On 28 March, at the American College of Cardiology (ACC) 75th Annual Scientific Session & Expo in New Orleans, Louisiana, results from a Bayesian network meta-analysis were presented comparing the efficacy and safety of CagriSema against its individual component, cagrilintide and semaglutide 2.4mg, in adults with overweight and obesity.
CagriSema is a fixed-dose, once-weekly subcutaneous combination of cagrilintide and semaglutide, acting as a Calcitonin Receptor (CALCR) agonist, glucagon-like peptide 1 receptor agonist (GLP-1RA), and receptor activity-modifying protein (RAMP) 1, 2, and 3 activator. It is currently in pre-registration for obesity and overweight in the US, in Phase III globally for obesity, overweight, and type 2 diabetes (T2D), and under Phase II investigation for metabolic dysfunction-associated steatohepatitis (MASH) and diabetic peripheral neuropathy.
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The Bayesian network meta-analysis drew on randomised controlled trial data from five databases, encompassing 2,803 adults with overweight or obesity, to assess the comparative efficacy, safety and tolerability of CagriSema, cagrilintide and semaglutide 2.4mg. The analysis aimed to define the optimal positioning of CagriSema relative to its monotherapy components.
The results of the meta-analysis confirmed that across all efficacy endpoints, including absolute and percentage weight loss, waist circumference, HbA1c reduction, fasting glucose and systolic blood pressure, CagriSema ranked first, semaglutide 2.4mg ranked second, and cagrilintide ranked third. On gastrointestinal (GI) tolerability, CagriSema ranked best for nausea, vomiting, diarrhoea and adverse events (AEs) leading to discontinuation. Cagrilintide ranked most favourably for allergic reactions and serious adverse events (SAEs), while semaglutide performed best for fatigue, neoplasms and CNS-related AEs.
Meta-analysis market implications
These findings support CagriSema as a first-line option for patients with obesity and/or T2D, offering the greatest weight loss and cardiometabolic improvements alongside the most favorable GI tolerability profile. Semaglutide 2.4mg remains a strong treatment option, while cagrilintide monotherapy represents a valuable alternative for patients with GLP-1RA GI intolerance or a preference for a more favorable SAE profile.
Key opinion leaders interviewed by GlobalData anticipate CagriSema’s potential to “cannibalise the semaglutide market”, adding that “it has weight loss similar to tirzepatide”.
All in all, CagriSema continues to strengthen its position in the overweight and obesity landscape. According to GlobalData’s Pharma Intelligence Center, there are 48 Phase III candidates, 109 Phase II candidates and 155 Phase I candidates for overweight and obesity globally.
