Novo Nordisk reported phase 3 trial results showing that its investigational combination therapy CagriSema achieved greater reductions in blood sugar and body weight than injectable semaglutide in patients with type 2 diabetes. The company announced the findings on Feb. 2, noting that while the combination outperformed semaglutide, it did not meet the company’s previously stated target of 25% weight loss.
CagriSema is a once-weekly injectable therapy that combines semaglutide with cagrilintide, an experimental amylin receptor agonist. In the trial, patients receiving CagriSema experienced an average reduction in blood sugar of 1.91 percentage points from a baseline of 8.2% after 68 weeks. Average body weight declined by 14.2% over the same period. Patients treated with injectable semaglutide saw blood sugar reductions of 1.76 percentage points and weight loss of 10.2%.
“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, M.D., Ph.D., Novo Nordisk’s head of research and development, in a company release.
The phase 3 study enrolled 2,734 patients from multiple countries. Novo said it plans to present more detailed data from the trial later this year.
Novo has already submitted CagriSema to the U.S. Food and Drug Administration for approval in weight loss, based on results from two earlier phase 3 trials. In those studies, the combination therapy also failed to reach the company’s 25% weight-loss benchmark. One trial reported a weight reduction of 22.7%, while the second showed a decline of 15.7%, outcomes that contributed to a drop in the company’s share price at the time.
Investor reaction to the latest results was more muted. Novo’s shares fell from $59.43 at Friday’s close to $57.92 but rebounded to around $59 by 11:00 a.m. ET. Novo said it plans to approach the FDA to discuss a potential type 2 diabetes indication for CagriSema after results become available from two additional phase 3 trials, including one focused on cardiovascular outcomes and another comparing the therapy with placebo in patients with inadequately controlled diabetes.
Novo enrolled more than 2,700 patients with diabetes who were classified as overweight or obese based on body mass index. Participants were randomly assigned to receive weekly injections of CagriSema at two dose levels, Wegovy, cagrilintide, or placebo. The primary objective of the study was to evaluate blood sugar reduction with CagriSema compared with Wegovy, with weight loss assessed as a secondary endpoint.
Among patients who completed the 68-week trial on their assigned treatment, CagriSema reduced blood sugar by 1.9 percentage points and body weight by 14% from a baseline average weight of 101 kilograms. Wegovy reduced blood sugar by 1.8 percentage points and body weight by 10%. When all participants were included, regardless of treatment discontinuation or modification, CagriSema lowered blood sugar by 1.8 percentage points and weight by 13%, compared with 1.7 percentage points and 9% for Wegovy.
Novo said CagriSema showed side effects consistent with GLP-1–based therapies, including gastrointestinal symptoms such as nausea and vomiting that diminished over time.
CagriSema Shows Superior Phase 3 Outcomes vs Semaglutide
In the recent Phase 3 REIMAGINE 2 trial, CagriSema delivered greater blood sugar reduction and more significant weight loss than semaglutide alone in adults with inadequately controlled type 2 diabetes. The study, which followed participants for 68 weeks, found that CagriSema reduced HbA1c — a key blood sugar marker — more than semaglutide and also produced stronger body weight loss across treatment arms.
Greater Blood Sugar Control With CagriSema
The Phase 3 data showed that individuals receiving CagriSema achieved a larger average reduction in HbA1c — a primary measure of long‑term glucose control — compared with semaglutide at the same weekly dose. These results suggest that CagriSema’s dual‑mechanism design may offer enhanced glycemic control for adults with type 2 diabetes inadequately managed on current therapies.
