Cagrilintide | A Comprehensive Peptide Overview

Researchers may be looking for a comprehensive overview of cagrilintide – a novel peptide that activates the amylin and calcitonin receptors, to suppress appetite, slow down postprandial gastric emptying, and inhibit glucagon secretion outside of hypoglycemic states.

This research chemical is studied for a wide range of applications, including:

• Weight Loss Research
• Type 2 Diabetes Research
• Metabolic Improvement

To fully harness the research potential of cagrilintide, it is essential for researchers to remain informed about the latest developments. 

This in-depth guide is designed to equip scientists with critical insights into the study and experimentation of cagrilintide. 

Furthermore, we provide guidance on sourcing high-quality, research-grade cagrilintide, ensuring that studies maintain the highest levels of scientific rigor and accuracy.

What is Cagrilintide

Cagrilintide (aka AM833, NNC0174-0833, and GLXC-26801) is a synthetic peptide that acts as a dual amylin and calcitonin receptor agonist (DACRA) based on human amylin. Researchers unfamiliar with these hormones should know that:

• Amylin, also known as islet amyloid polypeptide, is a 37-amino-acid peptide hormone secreted by the pancreas alongside insulin. It reduces glucagon levels after meals, slows gastric emptying, and increases satiety [1].
• Calcitonin is another naturally occurring hormone produced by the thyroid gland. It regulates calcium homeostasis by promoting calcium accumulation within the bones. Research also suggests that it may help lower blood glucose levels under diabetic conditions [2].

Below is more detailed information for researchers about cagrilintide [3]:

• Cagrilintide, developed by Novo Nordisk, is designed to mimic the natural effects of amylin on the amylin and calcitonin receptors to regulate blood sugar, digestive motility, and, most importantly, appetite.
• The peptide achieves enhanced receptor activity compared to naturally occurring amylin by incorporating specific amino acid substitutions.
• The peptide also features the attachment of a C-20 fatty diacid via an α-glutamyl spacer, prolonging its half-life to up to 7.3 days, which allows for once-weekly subcutaneous injections.
• The primary research focus of cagrilintide studies is on weight management and the treatment of obesity and obesity-related conditions, such as type 2 diabetes (T2D).

While not yet approved by the U.S. Food and Drug Administration (FDA), it is currently being actively investigated in phase 3 clinical trials in combination with semaglutide under the trade name CagriSema [3, 4].

Semaglutide is a peptide already approved by the FDA as a standalone once-weekly injection for glycemic control and cardiovascular event risk reduction in T2D. It is also approved for managing overweight and obesity in children older than 12 and adults [5, 6].

Semaglutide also has an extended half-life lasting over one week and works by mimicking the function of the incretin hormone glucagon-like peptide-1 (GLP-1), which stimulates insulin release and suppresses appetite.

Combining cagrilintide and semaglutide appears to create synergistic effects on reducing appetite and improving glycemic control, providing a comprehensive strategy for managing metabolic disorders [7].

Cagrilintide is also available for laboratory research by qualified professionals.

Cagrilintide | Breakthrough in Obesity Research

Cagrilintide functions as a non-selective agonist for amylin receptors (AMYRs) and calcitonin receptors (CTRs). It is designed to help manage obesity through mechanisms that reduce food intake and promote weight loss in a dose-dependent manner [1].

Below are the specific mechanisms behind this weight loss effect: 

• The primary mechanism of cagrilintide involves its interaction with AMYRs and CTRs, which are widely expressed in the brain and are crucial for regulating satiety.
• By activating these receptors, cagrilintide effectively communicates a sense of fullness to the brain's homeostatic centers, particularly in the nucleus tractus solitarius (NTS) and area postrema (AP) of the brainstem. This may reduce patients' desire to eat and decrease their overall food intake, leading to weight loss [8].
• Cagrilintide slows gastric emptying and suppresses glucagon secretion. These effects contribute to longer periods of satiety after meals and more stable blood glucose levels, which are beneficial for weight management and metabolic health.

However, the effects on gastric emptying and glucagon occur only postprandially when blood sugar levels are elevated, meaning that amylin analogs like cagrilintide do not impede the production of glucagon or normal gastric emptying during normal blood sugar levels [9].

As a result, the peptide can help lower blood sugar but does not pose a risk of hypoglycemia. 

Cagrilintide | Range of Research Applications

Cagrilintide was developed in the early 2010s by the Danish pharmaceutical company Novo Nordisk, with the primary aim to target metabolic conditions like obesity and T2D.

