The co-formulation of semaglutide and cagrilintide, known as CagriSema, is demonstrating promising results in Phase 3 clinical trials for the treatment of type 2 diabetes and obesity. This novel drug combination, developed by Novo Nordisk, aims to address both weight loss and glycemic control through the synergistic action of its two components.
Mechanism of Action
Cagrilintide is a long-acting amylin analog that mimics the effects of amylin, a hormone co-secreted with insulin by the pancreas. It slows gastric emptying, reduces food intake, and modulates postprandial glucose spikes. Semaglutide, on the other hand, is a glucagon-like peptide-1 (GLP-1) receptor agonist that increases insulin secretion, suppresses glucagon release, and slows gastric emptying.
The combined effects of cagrilintide and semaglutide in CagriSema offer a dual approach to weight loss and glucose regulation. Both drugs influence appetite regulation in the brain, particularly within the hypothalamus. Semaglutide has demonstrated a powerful impact on reducing hunger, and cagrilintide amplifies this effect, leading to an even greater reduction in food intake.
Clinical Trial Data
Clinical trial data indicates that patients taking CagriSema achieved significantly greater reductions in body weight and HbA1c levels. Studies suggest that weight loss with CagriSema has the potential to reach up to 25%. Furthermore, individuals with type 2 diabetes who took CagriSema showed improved hemoglobin A1c (HbA1c) reductions, often achieving levels well within the target range.
A systemic review comparing semaglutide to other GLP-1 RAs and to CagriSema revealed that the combination product allowed for more weight loss, with patients losing nearly 14 kg. Study findings also hinted at improved glycemic control, with patients dropping nearly 1.8% in HbA1c at least 12 weeks post initiation.
Past phase 2 studies involved a comparison of the combination to its individual components, semaglutide and cagrilintide. The combination product allowed for a larger drop in HbA1c, about 2.18% over 32 weeks in people with T2D. The weight among participants decreased by 15.6%, and semaglutide showed a reduction of 5.1%.
Convenience and Adherence
One of the primary advantages of CagriSema is the convenience of a once-weekly injection, which improves patient adherence versus daily dosing. Furthermore, CagriSema’s dual mechanism means it could potentially replace multiple medications, simplifying treatment regimens for individuals who are often on numerous medications.
Adverse Effects
Although CagriSema is generally well tolerated, it is not without potential adverse effects. Gastrointestinal symptoms such as nausea, vomiting, and constipation are common, especially when starting the medication. These effects are consistent with those observed with GLP-1 receptor agonists and can usually be managed by gradually increasing the dose.
Potential Patient Populations
CagriSema could be a valuable option for adults with type 2 diabetes who need additional glycemic control beyond what GLP-1 receptor agonists alone can provide; those with obesity or those who have struggled to lose weight through lifestyle changes and other medications; and individuals with high cardiovascular risk since weight loss and improved glycemic control have favorable effects on cardiovascular outcomes.
Ongoing Research
Phase 3 trials are currently underway, with studies in larger populations and more varied patient characteristics. These trials will target primary outcomes like weight loss, T2D, and cardiovascular events over a time period of 4.5 years.
