On 12 May 2026, at the 33rd European Congress on Obesity in Istanbul, Türkiye, findings from the Phase 3a REDEFINE-1 trial (NCT05567796) were presented, assessing Novo Nordisk’s fixed-dose combination of cagrilintide 2.4mg and semaglutide 2.4mg (CagriSema) in adults with obesity, defined as a BMI of ≥30kg/m² or ≥27 kg/m² with one or more obesity-related complications. While modern pharmacotherapy for obesity has achieved substantial weight loss, there is a recognised risk of concomitant muscle mass loss, with potential implications for physical function and the development of sarcopenia. This analysis aimed to evaluate muscle strength, changes in body composition assessed by dual-energy X-ray absorptiometry (DXA), and the correlation between body composition and physical function.
CagriSema is a fixed-dose, once-weekly subcutaneous co-formulation of cagrilintide (a long-acting amylin analogue acting at the calcitonin receptor) and semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA). It is currently in pre-registration for obesity and overweight in the US, in Phase III investigation globally for obesity, overweight, and type 2 diabetes (T2D), and under Phase II evaluation for metabolic dysfunction-associated steatohepatitis (MASH) and diabetic peripheral neuropathy.
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The study was conducted as a 68-week, randomised, double-blind, placebo- and active-controlled, multi-centre trial in which 3,417 participants were randomised in a 21:3:3:7 ratio to once-weekly subcutaneous CagriSema 2.4mg/2.4mg, semaglutide 2.4mg, cagrilintide 2.4mg, or placebo, each as an adjunct to a reduced-calorie diet and increased physical activity. The sit-to-stand (STS) test was used to assess muscle strength at baseline and week 68 in 1,038 participants. Of these, 252 also underwent DXA to assess body composition, providing measurements of bone, fat mass, and lean soft tissue (LST). A post-hoc analysis was conducted to assess the correlation between body composition and physical function scores from the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT) and SF-36v2 Health Survey Acute (SF-36v2) questionnaires. All results are reported for the trial product estimate.
In results presented at ECO 2026 by Eric Ravussin, PhD, Professor of diabetes and metabolism and director of the Human Translational Physiology Laboratory and Nutrition Obesity Research Center at Pennington Biomedical Research Center, Baton Rouge, Louisiana, CagriSema 2.4mg / 2.4mg achieved the greatest weight reduction at week 68 in the DXA subgroup (−23.9%), compared with semaglutide 2.4mg (−16.6%), cagrilintide 2.4mg (−15.0%), and placebo (−2.8%). Weight loss with CagriSema was predominantly driven by fat mass reduction: 66.9% of the weight lost was attributable to fat mass and 33.1% to lean soft tissue. This pattern was consistent across all active treatment arms: fat mass accounted for 69.7% of weight loss with semaglutide and 62.9% with cagrilintide. Notably, in CagriSema-treated participants who achieved ≥30% body weight loss, the proportion of fat mass declined from 46.3% to 33.2%, while the LST proportion increased from 51.3% to 63.2%, confirming an improvement in body composition at higher levels of weight loss. Furthermore, CagriSema significantly improved physical function versus placebo on both the IWQoL-Lite-CT and SF-36v2 patient-reported outcome measures, and did not decrease muscle strength relative to placebo.
Key opinion leaders interviewed by GlobalData have noted CagriSema’s potential to compete directly with semaglutide and achieve weight loss comparable to tirzepatide, suggesting it could meaningfully reshape competitive dynamics within the obesity market.
While an overall absolute reduction in lean soft tissue was observed with CagriSema, the proportion of lean soft tissue increased following weight loss, and muscle strength was preserved. Together, these findings reinforce CagriSema’s potential as a promising dual-mechanism therapy capable of delivering substantial, fat-predominant weight loss with maintained physical function, continuing to strengthen its position in the overweight and obesity landscape. According to GlobalData’s Pharma Intelligence Center, there are currently 48 Phase III candidates, 112 Phase II candidates, and 158 Phase I candidates for overweight and obesity in development globally.
