CagriSema delivered 12.4% weight loss versus 9.1% with tirzepatide 5 mg in REIMAGINE 5, with non-inferior HbA1c reduction in type 2 diabetes.
Written By: Khushi Patel, PharmD
Reviewed By: Pharmacally Editorial Team
Novo Nordisk’s investigational once-weekly CagriSema produced greater weight loss than tirzepatide 5 mg in adults with type 2 diabetes in the phase 3 REIMAGINE 5 trial (NCT06534411), while achieving a non-inferior reduction in HbA1c. In the separate phase 3 REDEFINE 9 study (NCT06388187), CagriSema reduced body weight by 21.0% versus 2.0% with placebo in adults with overweight or obesity.
CagriSema Delivered Greater Weight Loss Than Tirzepatide 5 mg
REIMAGINE 5 evaluated once-weekly CagriSema 1.0 mg/1.0 mg against tirzepatide 5 mg in adults with type 2 diabetes whose disease remained inadequately controlled on metformin, an SGLT2 inhibitor, or both. The trial had dual primary endpoints assessing change in HbA1c and relative change in body weight from baseline to week 60.
At week 60, estimated average weight loss reached 12.4% with CagriSema versus 9.1% with tirzepatide 5 mg, meeting the prespecified superiority endpoint for weight loss. CagriSema also reduced HbA1c by 1.71 percentage points, compared with 1.67 percentage points for tirzepatide 5 mg, meeting the criterion for non-inferiority.
The findings establish the reported comparison specifically against the 5 mg tirzepatide dose evaluated in REIMAGINE 5 and should not be generalized to other tirzepatide doses based on these topline results.
21% Weight Reduction in Adults with Overweight or Obesity
REDEFINE 9 evaluated CagriSema as an adjunct to a reduced-calorie diet and increased physical activity in adults living with overweight or obesity. The phase 3 study included CagriSema 1.7 mg/1.7 mg and 1.0 mg/1.0 mg treatment groups compared with placebo.
At week 68, CagriSema 1.0 mg/1.0 mg produced a 21.0% reduction in body weight versus 2.0% with placebo, meeting the primary superiority endpoint. The combination also showed greater improvements than placebo in prespecified supportive measures, including systolic blood pressure, waist-to-height ratio and fasting lipid profile.
The study’s primary endpoints included relative change in body weight and the proportion of participants achieving at least 5% weight reduction from baseline.
Combining Amylin and GLP-1 Pathways
CagriSema is a fixed-dose combination of cagrilintide, a long-acting amylin receptor agonist, and semaglutide, a GLP-1 receptor agonist. Novo Nordisk is evaluating the once-weekly subcutaneous therapy in adults with overweight or obesity through the REDEFINE program and in type 2 diabetes through the REIMAGINE program.
The new results add clinical evidence for combining these two biological pathways and provide data from different treatment settings, including weight management and glycemic control.
Topline Safety Data Do Not Include Detailed Adverse-Event Rates
Novo Nordisk reported that CagriSema was well tolerated overall in both trials, with a safety profile consistent with previous studies.
However, the topline release does not provide detailed incidence rates for individual adverse events, including specific gastrointestinal events such as nausea or vomiting. A more complete assessment of tolerability will therefore require the detailed trial safety dataset and subsequent clinical reporting.
FDA Decision Expected in Q4 2026
CagriSema remains investigational. Novo Nordisk submitted a New Drug Application to the U.S. FDA in December 2025 for weight management, with a regulatory decision expected in Q4 2026.
The REIMAGINE 5 and REDEFINE 9 results add phase 3 evidence to CagriSema’s development program, with the REIMAGINE 5 data providing a direct comparison with tirzepatide 5 mg and the REDEFINE 9 findings demonstrating substantial weight reduction versus placebo.
Reference
Novo’s CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial, Novo Nordisk, 21 September 2026
A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Tirzepatide in People With Type 2 Diabetes Treated With Metformin, SGLT2 Inhibitor or Both (REIMAGINE 5), ClinicalTrials.gov ID NCT06534411
A Research Study to See How Well Different Doses of CagriSema Help People With Excess Body Weight Lose Weight, ClinicalTrials.gov ID NCT06388187
About the Writer
Khushi Patel is a Pharm.D (Linkedin) professional with a strong foundation in clinical pharmacy, patient-centered care, regulatory affairs, and pharmacovigilance, with published work on Brugada syndrome.
Her interests include regulatory affairs, pharmacovigilance, guideline integration, multimodal therapy, pharmacogenomics, and antibiogram utilization, with a focus on evidence-based clinical decision-making and medication safety.
As a Pharmacally healthcare writer, she translates clinical and scientific evidence into clear, accurate, and clinically relevant healthcare content, while continuously developing her expertise in evolving pharmacy practice.