Cagrilintide Dosage Guideline

Researchers may find it difficult to determine the optimal cagrilintide dosage for their studies due to the limited and varied data currently available.

This novel peptide is still undergoing phase 3 trials and early data suggests significant potential for various research applications. In particular, recent studies indicate its effectiveness at therapeutic doses for:

• Chronic weight management in cases of overweight and obesity.
• Improving glycemic control in type 2 diabetes (T2D).
• Potentially reducing cardiovascular events in at-risk populations.

To maximize the research potential of cagrilintide, it is crucial for scientists to stay informed about the latest evidence regarding dosing and safety protocols.

This overview aims to provide researchers with a cagrilintide dosage calculator based on the most recent clinical trials, as well as guidance on sourcing research-grade cagrilintide, ensuring studies adhere to the highest scientific standards.

What is Cagrilintide | Overview

Cagrilintide, also known as AM833, is a synthetic peptide developed by Novo Nordisk as a potential treatment for weight loss and T2D.

This peptide is derived from amylin, a 37-amino-acid hormone naturally secreted by the pancreas alongside insulin. Amylin helps reduce glucagon levels post-meal, slows gastric emptying, and promotes satiety [1].

Cagrilintide functions as a dual amylin and calcitonin receptor agonist (DACRA) by targeting receptors responsive to both amylin and calcitonin. Here are more details:

• Calcitonin, a hormone produced by the thyroid gland, plays a role in calcium homeostasis by facilitating calcium deposition in bones. Research indicates activating its receptors by peptides like cagrilintide, may also contribute to lowering blood glucose levels in T2D [2].
• Cagrilintide activates the amylin receptors in the appetite-controlling regions of the brain, particularly the nucleus tractus solitarius (NTS) and area postrema (AP), potentially reducing the desire for food intake and promoting weight loss [3].
• Activating these receptors also slows gastric emptying and inhibits glucagon secretion, which can extend the feeling of fullness after meals and stabilize blood glucose levels, supporting weight management and overall metabolic health [4].
• The peptide's effectiveness is enhanced by several amino acid substitutions and the addition of a C-20 fatty di-acid via an α-glutamyl spacer, extending its half-life to approximately 7.3 days, enabling once-weekly subcutaneous injections [5].

Cagrilintide is currently under investigation in phase 3 clinical trials (REDEFINE and REIMAGINE) in combination with semaglutide, marketed as CagriSema [5, 6].

Semaglutide, another peptide developed by Novo Nordisk, is already FDA-approved for glycemic control, reducing cardiovascular event risks in T2D, and managing obesity in individuals aged 12 and older [7, 8].

It mimics the incretin hormone GLP-1, stimulating insulin release and suppressing appetite, with a half-life exceeding one week.

The GLP-1 receptors are expressed by a different population of appetite-suppressing nerve cells in the brain, so the combination of cagrilintide + semaglutide may enhance appetite suppression [9].

Cagrilintide has not yet received approval from the U.S. Food and Drug Administration (FDA), but the trials of cagrilintide + semaglutide are ongoing. Cagrilintide is only available for research purposes to qualified professionals.

Cagrilintide Dosage Chart | Quick Breakdown

Timeline	Weeks 1-4	Weeks 5-8	Weeks 9-12	Weeks 13-16	Weeks 17+ (full dose)
Cagrilintide Weight Loss Dose for Research [1x weekly]	0.25mg	0.5mg	1mg	1.7mg	2.4mg

 

Recommended Dosage for Cagrilintide Research

Based on comprehensive clinical trial data, cagrilintide has shown significant benefits when administered correctly in research studies.

Notably, the peptide has been dosed in research areas such as weight management, blood sugar control, and effects on cardiovascular health.

Below we break down the most notable dosing regimes used in phase 1, phase 2, and phase 3 clinical trials.

Cagrilintide Dosage for Weight Management Research

Cagrilintide is under active investigation for its weight loss potential in individuals without T2D.

In the available phase 1b and phase 2 weight loss trials, researchers have dosed cagrilintide with and without semaglutide.

For example, a 20-week phase 1b trial in overweight and obese participants involved six different dosages of cagrilintide (0.16, 0.3, 0.6, 1.2, 2.4, and 4.5mg/weekly) alongside 2.4mg/weekly semaglutide, and a control group receiving 2.4mg/weekly semaglutide only.

Here is what researchers should know [10]:

• Each of the treatment groups was initiated at about ten times lower dosage, which is then incrementally increased every 4 weeks for 16 weeks.
• The 1.2, 2.4, and 4.5mg/weekly cagrilintide + semaglutide groups were more effective than semaglutide alone.
• Interestingly, the 2.4mg/weekly cagrilintide + semaglutide led to the highest weight loss from baseline (-17.1%), while both the 2.4 and 4.5mg/weekly cagrilintide + semaglutide led to an identical placebo-adjusted weight loss of -7.4%

A larger phase 2 trial in 706 overweight and obese individuals used a different dosing protocol for cagrilintide and the peptide was administered without the addition of semaglutide. Instead, the peptide was compared to the FDA-approved daily GLP-1 agonist liraglutide.