Below we have outlined some of the most notable research applications of cagrilintide, based on the available clinical trials.

Cagrilintide for Weight Management Research

Research regarding the potential weight loss effects of cagrilintide in people with obesity (but without T2D) includes notable phase 1b and phase 2 clinical trials, while phase 3 trials are currently underway.

The phase 1b trial involved 96 non-diabetic adults aged 18-55 with overweight or obesity and lasted for 20 weeks.

The study included six sequential, overlapping cohorts receiving varying weekly doses of cagrilintide (0.16 to 4.5 mg), combined with 2.4 mg semaglutide. Control groups received only semaglutide as an active comparator alongside placebo injections.

The researchers reported the following findings [10]:

• The 2.4 mg/weekly cagrilintide + semaglutide group experienced a -17.1% weight reduction compared to -9.8% in the matched placebo plus semaglutide group (a difference of -7.3%).
• The 4.5 mg/weekly cagrilintide + semaglutide group achieved a -15.4% weight reduction versus -8% in the matched placebo group (a difference of -7.4%).

The phase 2 trial involved 706 non-diabetic participants with overweight or obesity. Participants were randomized to receive various weekly doses of cagrilintide (0.3 mg to 4.5 mg/weekly), a daily dose of another FDA-approved GLP-1 agonist with a shorter half-life called liraglutide (3 mg/daily), or a placebo.

Cagrilintide led to dose-dependent weight loss over 26 weeks, with reductions ranging from -6% to -10.8%, compared to -3% with placebo and -9% with liraglutide [11].

Cagrilintide for Research into Glycaemic Control 

Researchers have investigated cagrilintide for managing blood sugar levels in patients with T2D (type 2 diabetes) when combined with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide.

In a 32-week phase 2 trial, researchers evaluated the efficacy of a cagrilintide and semaglutide combination (marketed as CagriSema) for overweight and obese T2D patients.

The scientists divided the subjects into three equal groups, each receiving either 2.4 mg/weekly semaglutide, 2.4 mg/weekly cagrilintide, or both doses combined (cagrilintide + semaglutide combo). The results were as follows [12]:

• Weight reduction was highest in the cagrilintide + semaglutide combo group (-15.6%), followed by cagrilintide alone (-8.1%) and semaglutide alone (-5.1%).
• HbA1c levels significantly decreased by -2.2% with the cagrilintide + semaglutide combo, -1.8% with semaglutide alone, and -0.9% with cagrilintide alone.
• Fasting glucose levels fell most significantly with the cagrilintide + semaglutide combo (-3.3 mmol/L), compared to semaglutide alone (-2.5 mmol/L) and cagrilintide alone (-1.7 mmol/L).

As evident from the results, 2.4 mg/weekly cagrilintide proved more effective for weight reduction than 2.4 mg/weekly semaglutide. Moreover, cagrilintide significantly enhances the weight loss and antidiabetic properties of the GLP-1 agonist semaglutide.

Cagrilintide’s Ongoing Research into T2D and Obesity

Novo Nordisk has initiated the ambitious REDEFINE and REIMAGINE phase 3 clinical programs to investigate the efficacy of combining cagrilintide and semaglutide (CagriSema) for weight management and type 2 diabetes (T2D) treatment across a range of patient populations.

The REDEFINE program is primarily focused on assessing the weight loss potential of cagrilintide + semaglutide in individuals with and without diabetes. This program consists of six trials, five of which have been detailed [13]:

• REDEFINE 1: A 68-week trial involving 3,400 patients, comparing cagrilintide + semaglutide against monotherapies and placebo, with weight loss as the primary outcome.
• REDEFINE 2: A 68-week trial with 1,200 patients, comparing cagrilintide + semaglutide against placebo, focusing on weight loss as the primary outcome.
• REDEFINE 3: A large-scale trial involving 7,000 patients, assessing cagrilintide + semaglutide with a focus on 3-point major adverse cardiovascular events as the primary outcome.
• REDEFINE 4: A 72-week head-to-head trial involving 800 patients, comparing cagrilintide + semaglutide against tirzepatide, with weight loss as the primary outcome.
• REDEFINE 5: A 68-week trial conducted in East Asia with 330 patients, comparing cagrilintide + semaglutide against semaglutide 2.4 mg, with weight loss as the primary outcome.

