Cagrilintide vs. Tirzepatide | Best Weight Loss Peptide

This guide offers a head-to-head comparison of cagrilintide vs tirzepatide for weight loss research, making it a useful resource for professionals in academic or scientific fields.

Cagrilintide and tirzepatide are two innovative compounds with distinct mechanisms but similar research potential, particularly in areas such as:

• Weight loss in non-diabetics
• Chronic weight management in diabetics
• Glycemic control in diabetics

Both peptides act as dual receptor agonists. Cagrilintide targets the amylin and calcitonin receptors, while tirzepatide mimics two incretin hormones.

Currently, tirzepatide has received regulatory approval for two different uses, whereas cagrilintide remains in phase 3 trials, showing promise for enhancing the effectiveness of other incretin mimetics.

This guide, prepared by our expert team, provides a thorough comparison of cagrilintide and tirzepatide to assist researchers in determining which peptide to prioritize in their future studies.

What is Tirzepatide?

Tirzepatide, previously identified as LY3298176, is a pioneering dual GIP/GLP-1 agonist developed by Eli Lilly and Co., a leading American pharmaceutical company. It is intended as a treatment for obesity-related weight loss and glycemic control in type 2 diabetes (T2D).

Tirzepatide is a 39-amino-acid peptide that leverages the functions of two naturally occurring human hormones.

These hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are released by endocrine cells in the digestive system in response to food intake. They play a crucial role in stimulating insulin production and managing appetite [1, 2].

Tirzepatide works by mimicking these hormones, thereby activating their receptors in various tissues and organs, leading to:

• Stimulation of insulin production and reduction of glucagon secretion in the pancreas, helping to regulate blood sugar levels.
• Appetite suppression and reduced cravings in the brain due to receptor activation.
• Enhanced fat mobilization in fat tissue, along with modulation of hormonal and inflammatory markers associated with metabolic health and weight management.

Tirzepatide achieves receptor activation through a modified GIP sequence at its N-terminus, combined with a C-terminus sequence derived from the GLP-1 agonist exenatide. Additionally, it is enhanced by a hydrophilic linker and a C20 fatty di-acid element that extends its half-life to five days [3, 4].

Given its pharmacokinetic profile and potential therapeutic benefits, Eli Lilly has pursued several applications for tirzepatide, with the peptide already receiving multiple approvals from the United States Food and Drug Administration (US FDA).

Here is a brief timeline of tirzepatide’s development and approval [1, 5, 6]:

• In 2016, Eli Lilly secured a patent for tirzepatide.
• In 2022, tirzepatide was approved by the FDA for managing T2D, following positive outcomes from several phase 3 clinical trials within the SURPASS clinical development program. It is marketed as Mounjaro.
• In 2023, tirzepatide received FDA approval for weight loss treatment, based on phase 3 trials from the SURMOUNT clinical development program. It is marketed as Zepbound.
• As of 2024, Eli Lilly is conducting a phase 3 trial known as SURPASS-CVOT, which investigates the cardiovascular benefits of tirzepatide in patients with T2D.

What is Cagrilintide?

Cagrilintide is a synthetic peptide created and currently being studied by Novo Nordisk [7]. The research focuses on its potential to enhance weight loss and anti-diabetic benefits when used alongside GLP-1 agonists like semaglutide, an FDA-approved peptide.

Key details about the peptide include:

• Cagrilintide is structurally based on the 37-amino-acid hormone amylin, also known as islet amyloid polypeptide. Amylin is naturally secreted by the pancreas alongside insulin after meals to reduce glucagon levels, slow gastric emptying, and promote a sense of fullness [8].

• Cagrilintide’s receptor activity surpasses that of natural amylin due to specific amino acid modifications and the addition of a C-20 fatty di-acid group. These changes extend its half-life to 7.3 days, making it suitable for once-weekly subcutaneous injections [7].

• Cagrilintide functions as a dual agonist for amylin receptors (AMYRs) and calcitonin receptors (CTRs), both of which are prevalent in brain regions associated with appetite and reward. Activation of these receptors by cagrilintide results in decreased hunger and reduced food intake [9, 10].

• Through these receptors, cagrilintide temporarily slows gastric emptying, extending satiety post-meal and stabilizing blood glucose levels [10].

While GLP-1 agonists also target brain areas involved in hunger regulation and appetite suppression, they activate different brain cell populations compared to those affected by AMYRs and CTRs analogs.

This distinction suggests that combining cagrilintide with GLP-1 receptor agonists, such as semaglutide, may produce complementary effects.

