Cagrilintide for Weight Loss | How Does It Work

Researchers interested in investigating the potential of cagrilintide for weight loss can use this guide to gain insights into this promising peptide.

Although cagrilintide has not yet been approved for human use by regulatory authorities, clinical trials are currently exploring its effectiveness in combination with other peptides regarding several key areas:

• Weight reduction in individuals with overweight and obesity
• Weight management in diabetes
• Glycemic control

Based on the latest research and peer-reviewed studies, we will highlight the documented benefits of cagrilintide for weight management, along with important considerations regarding side effects and dosage.

Finally, this guide offers expert advice on purchasing high-quality cagrilintide online, allowing qualified researchers to incorporate this peptide into their studies safely and effectively.

What is Cagrilintide | Overview

Cagrilintide (aka AM833) is a synthetic peptide developed by the Danish pharmaceutical company Novo Nordisk.

It belongs to a class of drugs known as DACRAs, or Dual Amylin and Calcitonin Receptor Agonists. This class of drugs targets receptors in the brain that are naturally activated by the hormones amylin and calcitonin.

These peptide hormones play important roles in regulating appetite, glucose metabolism, and body weight:

• Amylin is a 37 amino acid peptide hormone secreted by the pancreas that helps control blood sugar levels by slowing gastric emptying and promoting satiety [1].
• Calcitonin, produced by the thyroid gland, is primarily involved in calcium homeostasis but also influences energy balance and metabolism [2].

Cagrilintide was developed to enhance these effects by combining the actions of amylin and calcitonin receptor activation, thereby offering a novel approach to weight management and metabolic disorders.

The peptide’s structure consists of 37 amino acids, based on the structure of amylin.

Novo Nordisk employed various strategies, including chemical modification of the peptide chain and the addition of fatty acid side chains, to slow its degradation and prolong its action in the body.

Consequently, the peptide has a half-life of 7.3 days, which allows for once-weekly subcutaneous injections and more consistent therapeutic effectiveness [3].

Cagrilintide is currently under investigation in combination with semaglutide, another innovative drug developed by Novo Nordisk that [4, 5]:

• Mimics another natural hormone called glucagon-like peptide-1 (GLP-1)
• Has shown substantial effectiveness in promoting weight loss and improving glycemic control in people with type 2 diabetes (T2D)
• Has been approved by the U.S. Food and Drug Administration (FDA) for weight loss in adolescents and adults, as well as in the management of T2D

On the other hand, cagrilintide is not yet approved by the FDA, but the ongoing phase 3 trials are expected to highlight its safety, effectiveness, and synergism with semaglutide in their glucose-lowering and appetite-suppressing properties [6, 7].

Cagrilintide is also available as a reference material for laboratory research.

Cagrilintide Side Effects | Overview

While cagrilintide is still in phase 3 trials regarding its safety and effectiveness, several smaller human trials have already been completed and published.

The phase 1 and phase 2 studies indicate that cagrilintide is generally well-tolerated, with a safety profile comparable to other FDA-approved amylin analogs, such as pramlintide, which is approved for managing satiety and glucagon levels in both type 1 and type 2 diabetes [1].

Common side effects associated with amylin agonists like cagrilintide include gastrointestinal issues and delayed gastric emptying, resulting in symptoms such as nausea and constipation. These side effects can be mitigated by gradually increasing the dosage and maintaining adequate hydration.

The most extensive study conducted so far is a phase 2 trial involving 706 participants who received a maximum dose of 4.5 mg weekly. It is noteworthy that this dosage is nearly double the 2.4 mg weekly dose currently being tested in phase 3 trials [8].

Despite the higher dose, cagrilintide was well-tolerated among the 101 participants who received 4.5 mg weekly, leading to the following side effects:

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

At this highest dosage, 88% of participants reported side effects, with 63% experiencing gastrointestinal issues. However, only one participant discontinued due to side effects.

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

One potentially cagrilintide-related serious side effect was acute cholelithiasis (gallbladder stones) in a participant receiving 4.5 mg weekly.

All mild, moderate, or serious side effects potentially associated with the peptide were successfully resolved. The overall discontinuation rate due to side effects was approximately 10% [8].

The ongoing phase 3 clinical program aims to provide more comprehensive data on the efficacy and safety of cagrilintide, particularly in combination with semaglutide, a GLP-1 agonist with a similar safety profile and side effect spectrum.