Here is what researchers should know about the dosage in this trial [11]:

• Two of the therapy groups were initiated and remained on 0.3mg/weekly and 0.6mg/weekly for the whole 26 weeks of the trial
• In three other groups, the dosage was escalated every 2 weeks until achieving 1.2, 2.4, and 4.5mg/weekly cagrilintide.
• 1.2mg and 2.4mg/weekly cagrilintide had similar effectiveness to daily liraglutide, while 4.5mg/weekly semaglutide was significantly more effective for weight loss.

The phase 3 trials on cagrilintide for weight loss in people without T2D are currently ongoing and involve dosing similar to that for semaglutide which includes initiating at 0.25mg/weekly and gradual titration every 4 weeks for 16 weeks, until a maximum of 2.4mg/weekly.

Cagrilintide Dosage for Diabetes Research

Researchers have investigated cagrilintide for managing blood sugar levels in patients with T2D only when combined with semaglutide.
In a 32-week phase 2 trial, researchers evaluated the efficacy of a cagrilintide + semaglutide combination vs either peptide alone in 92 patients with T2D. Here is what researchers should know about the dosing and findings in this trial [12]:

• The three treatment groups (cagrilintide + semaglutide, semaglutide alone, or cagrilintide alone) received doses that were escalated every 4 weeks from 0.25mg to 0.5mg, 1.0mg, and 1.7mg until the maintenance dose of 2.4mg/weekly was reached after 16 weeks.
• The 2.4mg/weekly dose was then maintained for another 16 weeks. Weight reduction was highest in the 2.4mg/weekly cagrilintide + 2.4mg/weekly semaglutide combo group (-15.6% from baseline), followed by cagrilintide alone (-8.1%) and semaglutide alone (-5.1%).
• On the other hand, fasting glucose levels fell most significantly with the cagrilintide + semaglutide combo (-3.3mmol/L), compared to semaglutide alone (-2.5mmol/L) and cagrilintide alone (-1.7mmol/L).

The phase 3 clinical program REIMAGINE which also targets T2D patients has four ongoing trials (REIMAGINE 1-4), and all trials use the same 16-week dosing protocol with a maximum dosage of 2.4mg/weekly cagrilintide + 2.4mg/weekly semaglutide [13, 14].

The largest of these trials is REIMAGINE 2 which is planned to last 68 weeks (16 weeks dose escalation and 52 weeks maintenance) and include 2,700 T2D patients on metformin (MET) with or without SGLT-2 inhibitors.

The trial will compare cagrilintide + semaglutide against semaglutide, cagrilintide, and placebo, with both glycated hemoglobin (HbA1c – a marker of long-term T2D control) and body weight as primary outcomes [15].

Cagrilintide Dosage for Other Research Objectives

REDEFINE is a phase 3 clinical program by Novo Nordisk to investigate the weight loss potential of cagrilintide + semaglutide in different populations [16].

Currently, cagrilintide is being tested for its effects on cardiovascular health and the risks of major adverse cardiovascular events (MACE) in one of the six trials from the REDEFINE phase 3 clinical program.

The trial (REDEFINE-3) is planned to include 7000 participants with or without T2D who are overweight or obese.

As of 2024, the trial is still in the recruiting phase, but it is planned to involve a cagrilintide + semaglutide dosing protocol similar to those in the other phase 3 trials from the REDEFINE and REIMAGINE clinical programs.

This involved escalation every 4 weeks from 0.25mg to 0.5mg, 1.0mg, and 1.7mg until the maintenance dose of 2.4mg/weekly is reached after 16 weeks. The study will last for up to 4.5 years [17].

Cagrilintide Dosage Calculator

Cagrilintide is generally administered once a week due to its long half-life, with a maximum dose of 4.5mg/weekly when used alone, or 2.4mg/weekly when combined with semaglutide [10, 11].

In current phase 3 trials, cagrilintide is being dosed alongside semaglutide, starting at 0.25mg/weekly and gradually increasing to a maximum of 2.4mg/weekly by the 17th week, following a 16-week dose escalation period [16].

If researchers consider it appropriate, a possible dosage increase to 4.5mg/weekly may occur only after week 21.

