Cagrilintide | Side Effects, Complications, and Risk Profile

Cagrilintide's side effects are of particular interest to researchers, given its novel composition and significant potential across multiple research areas, including:

• Chronic weight management in overweight and obese individuals
• Glycemic control in type 2 diabetes
• Synergy with other weight loss peptides

This guide provides a comprehensive overview of the primary side effects associated with cagrilintide based on current research.

Additionally, it offers crucial insights into proper dosing and administration strategies to minimize cagrilintide-related risks during research.

Researchers will also find recommendations for the most reliable source for purchasing research-grade cagrilintide online.

What is Cagrilintide | Overview

Cagrilintide is a novel synthetic peptide analog of the human hormone amylin. Amylin (islet amyloid polypeptide) is a 37-amino-acid peptide co-secreted with insulin by the pancreas that plays a crucial role in [1]:

• The suppression of glucagon after a meal
• Slowing of gastric emptying
• Promoting satiety

Cagrilintide targets the amylin receptor, which is part of a class of receptors that also responds to calcitonin and calcitonin gene-related peptides.

In turn, calcitonin is a thyroid hormone that regulates calcium homeostasis, but also its receptors play a role in blood sugar level regulation especially in diabetic conditions [2]. Cagrilintide also activates the calcitonin receptors, making it a dual amylin and calcitonin receptor agonist (DACRA).

Here is what researchers should know about this peptide [3]:

• Cagrilintide was developed in the 2010s by the Danish pharmaceutical company Novo Nordisk to enhance the natural effects of amylin in activating the aforementioned receptors, regulating glucose levels, and reducing appetite.
• Cagrilintide's design involves several modifications that allow for an extended half-life and improved receptor activity compared to endogenous amylin. This includes several amino acid substitutions and an attachment of a C-20 fatty di-acid moiety.
• Thanks to the modifications and the affinity of the C-20 fatty di-acid moiety to serum albumin, Cagrilintide's pharmacokinetics include a half-life of 7.3 days that supports once-weekly subcutaneous administration.
• The therapeutic application of cagrilintide primarily focuses on weight management and the treatment of obesity, and obesity-related conditions such as type 2 diabetes (T2D).

Currently, the peptide is not approved by the Food and Drug Administration (FDA) but it is under active investigation by several phase 3 clinical trials in combination with semaglutide (a GLP-1 receptor agonist already FDA-approved for weight management) [3, 4].

The combination of cagrilintide with semaglutide (trade name CagriSema) aims to leverage the synergistic effects of both peptides on satiety and glycemic control, offering a comprehensive approach to treating these metabolic disorders [5].

The trials have shown promising results in clinical trials, suggesting a potential path forward for its use in obesity management and type 2 diabetes treatment.

In addition, the peptide is also available for laboratory use by qualified professionals.

Research Applications and Benefits of Cagrilintide | Overview

The following summary highlights significant research applications of cagrilintide based on recent clinical trials.

Cagrilintide for Weight Loss Research

A phase 1b, randomized, placebo-controlled trial investigated the effectiveness of combining cagrilintide with the GLP-1 analog semaglutide for weight management. This 20-week study included 96 non-diabetic individuals aged 18–55 years with overweight or obesity.

Participants were divided into six sequential overlapping cohorts, each receiving different doses of cagrilintide (0.16, 0.30, 0.60, 1.2, 2.4, and 4.5mg/weekly) combined with a semaglutide of 2.4mg/weekly.

Each cohort was compared against a matched control group that received placebo injections alongside semaglutide. The researchers reported the following results [6]:

• The 1.2mg/weekly and 2.4mg/weekly doses of cagrilintide combined with semaglutide led to mean percentage body weight reductions of -15.7% and -17.1%, respectively, versus -9.8% with pooled placebo+semaglutide cohorts.
• The highest dose, 4.5mg/weekly cagrilintide combined with semaglutide, resulted in a -15.4% weight reduction, compared to an -8% reduction in the matched placebo+semaglutide cohorts.
• Both 2.4mg/weekly and 4.5mg/weekly cagrilintide led to -7.4% greater weight loss compared to placebo (semaglutide alone).

In a phase 2 trial, 706 non-diabetic individuals with overweight or obesity were randomly assigned to receive either various weekly doses of cagrilintide (0.3mg to 4.5mg), a GLP-1 agonist liraglutide administered at 3mg/daily, or a placebo.

Here is a summary of the results [7]:

• All doses of cagrilintide resulted in significant weight loss over a 26-week period, with mean percentage weight reductions from baseline ranging between -6% to -10.8% across different doses, compared to a -3.0% with placebo.
• The highest dose of cagrilintide (4.5mg/weekly) showed a greater weight reduction (-10.8%) compared to liraglutide 3mg/daily (-9%).

Currently, cagrilintide combined with semaglutide is under investigation for its weight loss potential in the phase 3 clinical program initiated by Novo Nordisk and called REDEFINE.

The program consists of several trials that investigate the weight loss effects of the combination in patients with overweight, obesity, diabetes, cardiovascular diseases, and more [8].

Cagrilintide for Glycemic Control Research

Cagrilintide has been studied for its effectiveness in controlling blood sugar levels in T2D patients, both as a standalone therapy or in combination with semaglutide.

A phase 2, 32-week, multicenter, double-blind trial was conducted to examine the effectiveness of a combination of cagrilintide and semaglutide (trade name CagriSema), in adults with T2D and overweight or obesity.

