Cagrilintide

Cagrilintide is a long-acting amylin analogue peptide developed for weight management that has demonstrated significant efficacy in reducing body weight in clinical trials. This investigational compound mimics the satiety-inducing effects of natural amylin, a pancreatic hormone co-secreted with insulin. Cagrilintide has gained considerable attention among researchers, biohackers, and individuals seeking advanced weight loss solutions due to its novel mechanism of action distinct from GLP-1 receptor agonists. In clinical studies, doses ranging from 0.3 mg to 4.5 mg administered once weekly have produced dose-dependent weight loss of 6% to 10.8% over 26 weeks, with the combination therapy (CagriSema) showing even more impressive results of up to 22-24% weight reduction over 68 weeks.

What Is Cagrilintide?

Cagrilintide (also known as AM833 or NN9838) is a synthetic, long-acting analogue of human amylin, a 37-amino acid peptide hormone naturally produced by pancreatic beta cells. Developed by Novo Nordisk, cagrilintide was engineered through strategic amino acid modifications to extend its half-life, enabling once-weekly subcutaneous administration rather than the multiple daily injections required by earlier amylin analogues like pramlintide.

What makes cagrilintide unique in the weight management landscape is its distinct mechanism from the widely-used GLP-1 receptor agonists such as semaglutide. While GLP-1 agonists primarily work through incretin pathways, cagrilintide activates amylin receptors (AMY1R and AMY3R) and calcitonin receptors in the brain, providing complementary appetite-suppressing effects. This differentiation has positioned cagrilintide as both a standalone therapy and a powerful combination partner with semaglutide in the investigational product CagriSema.

The primary human-use benefits of cagrilintide include substantial weight reduction, enhanced satiety signaling, improved insulin sensitivity, and potential leptin sensitization effects. Research indicates cagrilintide functions as both an insulin and leptin sensitizer, addressing multiple metabolic pathways simultaneously.

How It Works

Amylin Receptor Activation

Cagrilintide exerts its primary effects through activation of amylin receptors, specifically AMY1R and AMY3R, located predominantly in the area postrema and nucleus of the solitary tract in the brainstem. These regions are critical for processing satiety signals and regulating food intake. When cagrilintide binds to these receptors, it triggers a cascade of neuronal signaling that promotes feelings of fullness and reduces appetite.

Calcitonin Receptor Engagement

Beyond amylin receptors, cagrilintide also demonstrates agonist activity at calcitonin receptors. Research has revealed that cagrilintide has an amylin-like binding mode but induces distinct conformational dynamics at calcitonin-family receptors compared to other peptides. This dual receptor engagement may contribute to its robust weight loss effects and distinguishes it pharmacologically from native amylin.

Gastric Emptying Modulation

Cagrilintide slows gastric emptying, prolonging the time food remains in the stomach and contributing to prolonged satiety after meals. Importantly, preclinical studies have shown that cagrilintide and GLP-1 analogues have distinct effects on gastric emptying and glucose tolerance, suggesting their mechanisms are complementary rather than redundant when used in combination.

Central Nervous System Effects

The peptide crosses into brain regions involved in energy homeostasis, where it modulates both homeostatic and hedonic aspects of eating behavior. This means cagrilintide not only reduces hunger driven by physiological need but may also decrease food cravings and reward-driven eating patterns.

Dosage Protocols

Clinical trials have evaluated cagrilintide across a range of doses from 0.3 mg to 4.5 mg administered once weekly via subcutaneous injection. The phase 2 trial published in The Lancet demonstrated dose-dependent weight loss, with higher doses generally producing greater reductions in body weight.

For monotherapy, the 2.4 mg dose has emerged as a key target, producing approximately 9.7% weight reduction by week 26 in phase 2 studies. The 4.5 mg dose showed the highest efficacy at 10.8% weight loss but with incrementally more side effects.

In combination therapy (CagriSema), both cagrilintide and semaglutide are dosed at 2.4 mg each, administered as a single once-weekly injection. The dose escalation protocol typically begins at 0.25 mg of each active component, escalating every four weeks until the full 2.4 mg dose is reached by week 16.

Dose escalation is critical for tolerability. In clinical protocols, cagrilintide monotherapy started at 0.6 mg and escalated every 2 weeks through 1.2 mg to reach 2.4 mg.

