ≥ 5%, ≥ 10%, and ≥ 15% of their initial weight, respectively, at 46 weeks.
· 33% of patients in the group with a planned weekly dose of 4.8 mg survodutide and 38% of patients with an actual weekly dose of 4.8 mg survodutide lost ≥ 20% of their baseline body weight by week 46.
· Adverse events occurred in 91% of patients in the survodutide groups and 75% in the placebo group.
· The most common side effects were nausea, vomiting, diarrhoea, and constipation, which were primarily mild to moderate and mainly occurred during dose escalation. These effects may potentially be mitigated by more gradual dose escalation.
· There were no unexpected safety or tolerability concerns or Ydrug-related severe adverse events.
"These "encouraging data" support further study of survodutide for weight loss in larger Phase 3 trials," the authors concluded.
