The U.S. Food and Drug Administration is expected to issue its decision before the close of 2026 on whether to grant approval to CagriSema, Novo Nordisk’s investigational once-weekly injectable that pairs cagrilintide with semaglutide for chronic weight management. Novo Nordisk filed the New Drug Application in December 2025, proposing use together with a reduced-calorie diet and increased physical activity in adults who are obese or who are overweight and have at least one weight-related comorbid condition.
If the agency signs off, the product would become the first subcutaneous therapy that merges a glucagon-like peptide-1 (GLP-1) receptor agonist with an amylin analogue for this indication. The submission leans heavily on data from two phase 3 studies—REDEFINE 1 and REDEFINE 2—together enrolling roughly 4,600 participants who met the trial’s overweight or obesity criteria.
CagriSema’s Mechanism of Action
CagriSema combines cagrilintide, a long-acting amylin analogue, with semaglutide, a GLP-1 receptor agonist already marketed under the name Wegovy for chronic weight management. By hitting two complementary pathways that influence appetite, satiety, and overall energy intake, the drug aims to produce greater weight loss than either component alone.
Amylin is a pancreatic hormone released alongside insulin when food enters the gut; it helps signal fullness and assists in regulating blood-sugar levels. GLP-1 receptor activation, on the other hand, curtails hunger and reduces caloric consumption. Delivering both signals in a single weekly injection simplifies the regimen for patients.
Evidence Behind the FDA Submission
The regulatory package includes two key phase 3 trials. REDEFINE 1 recruited adults without diabetes who carried obesity or overweight status together with at least one related health complication. A total of 3,417 participants were screened and randomized.
At week 68, the study estimated a mean weight reduction of 20.4% for those receiving CagriSema, compared with a 3.0% decline in the placebo arm when analyzed with the treatment-policy estimand. Using the trial-product estimand, the average loss rose to 22.7% versus 2.3% for placebo.
REDEFINE 2 focused on 1,206 adults who had type 2 diabetes in addition to obesity or overweight. The same 68-week endpoint showed an estimated mean loss of 15.7% for the active group, while the control group experienced a modest decline of 3.1%.
The safety profile was driven largely by gastrointestinal adverse events (AEs), consistent with the known effects of GLP-1–based therapies and earlier experience with cagrilintide. Nausea, vomiting, diarrhea, constipation, and abdominal pain were among the most commonly reported events, and most were mild to moderate in severity.
In the REDEFINE 1 trial, 5.9% of participants on CagriSema stopped treatment because of adverse events, whereas 3.5% of those receiving placebo did the same. The diabetes-focused study observed a comparable discontinuation rate of 8.4% for the active arm and a low figure for the placebo group.
A cardiovascular outcomes study, designated REDEFINE 3, is underway and is slated to release its results in the latter half of 2027. This trial will evaluate the drug’s impact on major heart-related events, an important consideration for a medication intended for long-term use.
According to the company, an FDA decision is anticipated by the end of 2026. Should approval be granted, CagriSema will be administered via a once-weekly subcutaneous injection, with a target dose of 2.4 mg of each component.
The application emphasizes that the medication is to be used as part of a full weight-management plan that includes dietary modification and increased physical activity, reflecting standard practice in obesity treatment.