The participants were assigned in a 1:1:1 ratio to cagrilintide + semaglutide, semaglutide alone, or cagrilintide alone, and all dosages were escalated up to 2.4mg/weekly. The trial led to the following findings [9]:

• From baseline to week 32, cagrilintide + semaglutide led to a significant reduction in HbA1c by –2.2%, while cagrilintide alone also led to –0.9% reduction.
• The reduction in body weight was highest in the cagrilintide + semaglutide group (–15.6%) followed by the cagrilintide (–8.1%) and semaglutide (–5.1%) groups.
• The reduction in fasting glucose was greatest with cagrilintide + semaglutide (–3.3 mmol/L), followed by semaglutide (–2.5 mmol/L) and cagrilintide (–1.7 mmol/L). The comparison was statistically significant against cagrilintide but not semaglutide.

Overall, cagrilintide appears to be highly effective in boosting the weight loss and anti-diabetic properties of the GLP-1 agonist semaglutide.

Following these findings, the combination of cagrilintide and semaglutide has been incorporated into a phase 3 clinical program called REIMAGINE.

The program was initiated by Novo Nordisk and aims to further investigate the potential of the combination for T2D management. Currently, there are three out of four trials underway and actively recruiting participants [10, 11, 12].

Side effects of Cagrilintide

As of 2024, cagrilintide has not been approved for human use and is currently being evaluated in phase 3 clinical trials alongside semaglutide.

Previous phase 1 and phase 2 trials indicate that cagrilintide is well-tolerated, with a safety profile similar to other amylin analogs that already hold FDA approval such as pramlintide [1].

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

All of these side effects were resolved successfully. The overall discontinuation rate due to side effects was around 10% [7].

Common side effects

The largest published study to date, a phase 2 trial involving 706 overweight or obese subjects, found that side effects were common across all doses, which ranged from 0.3 to 4.5mg/weekly.

At the highest dosage, 88% of participants experienced side effects, with 63% specifically reporting gastrointestinal issues. Only one participant withdrew from this subgroup due to side effects.

Among the 101 subjects receiving the highest 4.5mg/weekly dose, the most common complaints were [7]:

• Nausea: 47%
• Reactions at the injection site: 43%
• Tiredness: 20%
• Constipation: 21%
• Allergic reactions: 10%
• Vomiting: 8%
• Headache: 7%
• Loose stools: 7%
• Dyspepsia: 4%

The majority of these side effects were temporary and manageable via a slower increase in weekly dosage. Furthermore, side effects like constipation can also be reduced by lifestyle changes such as increased hydration, fiber intake, and physical activity.

Serious Side Effects

The available phase 1 and phase 2 trials report that serious side effects are extremely rare with cagrilintide and do not depend on the dose.

Their incidence of serious side effects in the largest phase 2 trial ranged between 2-7% amongst the cagrilintide groups, compared to 4% in the liraglutide group and 3% in the placebo group [7].

One side effect potentially linked to cagrilintide was acute cholelithiasis (gallbladder stones) which occurred in one subject receiving 4.5mg/weekly of the peptide.

Cagrilintide was also noted to induce the production of anti-cagrilintide antibodies, and their presence increased with both the dose and duration of exposure, affecting 46–73% of participants by week 26.

Yet, the presence and levels of these antibodies did not appear to impact changes in body weight and most importantly, no serious allergic reactions were reported [7].

General Risks and Complications

Cagrilintide remains unapproved for human use as of 2024 and is currently undergoing evaluation in a phase 3 clinical trial alongside semaglutide.

Based on data from earlier phase 1 and phase 2 trials, cagrilintide has shown to be well-tolerated with a safety profile consistent with those of FDA-approved GLP-1 agonists such as semaglutide and liraglutide, as well as FDA-approved amylin analogs like pramlintide [1].

The primary adverse events are gastrointestinal, with mild to moderate nausea being the most common. This nausea is typically temporary, dose-dependent, and manageable [7].

Additional effects such as constipation may occur due to amylin analog effects on slowing gastric emptying, but these are manageable through strategies such as prolonging the dose escalation period and ensuring sufficient hydration.

The ongoing phase-3 clinical program is expected to provide more extensive data on both the efficacy and safety of cagrilintide in combination with semaglutide.

Recommended Dosage for Cagrilintide Research Only

Based on the available phase 2 studies, cagrilintide is typically dosed once weekly thanks to its extensive half-life, and the maximum dosage may reach up to 4.5mg/weekly when used alone, or up to 2.4mg/weekly when combined with semaglutide [6, 7].

Currently, the ongoing phase 3 trials with cagrilintide are dosing the peptide alongside semaglutide with a starting dose of 0.25mg/weekly and achieve a maximum dosage of 2.4mg/weekly over 17 weeks [8]. In this scenario, a potential increase in dosage up to 4.5mg/weekly should occur only after the 21st week.

The following dosing protocol is provided as a reference for the investigation of cagrilintide's efficacy in weight management among obese participants in ongoing phase 3 trials:

• Cagrilintide Weekly Dose: Researchers start with a dose of 0.25mg/weekly for the initial four weeks, then escalate to 0.5mg/weekly for weeks 5-8, progress to 1mg/weekly for weeks 9-12, increase to 1.7mg/weekly for weeks 13-16, and finally reach a maintenance dose of 2.4mg/weekly from week 17 onwards.
• Administration Frequency: Once a week, via subcutaneous injection, typically within the abdominal region.
• Study Length: Published trials have lasted up to 32 weeks at 2.4mg/weekly and 26 weeks at 4.5mg/weekly.
• Notes: The maximum weekly dose should not exceed 4.5mg. Injection sites must be rotated to minimize local side effects.

Where to Buy Cagrilintide Online? | 2024 Edition

For researchers, buying peptides of high purity is essential for maintaining the precision and reliability of experimental results. However, with numerous suppliers in the market, finding a trustworthy source for Cagrilintide can be a difficult task.

Following an extensive evaluation of several vendors, our review team concluded that Arctic Peptides consistently offers high-quality Cagrilintide that meets the strictest scientific criteria for purity and dependability

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