Cagrilintide | Benefits and Research Applications

Researchers seeking the latest insights into the potential benefits of cagrilintide, as highlighted in scientific studies, may find the following information useful.
This novel, non-selective amylin agonist peptide has recently attracted significant attention for its potential applications in weight management and metabolic disorders, including:

• Overweight and obesity
• Type 2 diabetes
• Synergistic effects with other weight loss peptides

To advance research on cagrilintide, staying informed on the most recent findings is essential.
This educational overview provides an updated collection of academic publications that outline the documented benefits of cagrilintide.
Additionally, we have listed reliable sources for acquiring cagrilintide as reference material below.

What is Cagrilintide | Overview

Cagrilintide is a synthetic peptide developed and actively studied by the Danish pharmaceutical company Novo Nordisk as a potential therapy for weight loss in obesity and glycemic control in type 2 diabetes (T2D) [1].

Here is what researchers should know about the peptide:

• Its structure is based on the 37-amino-acid hormone amylin, also known as islet amyloid polypeptide, which is endogenously secreted by the pancreas alongside insulin [1].
• The structure of cagrilintide is modified to enhance its affinity for amylin receptors (AMYRs). Consequently, cagrilintide functions as a non-selective dual agonist for amylin receptors, also activating calcitonin receptors (CTRs) [2].

• The peptide possesses a C20 fatty di-acid group, which gives cagrilintide a half-life ranging from 159 to 195 hours, allowing for once-weekly subcutaneous injections [1].

• AMYRs and CTRs are widely expressed in the brain, and when activated, suppress hunger sensations in regions such as the nucleus tractus solitarius (NTS) and area postrema (AP). This leads to reduced food consumption and energy intake, promoting weight loss [3].

• Furthermore, activating the amylin receptors slows gastric emptying and suppresses glucagon secretion, thus prolonging satiety after meals and stabilizing blood glucose levels, which is beneficial for weight management and metabolic health [4]. 

• The peptide also activates the CTRs for the thyroid hormone calcitonin, which regulates calcium homeostasis and may help lower blood glucose levels under diabetic conditions [5].

Cagrilintide is not yet approved by the U.S. Food and Drug Administration (FDA). It is currently undergoing phase 3 clinical trials in combination with semaglutide under the brand name CagriSema [1, 6]. Researchers can also obtain cagrilintide as a stand-alone peptide for laboratory experimentation only.

Research Applications and Benefits of Cagrilintide | A Comprehensive Review

The available research indicates that cagrilintide has a range of potential benefits and research applications, including significant weight loss, improved metabolic function, enhanced glycemic control, and reduced appetite. These benefits are most prominent when the peptide is introduced either alone or in combination with other classes of weight loss peptides.

Cagrilintide for Weight Management Research

Cagrilintide is primarily studied for its potential metabolic benefits alongside the weight loss peptide semaglutide. Semaglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist that has received FDA approval for the following indications:

• In T2D (type 2 diabetes), semaglutide is approved for two indications: as a treatment for glycemic control and to reduce the risk of cardiovascular events, such as heart attacks and strokes, in this population [7].
• Additionally, it is approved for managing overweight and obesity in different age groups, including adults and adolescents over 12 years old [8].

Similar to cagrilintide, semaglutide has a prolonged half-life ranging from 145 to 165 hours, which allows for once-weekly administration, either alone or in combination with cagrilintide. This combination aims to produce synergistic effects on reducing appetite and improving glycemic control, offering a comprehensive strategy for managing metabolic disorders [9, 10].

A notable phase 1b trial investigated the potential of different cagrilintide doses (up to 4.5 mg weekly) and semaglutide (2.4 mg weekly) in 96 overweight and obese individuals, compared to a control group that received placebo + semaglutide (2.4 mg weekly).

The most notable findings from this trial were [10]:

• When dosed at 2.4 mg weekly, cagrilintide + semaglutide led to an additional 7.3% weight loss compared to the placebo group (only semaglutide).
• When dosed at 4.5 mg weekly, cagrilintide + semaglutide led to an additional 7.4% weight loss compared to the placebo group (only semaglutide).
• 1.2 mg cagrilintide + semaglutide led to 15.7% weight loss; 2.4 mg cagrilintide + semaglutide led to 17.1% weight loss; 4.5 mg cagrilintide + semaglutide led to 15.4% weight loss.
• Semaglutide 2.4 mg alone typically achieves around 12.4% weight loss after 68 weeks. The combination with cagrilintide enhanced the weight loss by an additional 3.3% to 4.7%, depending on the dose of cagrilintide.
• There were 566 adverse events reported (ranging from mild to moderate), with gastrointestinal disorders being the most common (37% of events).

The results suggest that cagrilintide complements semaglutide’s GLP-1 receptor agonism by adding effects on appetite regulation, satiety, and energy intake, leading to more pronounced weight loss. Improvements in glycemic parameters were seen across all combination treatment groups, further supporting the enhanced research potential when combining these two peptides.

Cagrilintide for Weight Loss Research

Cagrilintide is still under active research for its potential weight loss effects in the REDEFINE phase 3 clinical program, initiated by Novo Nordisk.

The program is planned to include six trials investigating the effects of the peptide on individuals with overweight, obesity, type 2 diabetes (T2D), cardiovascular disease, and other conditions over 68-72 weeks.

More specifically, the trials are planned to examine the combination of cagrilintide and semaglutide (CagriSema) for weight loss in individuals with and without T2D and are currently actively recruiting subjects [11].

The program was initiated based on the positive results from phase 1 and phase 2 trials, such as the aforementioned phase 1b trial in non-diabetic individuals.

