Cagrilintide | Dosage Calculator and Chart
Cagrilintide is a novel peptide being studied for its potential to reduce appetite, promote weight loss, and improve glycemic control by targeting amylin and calcitonin receptors.
This peptide is still in clinical investigation, and researchers are likely still refining its optimal dosage due to its novel mechanism of action.
To fully leverage cagrilintide’s therapeutic potential, staying updated on the latest research is crucial. This detailed guide aims to provide scientists with valuable insights for effective cagrilintide experimentation.
What is Cagrilintide?
Cagrilintide, referred to as AM833, is a peptide engineered by Novo Nordisk aimed at addressing obesity and type 2 diabetes (T2D).
This compound is a modified form of amylin, a 37-amino-acid hormone that is co-released with insulin by the pancreas. Amylin plays a key role in delaying gastric emptying, regulating postprandial glucagon secretion and enhancing feelings of fullness [1].
As a dual amylin and calcitonin receptor agonist (DACRA), Cagrilintide engages both amylin and calcitonin receptors, amplifying its therapeutic potential.
What Should Researchers Know
- The hormone calcitonin, produced by the thyroid gland, is primarily involved in regulating calcium balance by promoting calcium incorporation into bones. Studies suggest that stimulating its receptors with peptides like cagrilintide may also help reduce blood glucose levels in T2D [2].
- In the brain, cagrilintide targets amylin receptors located in key areas that regulate appetite, including the nucleus tractus solitarius (NTS) and the area postrema (AP). This action could lead to decreased food consumption and contribute to weight reduction [3].
- By activating these receptors, cagrilintide additionally slows the rate of gastric emptying and suppresses glucagon secretion, which prolongs the sensation of satiety after eating and aids in maintaining stable blood glucose levels. This supports weight control and improves metabolic health overall [4].
- The peptide’s therapeutic durability is further enhanced by several amino acid modifications and the attachment of a C-20 fatty di-acid via an α-glutamyl spacer, which extends its half-life to roughly 7.3 days, allowing for weekly subcutaneous administration [5].
Cagrilintide is currently being evaluated in phase 3 clinical trials (REDEFINE and REIMAGINE) in combination with semaglutide, marketed under the name CagriSema [5, 6].
Developed by Novo Nordisk, semaglutide has already received FDA approval for controlling blood sugar, reducing cardiovascular risks in T2D patients, and treating obesity in individuals aged 12 and older [7, 8].
Semaglutide mimics the action of the incretin hormone GLP-1, triggering insulin secretion and curbing appetite, with a half-life lasting more than a week.
Since GLP-1 receptors are located on a distinct set of appetite-regulating neurons in the brain, the combination of cagrilintide and semaglutide has the potential to further amplify appetite suppression [9].
Cagrilintide has not yet received approval from the U.S. Food and Drug Administration (FDA) and is currently available only for research purposes to qualified professionals.
Benefits of Cagrilintide
The ongoing phase 3 clinical trials from the REDEFINE and REIMAGINE programs aim to deliver the most extensive data on the combined effects of cagrilintide and semaglutide for weight loss and type 2 diabetes (T2D) management.
Different trials have projected completion dates ranging from 2025 to 2027. In the meantime, results from earlier trials provide insight into the key benefits observed so far:
Appetite suppression and weight reduction: A 26-week phase 2 study, involving 706 overweight and obese participants without T2D, showed a weight reduction of -9.7% (-22.7 lb) with 2.4 mg/week and -10.8% (-25.4 lb) with 4.5 mg/week of cagrilintide. For comparison, 3 mg/day of liraglutide resulted in -9% weight loss from baseline [11].
Synergistic weight loss potential with GLP-1 agonists: In a 20-week phase 1b trial involving 96 overweight and obese participants without T2D, a combination of 2.4 mg/week cagrilintide and semaglutide led to a -17.1% reduction in baseline body weight. Both the 2.4 mg/week and 4.5 mg/week cagrilintide + semaglutide groups demonstrated an additional -7.4% weight loss compared to the semaglutide-only group [10].
Improved blood sugar control and weight loss in T2D: A 32-week phase 2 trial, involving 92 participants with T2D, revealed that weekly doses of 2.4 mg cagrilintide + semaglutide reduced HbA1c levels by -2.2%, fasting blood sugar by -3.3 mmol/L, and body weight by -15.6% from baseline [12].