Novo Nordisk is therefore investigating the combination of cagrilintide and semaglutide under the brand name CagriSema in two phase 3 clinical programs – namely the REIMAGE investigates its potential in T2D, while REDEFINE investigates its weight loss potential in different populations [11, 12].

Previous phase 1 and phase 2 trials have also indicated that these peptides work synergistically to reduce appetite and enhance glycemic control, presenting a promising approach for managing metabolic disorders [13].

Cagrilintide vs. Tirzepatide | Comparing Benefits and Research Applications

Although cagrilintide and tirzepatide differ in their mechanisms and structures, they share similar purposes, including enhancing blood sugar control and promoting weight loss.

As of now, cagrilintide has not received regulatory approval for medical use. However, it is currently being studied in phase 3 clinical trials alongside semaglutide.

Early research indicates that a combination of cagrilintide and semaglutide might be comparable to tirzepatide in terms of metabolic benefits.

The following sections offer a detailed comparison of the distinct features of these two peptides.

Cagrilintide vs. Tirzepatide for Weight Loss Research?

The ongoing phase 3 clinical program, REDEFINE, includes six trials, one of which is the REDEFINE-4 study [11].

This active trial is designed to compare the weight loss effects of tirzepatide versus the combination of cagrilintide and semaglutide over 72 weeks in 800 patients [14].

The initial results are anticipated in 2025. However, as of 2024, no data is available from this or other studies directly comparing cagrilintide with tirzepatide.

Existing clinical data, however, highlights the positive effects of both peptides. Noteworthy findings include:

• The SURMOUNT program, which led to FDA approval of tirzepatide, provides the most extensive research on its weight loss potential. The largest trial, SURMOUNT-1, reported an average weight reduction of 20.9% (approximately -45lb) from a baseline of 233lb over 72 weeks [15]. Additionally, an 88-week trial, SURMOUNT-4, demonstrated a mean weight loss of -25.4% from baseline [16].
• In a phase 1b trial, a combination of 2.4mg/weekly cagrilintide and semaglutide resulted in a 17.1% reduction in baseline body weight after just 20 weeks [17]. Another phase 2 trial, administering 4.5mg/week of cagrilintide alone, achieved a -10.8% (-25.4lb) mean weight reduction in 26 weeks [18].

Based on current data, tirzepatide seems to be more effective than cagrilintide alone or in combination with a GLP-1 agonist.

However, the relatively short duration of existing cagrilintide studies compared to the SURMOUNT trials means that the results of the ongoing longer phase 3 trials could provide new insights into this comparison.

Cagrilintide vs. Tirzepatide for Type 2 Diabetes Research?

The REIMAGINE clinical program, similar to the REDEFINE-4 study, includes the REIMAGINE-4 trial, which is designed to compare the weight loss potential and anti-diabetic effectiveness of tirzepatide against the combination of cagrilintide and semaglutide in patients with type 2 diabetes (T2D).

This 68-week, head-to-head trial plans to enroll 1,000 participants and will evaluate changes in baseline weight, fasting blood sugar levels, and glycated hemoglobin (HbA1c) levels, the latter being a crucial marker for long-term glycemic control in T2D [19].

Participant recruitment began in 2024, with initial results anticipated in 2026. In the meantime, researchers rely on existing data from previous phase 2 and phase 3 trials to assess how tirzepatide compares to cagrilintide in terms of glycemic control:

• Data from the SURPASS program shows that tirzepatide significantly improves glycemic control in T2D, reducing HbA1c by an average of 2.3%-2.4% from baseline, with reductions reaching up to 2.58% in some studies lasting 40-52 weeks [20, 21, 22, 23].

• In contrast, a smaller 32-week phase 2 trial with 92 participants found that HbA1c levels decreased by 2.2% with cagrilintide plus semaglutide, compared to 1.8% with semaglutide alone, and 0.9% with cagrilintide alone [24].

Overall, cagrilintide appears less effective than GLP-1 agonists or dual agonists like tirzepatide in improving glycemic control in T2D.

However, it may significantly enhance the efficacy of GLP-1 agonists, and ongoing phase 3 trials will determine whether this combination can outperform tirzepatide.

Cagrilintide and Tirzepatide | Dosage Comparison | Research Only

Cagrilintide and tirzepatide have long half-lives, enabling them to be administered once weekly. The following are example dosing schedules referenced from existing scientific literature. These dosing guidelines are intended for research purposes only.

Tirzepatide Dose for Weight Loss

The data from the SURPASS and SURMOUNT trials concerning tirzepatide's weight loss effects can be a valuable reference for weight loss research [15].

To minimize side effects, it is advisable to start with a low dose of 2.5mg/weekly, gradually increasing by 2.5mg every four weeks [25].