How Cagrilintide Works for Weight Loss

DACRAs like cagrilintide function by activating both the amylin and calcitonin receptors, which are G-protein-coupled receptors (GPCRs) essential for appetite regulation, weight management, and overall metabolic health.

The following are key mechanisms that may account for the significant weight loss associated with cagrilintide use [9, 10]:

• Amylin receptors are predominantly located in brain regions involved in appetite control, such as the nucleus tractus solitarius (NTS) and area postrema (AP). These receptors are formed when the calcitonin receptor (CTR) pairs with receptor activity-modifying proteins (RAMPs).
• The activation of amylin receptors seems to influence different neuron populations in the area postrema compared to other weight-loss peptides, such as GLP-1 agonists. This could explain the enhanced effects observed when DACRAs are used in combination with GLP-1 agonists.
• Calcitonin receptors also play a role in metabolic regulation, although their exact functions are not fully understood. By targeting both amylin and calcitonin receptors, cagrilintide may offer a more robust and sustained reduction in food intake compared to amylin analogs alone.
• Additionally, DACRAs like cagrilintide may influence the brain’s reward pathways, particularly in the ventral tegmental area (VTA) and nucleus accumbens (NAc), which are linked to the motivation to consume high-calorie, palatable foods.
• Cagrilintide also slows gastric emptying, prolonging the sensation of fullness after eating and reducing the desire to snack between meals.
• Leptin, a hormone that signals the brain to curb appetite and boost energy expenditure, may have enhanced signaling due to cagrilintide, potentially alleviating some level of leptin resistance commonly seen in obesity.

Benefits of Cagrilintide for Weight Loss

All published clinical trials showcase a significant weight loss during cagrilintide experimentation, to an extent where the peptide matches or even outperforms FDA-approved weight loss peptides like GLP-1 agonists.

Below, we have outlined the most important clinical trials that researchers should be aware of.

Cagrilintide for Weight Loss in T2D

Type 2 diabetes (T2D) is frequently associated with excess body fat, especially around the abdomen. To explore new treatment possibilities, researchers conducted a 32-week phase 2 trial assessing the effects of cagrilintide and the well-known anti-diabetic and weight loss peptide, semaglutide.

Participants were randomly assigned to one of three groups: one receiving 2.4 mg of semaglutide weekly, another receiving 2.4 mg of cagrilintide weekly, and a third group receiving both treatments combined (cagrilintide + semaglutide).

The findings were as follows [11]:

• When administered alone, 2.4 mg/week of cagrilintide led to an 8.1% reduction in baseline body weight, surpassing the 5.1% reduction observed with 2.4 mg/week of semaglutide. The combination of both drugs produced an even greater effect, resulting in a 15.6% reduction in body weight.
• Regarding glycemic control, semaglutide proved more effective than cagrilintide, lowering glycated hemoglobin (HbA1c) levels by 1.8% compared to cagrilintide’s 0.9% reduction. Additionally, semaglutide decreased mean fasting glucose levels by 2.5 mmol/L, while cagrilintide lowered them by 1.7 mmol/L.

Interestingly, cagrilintide also appeared to boost semaglutide's glycemic control when used together, achieving reductions of 2.2% in HbA1c and 3.3 mmol/L in fasting blood sugar levels.

Cagrilintide for Weight Management in Non-Diabetics

The research on cagrilintide's potential weight loss effects in individuals with obesity but without type 2 diabetes (T2D) includes two important clinical trials: a phase 1b trial and a phase 2 trial.

The phase 1b trial, conducted over 20 weeks, involved 96 adults aged 18-55 with overweight or obesity. Participants were divided into six cohorts, each receiving different weekly doses of cagrilintide (ranging from 0.16 to 4.5 mg) in combination with 2.4 mg semaglutide.

Control groups were given semaglutide along with placebo injections. The results were as follows [12]:

• The group receiving 2.4 mg/week cagrilintide plus semaglutide experienced a 17.1% weight reduction, compared to a 9.8% reduction in the placebo plus semaglutide group (a difference of 7.3%).
• The group receiving 4.5 mg/week cagrilintide plus semaglutide saw a 15.4% weight reduction, compared to 8% in the placebo group (a difference of 7.4%).

The phase 2 trial involved 706 participants with overweight or obesity but without T2D. They were randomly assigned to receive weekly doses of cagrilintide (ranging from 0.3 mg to 4.5 mg), a daily dose of the GLP-1 agonist liraglutide (3 mg), or a placebo.