Across all studies, the combination of cagrilintide and semaglutide showed superior results compared to either compound alone. While cagrilintide at 2.4 mg/week was linked to more significant weight loss, its anti-diabetic effects were slightly weaker compared to semaglutide at the same dose.
Side Effects of Cagrilintide
Side effects observed in cagrilintide trials tend to be dose-dependent, with gastrointestinal issues being the most frequently reported.
These effects are usually temporary and can often be managed by slowly increasing the weekly dose. Additionally, lifestyle modifications, such as staying hydrated, increasing fiber intake, and maintaining regular physical activity, may help ease side effects like constipation.
In the largest trial conducted so far, a phase 2 study involving 706 overweight or obese participants, side effects were common across all dosage levels, ranging from 0.3 to 4.5 mg/week [11].
At the highest dosage, 88% of participants reported side effects, with gastrointestinal problems affecting 63%. Only one participant in the 4.5 mg/week group discontinued due to adverse effects.
Among the 101 participants receiving the highest 4.5 mg/week dose, the most frequently reported side effects included:
- Indigestion: 4%
- Headache: 7%
- Loose stools: 7%
- Vomiting: 8%
- Allergic reactions: 10%
- Fatigue: 20%
- Constipation: 21%
- Injection site reactions: 43%
- Nausea: 47%
Serious side effects in this phase 2 trial occurred in 2% to 7% of the cagrilintide groups, compared to 4% in the liraglutide group and 3% in the placebo group.
One participant on the 4.5 mg/week dose developed acute cholelithiasis (gallstones), which may be related to cagrilintide use.
All side effects were resolved successfully, and the overall discontinuation rate due to side effects across all doses was around 10% [11].
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 | 0.25mg | 0.5mg | 1mg | 1.7mg | 2.4mg |
Recommended Dosage for Cagrilintide Research
Extensive clinical trial data suggest that cagrilintide provides substantial benefits when used appropriately in research settings.
This peptide has been investigated in areas such as weight loss, blood glucose regulation, and cardiovascular effects.
Cagrilintide Dosage for Weight Management Research
Cagrilintide is actively being studied for its potential to promote weight loss in individuals without type 2 diabetes (T2D). In phase 1b and phase 2 weight loss trials, the peptide has been administered both as a monotherapy and in combination with semaglutide.
In a 20-week phase 1b study involving overweight and obese participants, six different weekly doses of cagrilintide (0.16, 0.3, 0.6, 1.2, 2.4, and 4.5 mg) were tested alongside 2.4 mg/week semaglutide, with a control group receiving only semaglutide.
Researchers initiated treatment at doses approximately ten times lower, gradually increasing them every four weeks for a total of 16 weeks. The higher doses of 1.2, 2.4, and 4.5 mg/week cagrilintide combined with semaglutide were more effective than semaglutide alone. The combination of 2.4 mg/week cagrilintide with semaglutide led to the most significant weight loss (-17.1% from baseline), and both the 2.4 and 4.5 mg/week doses showed an identical placebo-adjusted weight reduction of -7.4% [10].
In a larger phase 2 study involving 706 overweight and obese participants, cagrilintide was administered without semaglutide and compared to the FDA-approved GLP-1 agonist liraglutide.
Two groups received consistent weekly doses of 0.3 mg and 0.6 mg throughout the 26-week study, while three groups saw their dosages escalated every two weeks to reach 1.2, 2.4, and 4.5 mg/week. Both the 1.2 and 2.4 mg doses had similar weight loss results to daily liraglutide, while the 4.5 mg cagrilintide was notably more effective.
Ongoing phase 3 trials for weight loss in non-T2D individuals are now utilizing a similar dosing protocol to that of semaglutide, starting at 0.25 mg/week with gradual titration every four weeks, up to a maximum of 2.4 mg/week [11].
Cagrilintide Dosage for Diabetes Research
Cagrilintide has also been studied for its ability to manage blood sugar in patients with type 2 diabetes (T2D) but only when used in combination with semaglutide. In a 32-week phase 2 trial, the effectiveness of cagrilintide paired with semaglutide was compared to either peptide alone in 92 T2D patients.