Additionally, a noteworthy phase 2 trial investigated the potential of cagrilintide alone and compared it to other GLP-1 agonists. The most notable findings from this trial were [12]:

• The study included 706 non-diabetic participants with overweight or obesity and compared cagrilintide alone to a daily dose of 3 mg of the FDA-approved GLP-1 agonist liraglutide or a placebo.
• The subjects were randomly assigned to receive weekly doses of cagrilintide (ranging from 0.3 mg to 4.5 mg) for a period of 26 weeks.
• Cagrilintide 0.3 mg weekly led to an average weight reduction of 6% (6.4 kg) compared to 3% (3.3 kg) for placebo. The estimated treatment difference was 3.0%.
• Cagrilintide 0.6 mg weekly led to an average weight reduction of 6.8% (7.1 kg), 3.8% higher than placebo.
• Cagrilintide 1.2 mg weekly led to an average weight reduction of 9.1% (9.7 kg), 6.1% higher than placebo.
• Cagrilintide 2.4 mg weekly led to an average weight reduction of 9.7% (10.3 kg), 6.7% higher than placebo.
• Cagrilintide 4.5 mg weekly led to an average weight reduction of 10.8% (11.5 kg), 7.8% higher than placebo.
• Liraglutide 3 mg daily led to a 9% weight loss, which was similar to cagrilintide 2.4 mg weekly and statistically much lower than cagrilintide 4.5 mg weekly.

The primary adverse events were gastrointestinal, with mild to moderate nausea being the most common. Obstipation was also relatively common with the amylin analog due to its effects on slowing gastric emptying.

All of these side effects were successfully resolved. The overall discontinuation rate due to side effects was around 10% [12].

Cagrilintide in Type 2 Diabetes Research

Cagrilintide, in combination with semaglutide (CagriSema), is also under active research as a potential therapy for T2D as part of the REIMAGINE phase 3 clinical program.

As of 2024, Novo Nordisk has initiated three out of four pre-planned trials that are actively recruiting subjects and should last 40-68 weeks. The first results are expected as soon as 2025-2026 [13, 14, 15].

This program is based on the successful results from phase 2 trials with cagrilintide + semaglutide in T2D patients with overweight or obesity.

More specifically, the combination of cagrilintide and semaglutide proved superior to either peptide alone for improving glycemic control and reducing excess body weight in T2D patients.

Participants were randomly assigned in a 1:1:1 ratio to receive cagrilintide + semaglutide (2.4 mg weekly each), 2.4 mg weekly semaglutide alone, or 2.4 mg weekly cagrilintide alone.
The trial yielded the following results [16]:

• CagriSema led to the greatest decrease in fasting glucose (–3.3 mmol/L), compared to cagrilintide (–1.7 mmol/L) and semaglutide (–2.5 mmol/L) alone.
• From baseline to week 32, CagriSema resulted in a significant reduction in glycated hemoglobin (a marker of long-term glycemic control) by –2.2%, whereas cagrilintide alone achieved a –0.9% reduction, and semaglutide alone led to a –1.8% reduction.
• The highest reduction in body weight was observed in the CagriSema group (–15.6%), followed by the cagrilintide (–8.1%) and semaglutide (–5.1%) groups.

It appears that cagrilintide can greatly improve the weight loss and anti-diabetic effects of the GLP-1 agonist semaglutide.

Moreover, 2.4 mg weekly cagrilintide on its own proved more effective for weight loss than an equivalent dose of semaglutide. When the two are applied simultaneously, they appear to exert a synergistic weight loss effect, achieving even greater weight loss.

Recommended Dosage for Cagrilintide

Based on available scientific publications, cagrilintide is administered once weekly due to its extended half-life. It must be initiated at a relatively low weekly dose, which is then gradually increased to a maintenance dose [10].

The published phase 1 and phase 2 trials have achieved a dosage of up to 4.5 mg/week by initiating therapy at 0.3 mg/week and gradually increasing the dose every four weeks for a total of 17 weeks [12]. This gradual increase helps reduce the risk of side effects, such as gastrointestinal issues.

The dosing protocols used in the ongoing phase 3 trials of cagrilintide in combination with semaglutide involve even more gradual dosing schemes, starting at 0.25 mg/week and reaching a maximum dosage of 2.4 mg/week within 17 weeks [17].

The following dosing protocol is based on the currently ongoing phase 3 trials and serves as a guideline for assessing cagrilintide's efficacy in weight management for obese participants:

• Cagrilintide Weekly Dose: Published trials have started cagrilintide at 0.25 mg/week for the first four weeks, followed by 0.5 mg/week during weeks 5-8, 1 mg/week during weeks 9-12, 1.7 mg/week during weeks 13-16, and 2.4 mg/week from week 17 onward. Depending on desired outcomes and patient response, doses may be maintained at 2.4 mg/week or escalated to a maintenance dose of 4.5 mg/week starting from week 21.
• Study Duration: Published studies have lasted up to 32 weeks at 2.4 mg/week and up to 26 weeks at 4.5 mg/week. Phase 3 trials are planned to last 40-72 weeks at a dose of 2.4 mg/week.
• Notes: The maximum weekly dose should not exceed 4.5 mg.

Where to Buy Cagrilintide Online? | 2024 Edition

For researchers, obtaining high-purity peptides is critical to ensuring the accuracy and reliability of experimental outcomes. With many suppliers offering research peptides, identifying a dependable source for Cagrilintide can be challenging.

After evaluating several vendors, our review team found Arctic Peptides to consistently deliver top-quality options to buy Cagrilintide, meeting the most rigorous scientific standards for purity and reliability.

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