The following tirzepatide administration protocol aligns with these recommendations:

• Tirzepatide Dose: Researchers typically start with 2.5mg/weekly for the first four weeks, then increase to 5mg/weekly for weeks 5-8, 7.5mg/weekly for weeks 9-12, and 10mg/weekly for weeks 13-16. Consider further increasing to 12.5mg/weekly for weeks 17-20, and to 15mg/weekly for weeks 21 and beyond, depending on the subjects' responses.
• Frequency: Researchers have administered tripeptide subcutaneously injections once weekly.
• Study Duration: Previous studies using this regimen have lasted between 24 and 88 weeks.
• Notes: Researchers must not exceed a weekly dose of 15mg tirzepatide.

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 Dose for Weight Loss

In published research, the highest safe weekly dose of cagrilintide has been identified as 4.5 mg. The largest cagrilintide trial to date reached this dose within 16 weeks, starting at an initial dose of 0.3 mg per week [18].

Findings from other studies indicate comparable efficacy at weekly doses of 2.4 mg and 4.5 mg, particularly when combined with semaglutide. Consequently, ongoing phase 3 trials are initiating cagrilintide at 0.25 mg per week—similar to semaglutide's dosing protocol—and gradually increasing the dose to 2.4 mg per week by week 16 [11].

To minimize the risk of side effects, treatment always begins with a lower dose. Below is an example of a dosing regimen based on current data:

• Cagrilintide Dosing Protocol: Researchers typically start with 0.25 mg per week (Weeks 1-4), then increase to 0.5 mg per week (Weeks 5-8), 1 mg per week (Weeks 9-12), and 1.7 mg per week (Weeks 13-16), reaching a maintenance dose of 2.4 mg per week (Week 17+). Based on phase 2 trials, there is an optional increase to 4.5 mg per week (Week 21+).
• Administration: Subcutaneous injection, once weekly, usually in the abdomen.
• Study Duration: 32 weeks at 2.4 mg per week, 26 weeks at 4.5 mg per week; phase 3 trials are designed to last up to 72 weeks at 2.4 mg per week.
• Important: Do not exceed 4.5 mg per week. Rotate injection sites to reduce the risk of local side effects.

Cagrilintide and Tirzepatide | Side Effects and Safety

Although cagrilintide and tirzepatide target different receptors, they exhibit similar side effects and safety concerns, mainly due to their impact on slowing motility and causing gastrointestinal (GI) issues, with occasional gallbladder complications.

However, tirzepatide has been much more extensively studied than cagrilintide. Numerous phase 3 trials provide a detailed understanding of tirzepatide’s safety and side effect profile [25].

For example, a comprehensive meta-analysis of ten trials, including nearly 7,000 participants, revealed that adverse GI events were dose-dependent, affecting 39%, 46%, and 49% of individuals at 5mg, 10mg, and 15mg weekly doses, respectively [26].

The most frequently reported GI side effects at the 15mg weekly dose were:

• Nausea: 24%
• Diarrhea: 21%
• Belching: 16%
• Abdominal distension: 16%
• Abdominal discomfort: 15%
• Vomiting: 14%
• Constipation: 9%
• Dyspepsia: 9%
• Abdominal pain: 8%
• Elevated lipase: 7%
• Allergic reactions 3%

The discontinuation rate was highest at the 15mg weekly dose, ranging from 8% to 13% across different studies. Allergic reactions were generally mild to moderate. Serious side effects, including cholelithiasis, cholecystitis, and pancreatitis, were rare, affecting less than 1% [26].

In contrast, cagrilintide safety data primarily comes from small studies, the most significant being a phase 2 trial involving 706 participants, of which 101 received cagrilintide at a dose of 4.5 mg weekly for 26 weeks [18].

Reported side effects in this group included:

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

Approximately 88% of this subgroup experienced side effects, with 63% reporting gastrointestinal issues. One serious adverse event potentially linked to cagrilintide was acute cholelithiasis (gallstones). The overall discontinuation rate due to side effects was around 10% [18].

Where to Buy Cagrilintide Online | 2024 Edition

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Cagrilintide vs. Tirzepatide | Verdict

Preliminary and indirect data suggest that tirzepatide may have an advantage over cagrilintide, even when cagrilintide is combined with a GLP-1 agonist. Additionally, both peptides seem to share similar pharmacokinetics, side effects, and safety profiles.

However, upcoming phase 3 trials involving cagrilintide are expected to provide more definitive insights, including a direct comparison between tirzepatide and the cagrilintide + semaglutide combination (CagriSema).

Researchers seeking reference materials for either peptide can obtain them from our most reliable suppliers.