How to Use

Cagrilintide is administered via subcutaneous injection once weekly. The injection can be given in the abdomen, thigh, or upper arm, rotating injection sites to minimize local reactions. The peptide should be injected on the same day each week, though the specific time of day can vary based on individual preference.

For those using research-grade cagrilintide, proper reconstitution technique is essential (see Reconstitution section below). The injection should be administered slowly, and the site should not be rubbed afterward. Users should allow the solution to reach room temperature before injection to minimize discomfort.

Results Timelines

Based on clinical trial data, users can expect the following general timeline:

Weeks 1-4: Initial adaptation period with gradual appetite suppression beginning. Some users report reduced hunger within the first week, though significant weight changes are typically minimal during dose escalation.

Weeks 4-12: Noticeable weight loss begins as doses reach therapeutic levels. In clinical trials, meaningful separation from placebo became apparent by week 8-12.

Weeks 12-26: Continued progressive weight loss. The phase 2 trial demonstrated 6.0% to 10.8% body weight reduction by week 26 depending on dose, with the 4.5 mg group losing an average of 11.5 kg.

Weeks 26-68: In longer-term combination studies (CagriSema), weight loss continued through week 68, with participants achieving mean reductions of 22-24% of body weight.

Research Evidence

The clinical evidence base for cagrilintide has grown substantially through multiple well-designed trials:

The pivotal phase 2 trial (NCT03856047) randomized 706 participants across ten countries to various cagrilintide doses, liraglutide 3.0 mg, or placebo. All cagrilintide doses produced significantly greater weight loss than placebo (p

The REDEFINE 1 and REDEFINE 2 phase 3 trials evaluated CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) in adults with overweight/obesity with and without type 2 diabetes. Results presented in 2025 demonstrated that once-weekly CagriSema resulted in significantly lower body weight than placebo, with mean reductions exceeding 20%.

Mechanistic studies published in Nature Communications have elucidated the structural and dynamic features of cagrilintide binding to calcitonin-family receptors, providing molecular-level understanding of its pharmacology.

Additional ongoing trials (NCT07220759, NCT07220642) continue to evaluate cagrilintide's effects on weight loss in various populations including those with type 2 diabetes.

Stacking

The most clinically validated stacking approach combines cagrilintide with semaglutide, marketed investigationally as CagriSema. This combination leverages complementary mechanisms: semaglutide's GLP-1 receptor agonism and cagrilintide's amylin receptor activation.

Network meta-analyses have confirmed that CagriSema produces the largest reductions in both body weight and waist circumference compared to either agent alone.

The rationale for this combination extends beyond additive effects. Preclinical research suggests cagrilintide and GLP-1 analogues work through distinct pathways affecting gastric emptying and glucose tolerance, meaning their combination addresses multiple physiological targets simultaneously.

For research purposes, some investigators have explored cagrilintide alongside other metabolic peptides, though clinical data supporting such combinations remains limited.

Reconstitution, Storage & Prep

Research-grade cagrilintide typically arrives as a lyophilized (freeze-dried) powder requiring reconstitution before use.

Reconstitution: Use bacteriostatic water (BAC water) for reconstitution. The amount of BAC water added determines the concentration. For example, adding 2 mL of BAC water to a 5 mg vial yields a concentration of 2.5 mg/mL. Inject the water slowly down the side of the vial, allowing it to gently dissolve the powder. Do not shake vigorously; instead, swirl gently or allow to sit until fully dissolved.

Storage: Unreconstituted lyophilized cagrilintide should be stored in a freezer (-20°C) for long-term storage or refrigerated (2-8°C) for shorter periods. Once reconstituted, the solution must be refrigerated and is typically stable for 4-6 weeks, though some degradation may occur over time. Never freeze reconstituted peptide solutions.

Preparation: Before injection, allow the vial to reach room temperature. Draw the appropriate dose using an insulin syringe, ensuring no air bubbles are present. Clean the injection site with an alcohol swab before administration.

Side Effects

The safety profile of cagrilintide has been characterized across multiple clinical trials. The most commonly reported adverse events are gastrointestinal in nature:

Gastrointestinal effects: Nausea is the most frequent side effect, reported in 20-47% of participants depending on dose (compared to 18% with placebo). Constipation, diarrhea, and vomiting also occur with increased frequency. These effects are typically mild to moderate and tend to diminish over time as the body adapts.

Injection site reactions: Local reactions at the administration site, including redness, swelling, or itching, have been reported. Rotating injection sites helps minimize these effects.

