Co-formulation of Semaglutide and Cagrilintide Shows Promise Against Diabetes and Obesity

The modern era has seen an alarming rise in the prevalence of obesity and type 2 diabetes, conditions that have proven challenging to manage and are often linked by shared physiological mechanisms. Although lifestyle interventions such as diet and exercise remain cornerstones of treatment, pharmaceutical advancements are providing promising new options for individuals struggling with these chronic conditions. One such advancement is a co-formulation of semaglutide and cagrilinitide (CagriSema, Novo Nordisk) a novel drug combination currently in phase 3 clinical trials designed to address both weight loss and glycemic control in a way that is highly effective and manageable for patients.¹

Patient holding an injectable pen | Image credit: Orawan | stock.adobe.com

Cagrilintide is a long-acting amylin analog, whereas semaglutide is a well-known glucagon-like peptide-1 (GLP-1) receptor agonist. Both of these drugs act on different hormonal pathways to achieve significant effects on weight loss and blood glucose control. Together, they form a potent combination that may offer enhanced benefits over existing therapies.²

Amylin is a hormone co-secreted with insulin by the pancreas in response to food intake. It works by slowing gastric emptying, reducing food intake, and modulating postprandial glucose spikes. Cagrilintide, a synthetic analog of amylin, has been developed to produce these same effects while being more stable and long acting than the native hormone.

Meanwhile,GLP-1 (glucagon-like peptide-1) receptor agonists like semaglutide have been established as effective treatments for type 2 diabetes and, more recently, for obesity. By mimicking GLP-1, semaglutide increases insulin secretion, suppresses glucagon release, and slows gastric emptying, all of which contribute to better blood sugar control and weight loss.

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 already demonstrated a powerful impact on reducing hunger, and cagrilintide amplifies this effect, leading to an even greater reduction in food intake.

While semaglutide primarily aids in glucose control through increased insulin secretion and decreased glucagon, cagrilintide adds the benefit of modulating postprandial glucose levels through slower gastric emptying. This combination may help patients reach and maintain lower HbA1c levels more effectively than either drug alone.

Finally,amylin and GLP-1 work on separate but complementary pathways, allowing for a more holistic approach to metabolic health. This dual action on the gut-brain axis creates a more comprehensive impact on both glucose levels and weight management.

Patients taking CagriSema achieved significantly greater reductions in body weight and HbA1c levels. In fact, studies suggest that weight loss with CagriSema has a potential of up to 25%, positioning it as a game-changer in the field of obesity management.³ Furthermore, individuals with type 2 diabetes who took CagriSema showed improved hemoglobin A1c (HbA1c) reductions, often achieving levels well within the target range. These improvements suggest that CagriSema may be especially beneficial for those struggling to control both weight and blood sugar levels, offering a therapeutic option that addresses the root causes of metabolic disease.^2,3

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.

In terms of efficacy, the combination of cagrilintide and semaglutide appears to outperform GLP-1 receptor agonists alone, particularly for patients with higher baseline body weights or challenging glycemic profiles. This could lead to better long-term outcomes and lower risks of complications associated with diabetes and obesity.²

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.^1,2 It is essential for patients to work closely with their health care providers to monitor and manage any adverse effects to maintain treatment compliance and overall health.

CagriSema could be a future 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.

CagriSema’s arrival on the market may be a significant step forward in obesity and diabetes treatment. Its powerful combination of 2 complementary drugs offers a unique and effective tool for health care providers in managing complex metabolic disorders. The demand for such therapies will likely increase as obesity and diabetes prevalence continues to rise, and CagriSema may be poised to fill a critical gap.

The combination of cagrilintide and semaglutide in CagriSema represents an innovative approach to weight loss and diabetes management, offering patients a potentially more effective and convenient treatment option. Although more research will continue to refine its use and identify the best candidates for treatment, early evidence from the phase 3 trial suggests that CagriSema could be transformative in helping individuals achieve better health outcomes. As we look to the future of metabolic disease management, CagriSema stands as a promising addition to the therapeutic arsenal against diabetes and obesity, providing renewed hope for those in need.

References

1. A research study to see how well CagriSema compared to tirzepatide helps people with obesity lose weight. ClinicalTrials.gov. Updated August 20, 2024. Accessed November 26, 2024. https://clinicaltrials.gov/study/NCT06131437

2. Frias JP, Deenadayalan S, Erichsen L, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomized, double-blind, active controlled, phase 2 trial. The Lancet. 2023;402(10403):720-730. doi:10.1016/S0140-6736(23)01163-7

3. Fick M. Novo Nordisk affirms 25% weight-loss expectation for experimental drug CagriSema. Reuters. November 6, 2024. Accessed November 26, 2024. https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-says-its-experimental-drug-cagrisema-has-similar-side-effects-2024-11-06/