The following dosing schedule outlines the protocol for evaluating cagrilintide's effectiveness in weight management for obese participants in ongoing phase 3 trials:

• Weekly Dose Progression: The initial dose in published research is 0.25mg/weekly for the first four weeks, followed by 0.5mg/weekly during weeks 5-8. The dose increases to 1mg/weekly for weeks 9-12, then to 1.7mg/weekly for weeks 13-16, and reaches a maintenance dose of 2.4mg/weekly starting from week 17.
• Administration Frequency: The injection is administered once a week via subcutaneous injection, usually in the abdominal area.
• Study Duration: Published studies have lasted up to 32 weeks with a dose of 2.4mg/weekly and up to 26 weeks at 4.5mg/weekly. Ongoing trials are expected to last up to 4.5 years with a 2.4mg/weekly dose.
• Note: The maximum weekly dose should not exceed 4.5mg, and researchers must rotate injection sites to reduce the risk of local side effects.

Cagrilintide Benefits | Overview

The ongoing phase 3 trials from the REDEFINE and REIMAGINE clinical programs are expected to provide the most comprehensive data on the potential benefits of cagrilintide + semaglutide for weight loss and T2D management.

The expected completion date for the different trials varies between 2025 and 2027. Until then, researchers can get familiar with the most notable benefits as outlined by phase 1b and phase 2 trials:

• Appetite suppression and weight loss: The 26-week phase 2 trial in 706 overweight and obese participants without T2D reported -9.7% (-22.7lb) weight loss from baseline with 2.4mg/weekly and -10.8% (-25.4lb) with 4.5mg/weekly cagrilintide. In comparison 3mg/daily liraglutide led to -9% of weight loss from baseline [11].
• Synergistic weight loss potential with GLP-1 agonists: The 20-week phase 1b trial in 96 overweight and obese participants without T2D reported -17.1% mean reduction of baseline weight with 2.4mg/weekly cagrilintide + semaglutide. Both the 2.4mg/weekly and 4.5mg/weekly cagrilintide + semaglutide groups led to an additional -7.4% weight loss versus the semaglutide-only group [10].
• Blood sugar control and weight loss in T2D: The 32-week phase 2 study in 92 participants with T2D revealed that 2.4mg/weekly cagrilintide + semaglutide led to a reduction from baseline levels of HbA1c by -2.2%, fasting blood sugar by –3.3 mmol/L and body weight by -15.6% [12].

All trials reported greater improvements with cagrilintide + semaglutide versus either of the peptides alone. Further, 2.4mg/weekly cagrilintide appeared to have greater weight loss potential but weaker anti-diabetic action compared to 2.4mg/weekly semaglutide.

Cagrilintide Side Effects | Overview

Most side effects observed in cagrilintide trials are dose-dependent, primarily involving gastrointestinal issues.

These side effects are generally temporary and can be managed by gradually increasing the weekly dosage. Lifestyle changes like drinking more water, increasing fiber intake, and staying physically active can also help alleviate side effects such as constipation.

In the largest study to date, a phase 2 trial with 706 overweight or obese participants, side effects were common across all doses, ranging from 0.3 to 4.5mg/week [11].

At the highest dose, 88% of participants reported side effects, with 63% experiencing gastrointestinal problems. Only one participant in the 4.5mg/week group withdrew due to side effects.

Among the 101 participants receiving the highest dose of 4.5mg/week, the most frequently reported side effects were:

• Nausea: 47%
• Injection site reactions: 43%
• Fatigue: 20%
• Constipation: 21%
• Allergic reactions: 10%
• Vomiting: 8%
• Headache: 7%
• Loose stools: 7%
• Indigestion: 4%

The incidence of serious side effects in this phase 2 trial ranged from 2% to 7% in the cagrilintide groups, compared to 4% in the liraglutide group and 3% in the placebo group.

One participant receiving 4.5mg/week of the peptide experienced acute cholelithiasis (gallstones), which may be related to cagrilintide.

All reported side effects were successfully resolved. The overall discontinuation rate due to side effects across all doses was approximately 10% [11].

Safety Considerations and Contraindications

As of 2024, cagrilintide has not been approved for human use and is currently being evaluated in a phase 3 clinical trial in combination with semaglutide.

Previous phase 1 and phase 2 trials have demonstrated that cagrilintide is well-tolerated, with a safety profile similar to FDA-approved GLP-1 agonists like semaglutide and liraglutide, and FDA-approved amylin analogs such as pramlintide [1].

Cagrilintide also led to the production of anti-cagrilintide antibodies, with their incidence increasing with both dosage and exposure duration, affecting 46–73% of participants by week 26.

However, these antibodies did not appear to influence changes in body weight, and no serious allergic reactions were reported [11].

The ongoing phase 3 trials, part of the REIMAGINE and REDEFINE clinical programs, are expected to provide more detailed information on the safety and potential adverse effects of this peptide when used alongside semaglutide.

Where to Buy Cagrilintide Online | 2024 Edition

Maintaining the accuracy and consistency of experimental data heavily depends on sourcing peptides with high purity. However, the challenge lies in finding a reliable supplier for Cagrilintide amidst a crowded market.

After an in-depth review of several vendors, our team found that Arctic Peptides consistently delivers Cagrilintide of superior quality, aligning with the most stringent scientific standards for purity and dependability.

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