Over 26 weeks, cagrilintide produced dose-dependent weight loss, with reductions reaching nearly 11% from baseline. Specifically [8]:

• The lowest dose of 0.3 mg/weekly cagrilintide resulted in a 6% (14.1lb) mean weight loss, while the highest dose of 4.5 mg/week led to a 10.8% (25.4lb) reduction.
• All cagrilintide doses were significantly more effective than the 3% (7.3lb) mean weight loss with placebo.
• The 4.5 mg/week dose was notably more effective than the 9% mean weight loss achieved with liraglutide, while the 2.4 mg/week cagrilintide dose resulted in weight loss comparable to that of liraglutide.

Future Cagrilintide Weight Loss Research

Novo Nordisk has launched two phase 3 clinical programs to further explore the potential of cagrilintide, particularly in combination with semaglutide.

These programs consist of multiple clinical trials. The first program, named REIMAGINE, focuses on evaluating the efficacy of the peptide combination in managing type 2 diabetes (T2D). This program includes four trials, each lasting between 40 to 68 weeks. Three of these trials are currently recruiting participants, with initial results anticipated between 2025 and 2026 [13, 14, 15].

In addition to its effects on T2D, Novo Nordisk is also investigating the weight loss potential of cagrilintide through the REDEFINE program, which involves participants with and without T2D. This program comprises six trials, five of which have been outlined [16]:

• REDEFINE 1: A 68-week trial involving 3,400 participants, comparing the weight loss effects of cagrilintide combined with semaglutide against each peptide individually or placebo.
• REDEFINE 2: A 68-week trial with 1,200 participants, comparing cagrilintide plus semaglutide against placebo for weight loss.
• REDEFINE 3: A large-scale trial involving 7,000 participants, focusing on the impact of cagrilintide plus semaglutide on major adverse cardiovascular events over a period of up to 4.5 years.
• REDEFINE 4: A 72-week trial with 800 participants, comparing weight loss outcomes of cagrilintide plus semaglutide against tirzepatide.
• REDEFINE 6: A 68-week trial involving 300 participants in East Asia, comparing weight loss results of cagrilintide plus semaglutide against semaglutide 2.4 mg/weekly.

These studies are all recruiting patients as of 2024 and will be critical to understanding the weight loss benefits and safety profile of cagrilintide, both alone and in combination with semaglutide.

Cagrilintide Dosage for Weight Loss

Cagrilintide has been administered in various ways in phase 1 and phase 2 studies, depending on whether it was given alone or in combination with semaglutide.

For instance, in one phase 2 trial where cagrilintide was used without semaglutide, doses were escalated up to 4.5 mg per week over 17 weeks [8].

Conversely, in studies where cagrilintide was combined with semaglutide, including phase 2 and ongoing phase 3 trials, the dose of cagrilintide was titrated to a maximum of 2.4 mg per week within the same 17-week period [11].

Regardless of the dosing strategy, cagrilintide is administered once a week due to its prolonged half-life. It is always initiated at a lower dose as a precaution to minimize side effects and associated risks [12].

The dosing regimen in the ongoing phase 3 trials involving cagrilintide combined with semaglutide starts at 0.25 mg per week, gradually increasing to a maximum of 2.4 mg per week over 17 weeks [16].

The following dosing protocol, based on the current phase 3 trials, is intended to evaluate cagrilintide's effectiveness in managing weight in obese participants:

• Cagrilintide Weekly Dose: Trials have started with 0.25 mg per week for the first four weeks, increasing to 0.5 mg per week during weeks 5-8, 1 mg per week during weeks 9-12, 1.7 mg per week during weeks 13-16, and reaching 2.4 mg per week from week 17 onward. Depending on the patient’s response and desired outcomes, the dose may be maintained at 2.4 mg per week or increased to 4.5 mg per week starting from week 21.
• Study Duration: Published studies have maintained a dose of 2.4 mg per week for up to 32 weeks and 4.5 mg per week for up to 26 weeks. The ongoing phase 3 trials are designed to last 40-72 weeks at a 2.4 mg per week dose.
• Notes: The maximum weekly dose should not exceed 4.5 mg.

Where to Buy Cagrilintide Online? | 2024 Edition

Buying high-purity peptides is essential to achieving accurate and reliable experimental results. With a wide range of suppliers offering research peptides, selecting a reliable source for Cagrilintide can be a daunting task.

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