Here’s a breakdown of the dosing and findings from this trial [12]:
The participants in the three groups (cagrilintide + semaglutide, semaglutide alone, and cagrilintide alone) followed a dosing regimen that involved increasing the dosage every four weeks, starting from 0.25 mg and moving up to 0.5 mg, 1.0 mg, and 1.7 mg until reaching the final dose of 2.4 mg/week at the 16-week mark.
After reaching the target dose, the 2.4 mg/week dose was sustained for an additional 16 weeks. The highest weight loss was observed in the combination group of cagrilintide + semaglutide (-15.6% from baseline), with cagrilintide alone resulting in -8.1%, and semaglutide alone achieving -5.1%.
In terms of blood sugar control, fasting glucose dropped the most in the combination group (-3.3 mmol/L), followed by semaglutide (-2.5 mmol/L) and cagrilintide (-1.7 mmol/L). The ongoing phase 3 REIMAGINE clinical trials, designed for T2D patients, utilize the same 16-week dosing escalation protocol, with a maximum dose of 2.4 mg/week for both cagrilintide and semaglutide [13, 14].
Among these, the largest trial, REIMAGINE 2, will run for 68 weeks, including a 16-week dose escalation period followed by 52 weeks of maintenance, enrolling 2,700 T2D patients on metformin (MET), with or without SGLT-2 inhibitors. The trial will assess cagrilintide + semaglutide versus semaglutide alone, cagrilintide alone, and placebo, using both glycated hemoglobin (HbA1c) and body weight as primary outcomes [15].
Cagrilintide Dosage for Other Research Objectives
Building on the findings from earlier trials, the REDEFINE phase 3 clinical program by Novo Nordisk further investigates the weight loss potential of cagrilintide combined with semaglutide across different patient groups [16].
As part of this program, REDEFINE-3 is specifically designed to assess the cardiovascular benefits of cagrilintide and its impact on major adverse cardiovascular events (MACE). The trial aims to recruit 7,000 overweight or obese participants, including those with and without type 2 diabetes.
Currently, in the recruitment phase as of 2024, REDEFINE-3 will use a dosing schedule similar to other REDEFINE and REIMAGINE trials. Participants will start with 0.25 mg/week, escalating every four weeks to 0.5 mg, 1.0 mg, and 1.7 mg, before reaching the final maintenance dose of 2.4 mg/week after 16 weeks. The study is expected to continue for up to 4.5 years [17].
Cagrilintide Dosage Calculator
Due to its extended half-life, cagrilintide is typically given once per week. When used on its own, the maximum dosage is 4.5 mg weekly, whereas in combination with semaglutide, the dose is capped at 2.4 mg per week [10, 11].
In ongoing phase 3 clinical trials, dosing starts at 0.25 mg per week alongside semaglutide, with gradual increases reaching a maximum of 2.4 mg weekly by the 17th week, following a 16-week dose-escalation protocol [16].
Researchers may consider increasing the dosage up to 4.5 mg per week after week 21, depending on study needs.
Here’s the dosing framework used to evaluate cagrilintide’s efficacy in weight management studies for obesity:
- Weekly Dose Escalation: Research begins with a weekly dose of 0.25 mg for the first 4 weeks. During weeks 5-8, the dose is increased to 0.5 mg. From weeks 9-12, participants receive 1 mg per week, followed by 1.7 mg weekly in weeks 13-16. Starting at week 17, a stable dose of 2.4 mg per week is maintained.
- Administration: The drug is administered via a subcutaneous injection once a week, commonly in the abdomen.
- Study Length: Published trials have documented a duration of up to 32 weeks for the 2.4 mg dose, while for the 4.5 mg dose, studies lasted up to 26 weeks. Ongoing research is projected to last up to 4.5 years with participants receiving 2.4 mg per week.
- Note: Weekly doses should not exceed 4.5 mg, and rotating injection sites is recommended to lower the risk of localized adverse effects.
Safety Considerations and Contraindications
By 2024, cagrilintide has yet to receive approval for human use, with its safety and efficacy currently under review in phase 3 clinical trials in combination with semaglutide.
Earlier phase 1 and 2 studies demonstrated that cagrilintide was well-tolerated, exhibiting a safety profile consistent with FDA-approved GLP-1 receptor agonists like semaglutide and liraglutide, as well as the amylin analog pramlintide [1].
A key observation was the production of anti-cagrilintide antibodies, with increased incidence correlating with higher doses and prolonged exposure, affecting 46% to 73% of participants by week 26.
