CagriSema Research & Studies

Obesity remains a major global health challenge, driving demand for effective pharmacotherapies. Cagrilintide, a once-weekly amylin receptor agonist, and its fixed-dose combination with semaglutide (CagriSema) represent novel therapeutic approaches. This systematic review and meta-analysis evaluated their efficacy and safety in adults with overweight or obesity.

Cagrilintide-semaglutide (CagriSema) is a fixed-dose combination of the amylin receptor agonist cagrilintide and the glucagon-like peptide-1 receptor agonist semaglutide administered subcutaneously once weekly. CagriSema has demonstrated significant weight reduction and improved glycemic control in participants with excess adiposity and type 2 diabetes (T2D).

To evaluate the efficacy and safety of CagriSema, a fixed-dose combination of cagrilintide, a long-acting amylin analogue, and semaglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, compared with placebo, cagrilintide, or semaglutide monotherapy in overweight or obese individuals. A systematic review and meta-analysis was conducted in accordance with PRISMA and Cochrane guidelines. Seven randomized controlled trials (RCTs) (n = 8,069) were included. Pooled analyses were performed using random-effects models, including subgrouping based on type 2 diabetes status. Risk of bias was assessed with RoB 2, and certainty of evidence was graded with GRADE. CagriSema produced significantly greater weight loss than semaglutide (MD = -7.58 kg; 95% CI = -10.30 to -4.86; p < 0.00001), cagrilintide (MD -9.24 kg; 95% CI -10.46 to -8.02, p < 0.00001), and placebo (MD = -13.99 kg; 95% CI = -18.38 to -9.61; p < 0.00001). Glycemic outcomes were heterogeneous, but lipid parameters improved versus placebo. Adverse events were primarily gastrointestinal and injection-site reactions, with no increase in serious adverse events. CagriSema provides substantial and clinically meaningful weight reduction with a favorable safety profile. Importantly, it demonstrates superior efficacy to both cagrilintide and semaglutide, highlighting its therapeutic potential. Future large-scale trials are required to confirm long-term safety and durability, especially given its clear advantage over semaglutide in reducing body weight.

The amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide have complementary effects on glycaemic control and bodyweight. We aimed to investigate the efficacy and safety of a fixed-dose combination of cagrilintide and semaglutide (cagrilintide-semaglutide; known as CagriSema) versus semaglutide or cagrilintide for glycaemic control in people with type 2 diabetes and overweight or obesity.

Cagrilintide-semaglutide (CagriSema) is a novel, once-weekly combination of the amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide. We aimed to assess the efficacy and safety of cagrilintide-semaglutide for people with type 2 diabetes inadequately controlled with diet and exercise.

Basal insulin treatment for type 2 diabetes often results in inadequate glycaemic control and is associated with weight gain and increased risk of hypoglycaemia. We aimed to compare the efficacy and safety of a once per week combination of cagrilintide with semaglutide (CagriSema) versus placebo as an add-on to basal insulin in individuals with type 2 diabetes.

Fixed-dose combination of semaglutide/cagrilintide (CagriSema 2.4 mg/2.4 mg) has demonstrated significant and clinically relevant body weight reductions in adults with overweight or obesity compared with placebo.

The obesity epidemic is a major health burden that enhances susceptibility to a broad spectrum of metabolic-associated comorbidities, ranging from fatty liver disease and endocrine dysfunction to traditional risks like type 2 diabetes mellitus and cardiovascular disease. Glucagon-like peptide-1 receptor agonists, including semaglutide, facilitate weight loss alongside glucose metabolism. The dual therapy CagriSema, which combines semaglutide with cagrilintide was developed. We systematically searched MEDLINE (via PubMed), Web of Science, Scopus, and Cochrane Library, from inception to July 2025, for randomized controlled trials (RCTs) comparing CagriSema with semaglutide monotherapy or placebo in patients with obesity. Four RCTs (n = 4,419) were included (CagriSema: 3,055; control: 1,364). Pooled analysis showed that CagriSema significantly reduced percent weight loss (Cohen's d: -1.38; 95% CI: -1.84 to -0.91; I² = 94.8%). CagriSema also resulted in greater absolute weight loss (MD: -11 kg), waist circumference (MD: -9.41 cm), and systolic blood pressure (MD: -7.06 mmHg). Gastrointestinal adverse events were more frequent (RR: 1.32). CagriSema therapy was associated with superior weight reduction compared with semaglutide or placebo. In conclusion, CagriSema achieves greater weight loss than semaglutide or placebo but increases gastrointestinal adverse events, warranting careful tolerability monitoring and longer-term data.