In parallel, Novo Nordisk's REIMAGINE program is specifically targeting the management of T2D through the combined use of cagrilintide and semaglutide. This program encompasses four trials [14, 15, 16]:

• REIMAGINE 1: A 40-week trial involving 180 patients with T2D, comparing cagrilintide + semaglutide against placebo, with HbA1c as the primary outcome.
• REIMAGINE 2: A 68-week trial with 2,700 patients on metformin (MET) with or without SGLT-2 inhibitors, comparing cagrilintide + semaglutide against semaglutide, cagrilintide, and placebo, with both HbA1c and body weight as primary outcomes.
• REIMAGINE 3: A 40-week trial involving 270 patients with T2D on basal insulin with or without MET, assessing cagrilintide + semaglutide as an add-on therapy compared to placebo, with HbA1c as the primary outcome.
• REIMAGINE 4: A 68-week head-to-head trial with 1,000 patients on MET with or without SGLT-2 inhibitors, comparing cagrilintide + semaglutide against tirzepatide, focusing on HbA1c and body weight as primary outcomes.

These comprehensive and large-scale studies aim to establish cagrilintide + semaglutide efficacy and safety profile, potentially positioning it as a key therapeutic option for both weight management and diabetes control.

All of these trials are in the recruitment phase, and the first results are expected as soon as 2026-2027.

Cagrilintide | Side Effects

Clinical trials suggest that cagrilintide is generally well tolerated, with the most common side effects being mild to moderate, similar to those seen with GLP-1 agonists and other amylin agonists [1]. 

The largest completed and published study to date, a phase 2 trial involving 706 overweight or obese subjects, found mild to moderate gastrointestinal issues to be the most frequent side effects across different doses of cagrilintide. 

The overall discontinuation rate due to side effects across all doses was reported to be around 10%.

The following are the most common complaints experienced by the group of 101 subjects receiving the highest 4.5 mg weekly dose [11]:

• Nausea: 47 patients (47%)
• Injection-site reactions: 43 patients (43%)
• Constipation: 21 patients (21%)
• Fatigue: 20 patients (20%)
• Allergic reactions: 10 patients (10%)
• Vomiting: 8 patients (8%)
• Headache: 7 patients (7%)
• Diarrhea: 7 patients (7%)
• Dyspepsia: 4 patients (4%)
• Acute gallbladder disease: 1 patient

In total, around 88% of participants receiving the highest 4.5mg/weekly dose experienced some side effects, with 63% experiencing gastrointestinal issues specifically. Only one individual withdrew from the highest dose subgroup due to side effects.

Overall, the incidence of side effects was similar across the 2.4mg/weekly and 4.5mg/weekly groups, except for the rate of nausea, which was significantly more common with the higher dosage.

Cagrilintide Dosing | Research Only

In published studies, cagrilintide has been identified as having a safe maximum weekly dose of 4.5 mg. Researchers have typically employed a starting dose of 0.3 mg per week, with a gradual escalation every four weeks over a 16-week period to mitigate the risk of adverse effects [11].

Nevertheless, data from available trials indicate that the peptide demonstrates comparable efficacy at both 2.4 mg/week and 4.5 mg/week, particularly when co-administered with semaglutide. 

Consequently, ongoing phase 3 trials have adopted an initial dosing strategy for cagrilintide at 0.25 mg/week, akin to the approach used with semaglutide. This regimen involves a more conservative titration, reaching a maximum of 2.4 mg/week by the 16th week.

The following dosing protocol has been derived from the published data:

• Cagrilintide Dose: Previous studies have initiated treatment at 0.25 mg/week for the first four weeks, followed by increments to 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 the 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.
• Administration Frequency: Cagrilintide is administered once weekly via subcutaneous injection, typically in the abdominal area.
• Study Length: Published studies have reported durations of up to 32 weeks at 2.4 mg/week and 26 weeks at 4.5 mg/week. Phase 3 trials are planned to last up to 72 weeks.
• Important Considerations: The maximum weekly dose should not exceed 4.5 mg. It is recommended that injection sites be rotated to reduce the risk of local side effects.

Where to buy Cagrilintide online?

As researchers, obtaining high-purity peptides is paramount for ensuring the reproducibility and reliability of experimental results. Given the number of vendors offering research peptides, finding a reliable source for Cagrilintide can be challenging.

To guarantee the highest quality, our peptide review team evaluated multiple suppliers by purchasing and testing their products. Among the options, Arctic Peptides consistently stood out, offering the ability to buy Cagrilintide that meets the highest scientific standards for purity and reliability.

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