Share on PinterestNew combo drug from Novo Nordisk leads to more weight loss than semaglutide alone, according to late-stage trial findings. Image credit: Kristian Tuxen Ladegaard Berg/NurPhoto via Getty Images
- A new 68-week trial found that weekly injections with CagriSema resulted in weight loss of up to 14.2% compared with 10.2% for semaglutide (Wegovy).
- CagriSema also reduced HbA1C scores on average by 1.91%-points compared with 1.76%-points for semaglutide.
- This new drug is a fixed-dose combination of semaglutide and cagrilintide, an amylin receptor agonist.
GLP-1 medications have received a lot of publicity due in part to their use in treating obesity, though their initial use was for treating type 2 diabetes.
The name GLP-1 is short for glucagon-like peptide-1 receptor agonists. They work by mimicking the effects of a hormone that the intestine makes: glucagon-like peptide-1.
Glucagon-like peptide-1 can:
- stimulate insulin secretion around meal times
- decrease the secretion of glucagon, a hormone that raises blood sugar levels
- decrease how quickly the stomach empties, slowing digestion and the rise of blood sugar after eating
- create a sensation of stomach fullness that can reduce appetite and food intake.
These effects can make a difference for some people with type 2 diabetes or obesity who have found that other medical or lifestyle-based treatments have not helped.
Semaglutide is one such GLP-1, and is the active ingredient in Wegovy, Ozempic, and Rybelsus.
It is manufactured by Novo Nordisk, the pharmaceutical company behind a recent trial assessing the potential of a next-generation drug, CagriSema.
CagriSema combines semaglutide with another drug called cagrilintide, an amylin receptor agonist. This mimics the effects of the hormone amylin and can also slow down stomach emptying, decrease glucagon secretion after meals, and control appetite.
Novo Nordisk are currently running two research programmes to investigate the use of CagriSema in the treatment of type 2 diabetes and overweight and obesity.
Recently, the company has announced the latest results from the REIMAGINE 2 clinical trial for adults with type 2 diabetes investigating the effectiveness of CagriSema. Their findings have not yet appeared in a peer-reviewed journal.
What happened in the trial?
The REIMAGINE 2 trial ran for 68 weeks and involved a total of 2,728 participants with type 2 diabetes that was not adequately controlled by metformin.
Around 40% of the participants were also using an SLG2 inhibitor before the trial began. SLG2 inhibitors are a type of medication that causes the body to expel more glucose from the bloodstream into a person’s urine.
Participants received weekly doses of one of the following:
- CagriSema 2.4/2.4 milligrams (mg), meaning 2.4 mg of cagrilintide and 2.4 mg of semaglutide
- CagriSema 1 / 1 mg, or 1 mg of cagrilintide and 1 mg of semaglutide
- 2.4 mg of semaglutide
- 1 mg of semaglutide
- 2.4 mg of cagrilintide
- a placebo.
“As CagriSema is a fixed dose combination, it is a regulatory requirement to demonstrate that the combination is safe and effective for the target population and provides added benefit over the individual components,” a spokesperson for Novo Nordisk explained for Medical News Today.
“CagriSema 2.4/2.4 mg was therefore compared against the individual components: semaglutide 2.4 mg and cagrilintide 2.4 mg, respectively,” the spokesperson detailed.
Before beginning, the researchers measured the participants’ body weight and HbA1C results, an average blood sugar level to reflect the previous 2–3 months.
The mean baseline body weight was 101 kilograms (kg) and the mean baseline HbA1C score was 8.2%.
What were the key results?
The researchers found that after 68 weeks, if participants adhered to their treatment plan, the group taking CagriSema 2.4/2.4 mg had greater average changes in their body weight and HbA1C results than the group that just took 2.4 mg of semaglutide.
Specifically, the CagriSema 2.4/2.4 mg group had an average HbA1C reduction of 1.91%-points and weight loss of 14.2%, compared with the semaglutide 2.4 mg group’s average reductions of 1.76%-points and 10.2%, respectively.
When not looking at complete adherence to treatment plans, the researchers reported similar results.
Here, the CagriSema 2.4/2.4 mg group had an average HbA1C reduction of 1.80%-points and body weight reduction of 12.9%. For the semaglutide group, these averages were 1.68%-points and 9.2% respectively.
“By combining semaglutide and cagrilintide, we’re seeing superior outcomes in both blood glucose control and weight reduction beyond those achieved with each therapy individually,” said Martin Holst Lange, executive vice president, chief scientific officer, and head of Research and Development at Novo Nordisk in the company’s official announcement.
“The results strengthen our belief that CagriSema could be the first amylin-based combination therapy and a promising treatment option for individuals with type 2 diabetes, [which] also has a focus on weight loss,” said Holst Lange.
Novo Nordisk expects to present the full results of the trial at a scientific conference later this year.
MNT spoke to Mir Ali, MD, a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved with the study, about its findings.
“This trial indicates that there are more drugs on the horizon and more medication options will be available to patients,” Ali said.
“The thing to be aware of is that these are very early results done by the manufacturer,“ he cautioned. “It will require clinical trials by independent entities to delineate the true effectiveness and side effect profile of this and all new medications.”
What comes next for CagriSema?
Following the results of earlier trials, Novo Nordisk submitted a New Drug Application to the Food and Drug Administration (FDA) in December 2025 for the use of CagriSema to assist and maintain weight loss alongside diet and exercise adjustments.
Should it receive approval, this application would set the drug up to be used in the same cases as Wegovy.
In the meantime, Novo Nordisk has further trials ongoing for CagriSema. As well as further testing for type 2 diabetes, overweight, and obesity, they will also be seeing how its effectiveness and safety compare with tirzepatide (brand names Mounjaro, Zepbound).
“I think a better comparison would be this new medication versus tirzepatide,” Ali said to MNT. “[Tirzepatide] works on two hormone receptors and has been shown in clinical trials to be more effective than semaglutide.”
This comparison may have a lot riding on it given that tirzepatide is a drug manufactured by competitor Eli Lilly and Company.
Ali added that it was important to keep some perspective when looking at the results of this trial:
“The thing that people considering these medications should keep in mind is that these are tools to help change to a healthier diet and lifestyle. Studies also show that stopping these medications typically results in significant weight gain, so long-term treatment is likely necessary.”