However, these antibodies did not seem to impact weight reduction, and no severe allergic reactions were reported [11].
The ongoing phase 3 trials, conducted under the REIMAGINE and REDEFINE programs, are expected to deliver more comprehensive data on the safety and side effect profile of cagrilintide when used in conjunction with semaglutide.
Where to Buy Cagrilintide Online | 2024 Edition
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References
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- Larsen AT, Sonne N, Andreassen KV, Karsdal MA, Henriksen K. The Calcitonin Receptor Plays a Major Role in Glucose Regulation as a Function of Dual Amylin and Calcitonin Receptor Agonist Therapy. J Pharmacol Exp Ther. 2020 Jul;374(1):74-83. doi: 10.1124/jpet.119.263392. Epub 2020 Apr 21. PMID: 32317372.
- Züger D, Forster K, Lutz TA, Riediger T. Amylin and GLP-1 target different populations of area postrema neurons that are both modulated by nutrient stimuli. Physiol Behav. 2013 Mar 15;112-113:61-9. doi: 10.1016/j.physbeh.2013.02.006. Epub 2013 Feb 21. PMID: 23438370.
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- Aroda VR, Blonde L, Pratley RE. A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Rev Endocr Metab Disord. 2022 Oct;23(5):979-994. doi: 10.1007/s11154-022-09735-8. Epub 2022 Jul 15. PMID: 35838946; PMCID: PMC9515042.
- Berman C, Vidmar AP, Chao LC. Glucagon-like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes in Youth. touchREV Endocrinol. 2023 May;19(1):38-45. doi: 10.17925/EE.2023.19.1.38. Epub 2023 May 23. PMID: 37313232; PMCID: PMC10258616.
- D'Ascanio AM, Mullally JA, Frishman WH. Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. Cardiol Rev. 2024 Jan-Feb 01;32(1):83-90. doi: 10.1097/CRD.0000000000000513. Epub 2023 Oct 20. PMID: 36883831.
- Enebo LB, Berthelsen KK, Kankam M, Lund MT, Rubino DM, Satylganova A, Lau DCW. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021 May 8;397(10286):1736-1748. doi: 10.1016/S0140-6736(21)00845-X. Epub 2021 Apr 22. PMID: 33894838.
- Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, Pedersen SD, Pietiläinen KH, Rubino D, Batterham RL. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet. 2021 Dec 11;398(10317):2160-2172. doi: 10.1016/S0140-6736(21)01751-7. Epub 2021 Nov 16. PMID: 34798060.
- Frias JP, Deenadayalan S, Erichsen L, Knop FK, Lingvay I, Macura S, Mathieu C, Pedersen SD, Davies M. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023 Aug 26;402(10403):720-730. doi: 10.1016/S0140-6736(23)01163-7. Epub 2023 Jun 23. PMID: 37364590.
- National Library of Medicine (U.S.). (n.d.). A research study to see how much CagriSema lowers blood sugar and body weight compared to placebo in people with type 2 diabetes treated with diet and exercise (REIMAGINE 1). Identifier NCT06323174. https://clinicaltrials.gov/study/NCT06323174
- National Library of Medicine (U.S.). (n.d.). A research study to see how much CagriSema lowers blood sugar and body weight compared to placebo in people with type 2 diabetes treated with once-daily basal insulin with or without metformin (REIMAGINE 3). Identifier NCT06323161. https://clinicaltrials.gov/study/NCT06323161
- National Library of Medicine (U.S.). (n.d.). A research study to see how well CagriSema compared to semaglutide, cagrilintide, and placebo lowers blood sugar and body weight in people with type 2 diabetes treated with metformin with or without an SGLT2 inhibitor (REIMAGINE 2). Identifier NCT06065540. https://clinicaltrials.gov/study/NCT06065540
- Bailey CJ, Flatt PR, Conlon JM. Recent advances in peptide-based therapies for obesity and type 2 diabetes. Peptides. 2024 Mar;173:171149. doi: 10.1016/j.peptides.2024.171149. Epub 2024 Jan 5. PMID: 38184193.
- National Library of Medicine (U.S.). (n.d.). REDEFINE 3: A Research Study to See the Effects of CagriSema in People Living With Diseases in the Heart and Blood Vessels (REDEFINE 3). Identifier NCT05669755. https://clinicaltrials.gov/study/NCT05669755