W. Timothy Garvey, M.D., served as lead author in the clinical trial.A new combination drug therapy is showing extraordinary promise in the bout against obesity, helping patients lose an average of 20 percent of their body weight in a major clinical trial.
The treatment, known as CagriSema, combines two hormone-based drugs — semaglutide, already approved for weight loss, and cagrilintide, which is still being studied. Cagrilintide is a long-acting form of amylin, which is normally secreted together with insulin from the pancreas, and for the first time is now being studied in a Phase 3 trial. Researchers say the combination has the potential to reshape the future of obesity treatment.
In a large Phase 3 clinical trial, led by the University of Alabama at Birmingham’s W. Timothy Garvey, M.D., and published this week in the New England Journal of Medicine, more than 3,400 adults without diabetes but considered obese or overweight and have at least one related health complication took part in a 68-week study. Participants were randomly assigned to receive either the drug combination, one of the two drugs alone, or a placebo, in addition to lifestyle counseling.
Patients who received CagriSema lost an average of 20.4 percent of their body weight in analyses similar to intention-to-treat and 22.7 percent weight loss in a completers’ type analysis, compared to just 3 percent in the placebo group. Those taking the combination were significantly more likely to hit major weight-loss milestones, such as losing 20-30 percent of their body weight.
While effective, the treatment was not without side effects. Participants experienced gastrointestinal side effects (nausea, vomiting, constipation) at rates comparable to that observed with semaglutide alone. These side effects were mostly mild or moderate and typically temporary.
Weight Loss Results (over 68 weeks):
• Cagrilintide–semaglutide group: 20.4 percent average weight loss
• Placebo group: 3 percent average weight loss
• Difference: 17.3 percentage points (statistically significant, P < 0.001)
Obesity affects more than 40 percent of adults in the United States, according to the Centers for Disease Control, and is linked to increased risk of heart disease, diabetes and cancer. While medications like semaglutide have already made headlines for their weight-loss benefits, this study suggests combining medications could push those results even further.
The findings could mark a significant step forward in medical weight management — especially for patients struggling to lose weight through diet and exercise alone.
Further research will be needed to confirm the long-term safety and cardiovascular effects of the combination drug. Still, experts say CagriSema could become a powerful new tool in the global effort to address obesity.
At UAB, Garvey holds the C. E. Butterworth, Jr., MD, Professorship in the Department of Nutrition Sciences, is a University Professor in the School of Health Professions and serves as the director of the UAB Diabetes Research Center.
Funding for this study was provided by Novo Nordisk. Learn more about the REDEFINE 1 ClinicalTrials.gov number, NCT05567796.