Patients with obesity without diabetes who received once-weekly survodutide may experience greater reductions in body weight over 76 weeks compared with those who received placebo.
In the phase 3 SYNCHRONIZE-1 trial, researchers randomly assigned 725 patients at 116 sites in 14 countries to receive subcutaneous survodutide titrated to 3.6 mg, survodutide titrated to 6 mg, or placebo once weekly in addition to counseling on a reduced-calorie diet and physical activity. Eligible patients had a baseline body mass index (BMI) of at least 30 or a BMI of at least 27 with an obesity-related complication, excluding diabetes.
The primary endpoints were the percentage change in body weight from baseline and the proportion of patients achieving at least 5% weight loss at week 76. Key secondary endpoints included the percentage of patients achieving at least 10%, 15%, and 20% weight loss; the absolute change in body weight from baseline; as well as changes in waist circumference, systolic blood pressure, and eating behavior measures.
The researchers reported that mean body weight decreased by about 12% among the patients receiving survodutide 3.6 mg and by 13% among those receiving survodutide 6.0 mg compared with more than 5% among the patients receiving placebo. At week 76, 73% of the patients in the 3.6-mg group and 72% of those in the 6.0-mg group achieved at least 5% weight loss compared with 46% of those receiving placebo.
Higher proportions of patients receiving survodutide also achieved more substantial weight-loss thresholds. At least 10% weight loss was achieved by 55% and 57% of the patients in the 3.6-mg and 6.0-mg groups, respectively, compared with 26% of those receiving placebo. Weight loss of at least 15% occurred in 36% and 46% of patients receiving survodutide, respectively, compared with 12% of those receiving placebo. At least 20% weight loss was achieved by 25% and 29% of patients in the survodutide groups, respectively, compared with 7% of those in the placebo group.
The researchers also reported greater reductions in waist circumference among the patients receiving survodutide compared with among those receiving placebo. Additional improvements were observed in glycated hemoglobin, fasting plasma glucose, fasting insulin, triglycerides, and other lipid measures.
In a prespecified magnetic resonance imaging substudy involving 25 patients per treatment group, survodutide was associated with larger reductions in total fat volume, visceral fat volume, and liver fat content compared with placebo. Liver fat content decreased by 63% among the patients receiving survodutide 6.0 mg compared with 25% among patients receiving placebo.
The safety profile was characterized primarily by adverse gastrointestinal events. Nausea, vomiting, diarrhea, and constipation occurred more frequently among the patients receiving survodutide compared with among those receiving placebo and were most commonly reported during dose escalation. Gastrointestinal disorders were reported in 81% of the patients receiving survodutide 3.6 mg, 90% of those receiving survodutide 6.0 mg, and 48% of those receiving placebo. Discontinuation of study treatment because of adverse gastrointestinal events occurred in 18% and 20% of the patients receiving survodutide, respectively, compared with 3% of those receiving placebo. No mortality was reported during the trial.
The researchers noted several limitations. The study did not include an active comparator, preventing direct comparisons with currently available obesity drugs. A substantial proportion of the patients discontinued study treatment prior to week 76, and the trial excluded patients with diabetes, uncontrolled hypertension, recent adverse cardiovascular events, and inadequately controlled mood disorders. The researchers also noted that weight loss in the placebo group was greater than anticipated.
"In this trial, once-weekly survodutide led to significantly greater reductions in body weight than placebo in adults with obesity," wrote lead study author Carel W. le Roux, MB, ChB, PhD, of the University College Dublin School of Medicine, and colleagues.
The trial was funded by Boehringer Ingelheim. Full disclosures of the study authors can be found in the study.