Mazdutide for Weight Loss | How Does It Work

Researchers seeking to explore mazdutide for weight loss will find valuable insights in this comprehensive science-based guide.
Mazdutide is already approved for medical use by regulatory agencies in China and phase 3 clinical trials are currently evaluating its effectiveness in key areas, including:

• Weight loss in individuals with obesity
• Weight management in diabetes
• Glycemic control

This guide highlights the latest research and peer-reviewed studies, focusing on mazdutide's mechanisms and benefits for weight management, along with essential considerations regarding side effects and dosage.

Lastly, expert advice is provided on obtaining high-quality mazdutide online for lab experimentation, enabling researchers to safely and effectively integrate this peptide into their studies.

What is Mazdutide | Overview

Mazdutide (also known as IBI362) belongs to a class of drugs called oxyntomodulin (OXM) analogs. Originally developed by Eli Lilly, the rights to this peptide were acquired in 2019 by the Chinese company Innovent Biologics [1].

The structure of mazdutide is based on the OXM peptide, with chemical modifications, including fatty acid side chains, applied to extend its half-life and optimize its therapeutic efficacy.

This results in a prolonged half-life that enables once-weekly subcutaneous injections, offering sustained therapeutic benefits [2].

OXM is a naturally occurring peptide that targets key receptors related to metabolism. Similarly, its analogs like mazdutide also target these receptors [3]:

• Glucagon-like peptide-1 receptors (GLP-1Rs) – depending on the target organ, their activation may promote insulin secretion, inhibit glucagon release, slow gastric emptying, and enhance satiety.
• Glucagon receptors (GCGRs) – depending on the target tissue, activation of these receptors promotes glycogen breakdown and affects energy expenditure and metabolism.

Mazdutide was developed to combine the effects of GLP-1 and glucagon receptor activation, providing a new therapeutic avenue for managing weight and metabolic disorders, such as type 2 diabetes (T2D).

While mazdutide is not yet approved by the U.S. Food and Drug Administration (FDA), several phase 3 trials are underway or already completed. These trials are part of two major phase 3 clinical programs [4]:

• The GLORY program includes two trials, one completed and one ongoing, that focus on its use in managing obesity.
• Meanwhile, the DREAMS program encompasses three trials, two completed and one ongoing, aimed at assessing mazdutide’s efficacy in managing type 2 diabetes (T2D).

Following promising results from these trials, the National Medical Products Administration (NMPA) of China has accepted mazdutide for the treatment of chronic weight management in adults with obesity or overweight [5].

Mazdutide is also available as a reference material for laboratory research.

Mazdutide Side Effects | Overview

As of 2024, researchers are yet to publish the detailed safety data from the completed phase 3 trials. Yet, the media announcements clearly state that the peptide continues to show a favorable safety profile, similar to those observed in phase 2 trials [6].

The most common side effects associated with OXM agonists like mazdutide include gastrointestinal issues and delayed gastric emptying, resulting in symptoms such as nausea and vomiting. These side effects are usually mild to moderate and can be mitigated by starting at a low dose that is gradually escalated.

A meta-analysis of all phase 1 and phase 2 studies on mazdutide (including 7 trials with 680 participants, both with and without T2D) has clearly demonstrated the most common side effects of mazdutide, and how they compared to placebo [7]:

• Nausea: Participants on mazdutide had a 4.22 times higher risk of nausea
• Vomiting: A similarly increased risk of vomiting was observed (4.91 times higher).
• Decreased Appetite: Those taking mazdutide also showed a 2.3-fold higher incidence of appetite reduction.
• Diarrhea: The occurrence of diarrhea varied between participants with and without T2D. Diabetic participants had a 3.84 times higher risk, while non-diabetics did not show a statistically significant increase in risk.
• Increased Heart Rate: Across all studies, mazdutide was associated with an increase in heart rate, with changes ranging from 5.0 to 17.4 beats per minute (bpm) compared to placebo (1.7 to 4.8 bpm). However, there was no increased risk of cardiac events associated with the elevated heart rate.