Decreased appetite: While therapeutically desired, some users may experience appetite suppression that feels excessive, particularly during dose escalation.

Combination therapy considerations: When cagrilintide is combined with semaglutide (CagriSema), gastrointestinal adverse events occur more frequently than with either agent alone. In the REDEFINE trials, any GI event occurred in approximately 79.6% of CagriSema participants versus 39.9% on placebo.

Most adverse events were mild to moderate in severity, and discontinuation rates due to adverse events remained relatively low across trials (approximately 4%).

Legal Status / FDA

Cagrilintide is not currently approved by the U.S. Food and Drug Administration (FDA) for any indication. It remains an investigational compound undergoing clinical development.

The FDA has explicitly stated that cagrilintide cannot be used in compounding under federal law, as it is not a component of any FDA-approved drug and has not been evaluated for safety and efficacy outside of clinical trials.

Novo Nordisk has filed for FDA approval of CagriSema (the fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg), with the FDA expected to review the application in 2026.

Currently, cagrilintide is available only through clinical trials or as a research chemical sold for laboratory and research purposes only, not for human consumption.

Sports/WADA

The World Anti-Doping Agency (WADA) maintains a Prohibited List that is updated annually. Peptide hormones and their analogues fall under the category of prohibited substances in sport.

While cagrilintide is not specifically named on the WADA Prohibited List, it would likely fall under the prohibition of peptide hormones, growth factors, and related substances. Athletes subject to anti-doping regulations should assume cagrilintide is prohibited and consult GlobalDRO.com or their sport's anti-doping authority for definitive guidance.

Any athlete considering use of cagrilintide should be aware that detection methods for peptide hormones continue to advance, and the use of unapproved investigational compounds carries significant risks both to athletic eligibility and health.

Conclusion

Cagrilintide represents a significant advancement in peptide-based approaches to weight management, offering a novel mechanism of action through amylin and calcitonin receptor agonism. Clinical evidence demonstrates meaningful weight loss efficacy both as monotherapy and in combination with semaglutide, with the CagriSema combination showing particularly impressive results exceeding 20% body weight reduction in phase 3 trials.

The once-weekly dosing schedule, established safety profile, and complementary mechanism to existing GLP-1 therapies position cagrilintide as a potentially valuable addition to the metabolic peptide landscape. However, its current investigational status means it is not approved for human use outside of clinical trials, and individuals should carefully consider the legal and safety implications of using unapproved compounds.

As regulatory review of CagriSema proceeds in 2026, cagrilintide may soon transition from investigational compound to approved therapy, potentially offering new options for individuals struggling with obesity and related metabolic conditions.

FAQ

What is the difference between cagrilintide and semaglutide?
Cagrilintide is an amylin analogue that works primarily through amylin and calcitonin receptors in the brain, while semaglutide is a GLP-1 receptor agonist that works through incretin pathways. They have complementary mechanisms, which is why their combination (CagriSema) produces greater weight loss than either alone.

How much weight can I expect to lose with cagrilintide?
Clinical trials have shown weight loss ranging from 6% to 10.8% of body weight over 26 weeks with cagrilintide monotherapy, depending on dose. The combination with semaglutide (CagriSema) has demonstrated weight reductions of 22-24% over 68 weeks.

Is cagrilintide FDA approved?
No, cagrilintide is not currently FDA approved. It remains an investigational compound. Novo Nordisk has filed for FDA approval of CagriSema, with review expected in 2026.

What are the most common side effects of cagrilintide?
Gastrointestinal side effects are most common, including nausea (20-47% of users), constipation, diarrhea, and vomiting. Injection site reactions may also occur. Most side effects are mild to moderate and tend to improve over time.

How often is cagrilintide injected?
Cagrilintide is administered once weekly via subcutaneous injection, making it more convenient than earlier amylin analogues that required multiple daily injections.

Can cagrilintide be used with other weight loss medications?
The most studied combination is cagrilintide with semaglutide (CagriSema). This combination has shown superior efficacy compared to either agent alone. Other combinations have not been extensively studied in clinical trials.

How should cagrilintide be stored?
Lyophilized (powder) cagrilintide should be stored frozen or refrigerated. Once reconstituted with bacteriostatic water, it must be refrigerated and used within 4-6 weeks.

Is cagrilintide banned in sports?
While not specifically named, cagrilintide would likely fall under WADA's prohibition of peptide hormones. Athletes should assume it is prohibited and verify with their sport's anti-doping authority.