Obesity is a complex chronic disease requiring effective long-term management. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of cagrisema and cagrilintide monotherapy compared with semaglutide in individuals with obesity.

This study evaluated the usability of the CagriSema dual-chamber pen, a single-dose, single-use, pre-filled autoinjector for once-weekly subcutaneous administration of a fixed-dose combination of cagrilintide and semaglutide. Adults with overweight/obesity (n = 85) or type 2 diabetes (n = 65) performed simulated injections after standardized training. Endpoints included injection completeness, task durations, and user feedback via the Injection Device Experience and Acceptability-Ease of Use and Convenience Questionnaire (IDEA-ECQ; content validity supported by cognitive interviews, n = 50). All but one participant completed the injection successfully. Median training time was 3 minutes, and time to prepare and inject was 15 seconds. Participants rated the device easy/very easy to use (100%), easy/very easy to learn (98.7%), and an injection with the pen convenient (99.3%). Results were consistent across populations and unaffected by prior device experience.

To assess the added value of absolute anthropometric targets alongside percentage weight loss in the clinical management of obesity.

Obesity is a global health challenge associated with substantial cardiometabolic morbidity. Cagrilintide, a long-acting amylin analogue, alone or in combination with semaglutide (CagriSema), has emerged as a novel pharmacologic strategy for weight management. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of cagrilintide-based therapies in adults with overweight or obesity.

Overweight status, obesity, and diabetes represent significant socioeconomic burdens that require long-term management.

CagriSema is a combination of amylin (cagrilintide) and glucagon-like peptide-1 (semaglutide) analogues being developed for weight management. Here, we show that CagriSema blunts metabolic adaptation in rats. Quantifying CagriSema's action on energy intake and expenditure in rats we observe 12% weight loss with a 39% reduction in food intake. By contrast, pair-feeding causes less-pronounced weight loss, while weight matching requires a 51% decrease in food intake. Therefore, approximately one-third of CagriSema's weight loss efficacy arises from an effect on energy expenditure, the blunting of metabolic adaptation, which contributes to the successful treatment of obesity.

Diabetes is a complex metabolic disorder affecting over 37 million people in the United States. Without proper management, diabetes can lead to a myriad of complications, including cardiovascular disease, kidney failure, and vision loss. Obesity is a major contributor to type 2 diabetes, but genetic and physiological factors make weight loss difficult, necessitating medication management for both conditions. Government-approved weight loss medications, including glucagon-like peptide-1 agonists and amylin analogs, have proven to be effective for both conditions. However, intensive glycemic control involving antidiabetic medications, while beneficial for reducing diabetic complications, can often precipitate hypoglycemic events, which are characterized by cardiac arrhythmias, coma, confusion, and even mortality. A new drug under investigation, CagriSema, combines cagrilintide, an amylin analog, with semaglutide, a glucagon-like peptide-1 agonist. This drug is being marketed as a safe and potentially superior medication to lower both Hemoglobin A1c and body weight. In this article, the pathophysiology, current guidelines, and management of diabetes will be reviewed, with an emphasis on the clinical evidence for tight glucose control and avoiding hypoglycemic events. Following this, an overview of recent trials on antidiabetic medications, including those involving CagriSema, will be presented, along with prospects for future trials in this promising area of research.