There were no serious side effects attributed to mazdutide therapy. Moreover, no statistically significant differences were observed for other adverse events such as hypoglycemia, urinary tract infections, dyspepsia, or upper respiratory tract infections when compared to placebo.

One of the largest phase 2 trials, which was performed in overweight and obese people without T2D reported the following incidence of side effects after 24 weeks of 6mg/weekly mazdutide therapy [8]:

• Diarrhea – 30.2% of 61 participants
• Nausea – 23.8%
• Vomiting – 20.6%
• Decreased appetite – 15.9%
• Abdominal distension – 11.1%
• Increased pancreatic enzyme levels – 1.6%

How Mazdutide Works for Weight Loss

As a synthetic analog of the naturally occurring gut peptide oxyntomodulin (OXM), mazdutide interacts with both GLP-1 and GCG receptors, addressing two crucial aspects of energy balance—appetite suppression and energy expenditure.

Here are the most important mechanisms related to mazdutide’s potential for GLP-1 receptor activation [9, 10]:

• In the Pancreas: Mazdutide stimulates insulin release, which helps normalize elevated blood sugar levels. This makes it beneficial for managing type 2 diabetes.
• In the Digestive System: Activation of GLP-1 receptors delays gastric emptying, leading to prolonged feelings of fullness and reduced food intake.
• In the Brain: GLP-1 receptors are also present in neurons that express proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Mazdutide's activation of these neurons induces feelings of satiety while suppressing the release of hunger-promoting mediators, such as neuropeptide Y (NPY) and agouti-related peptide (AgRP), which reduces appetite.

Below we also detail the most important mechanisms related to GCG receptor activation [11]:

• In the Liver: Activating GCG receptors stimulates the production of glucose and increases fat breakdown, directly raising metabolic rates and increasing energy expenditure.
• In Fat Tissue: Mazdutide promotes the transformation of white fat (which stores energy) into beige fat, a form that behaves more like brown fat, which burns energy to generate heat. This process helps boost overall energy expenditure, contributing to weight loss.

By engaging both the GLP-1 and GCG receptors, mazdutide addresses both sides of the energy equation—reducing calorie intake and increasing calorie burn—making it a promising treatment for weight loss and metabolic disorders like obesity and type 2 diabetes [3].

Benefits of Mazdutide for Weight Loss

The available phase 2 and phase 3 studies reveal the significant weight loss potential of mazdutide, which appears to be comparable or superior to that of FDA-approved GLP-1 agonists.

Below we have highlighted the weight loss effectiveness of the peptide as demonstrated in different population groups such as overweight and obese people with or without T2D. We also outline future research that will further elucidate the weight loss potential of mazdutide.

Mazdutide for Weight Loss in T2D

Mazdutide has been widely studied for its potential to improve glycemic control in overweight and obese individuals with T2D, with glycated hemoglobin (HbA1c) changes often used as the main measure of effectiveness.

Moreover, the most notable phase 2 trials and phase 3 trials have also reported on weight loss:

• In a phase 2 trial with 250 T2D patients, mazdutide was tested at 3mg, 4.5mg, and 6mg/weekly, compared to daily 1.5mg dulaglutide (FDA-approved daily GLP-1 agonist) or placebo. After 20 weeks, the 6mg/weekly mazdutide group saw a -7.11% weight loss from baseline, compared to -2.69% with dulaglutide and -1.38% with placebo. Mazdutide also decreases HbA1c by -1.67%, versus -1.35% for dulaglutide and no change for the placebo [12].
• The phase 3 DREAMS-1 trial involved 320 T2D participants with an average body weight of 171.3lb. Participants received up to 6mg/weekly mazdutide for a maximum of 48 weeks and achieved a mean -9.6% weight reduction which is -16.4lb. Moreover, HbA1c dropped by -2.15% from a baseline of 8.24% within the first 24 weeks [13].

The phase 3 DREAMS-2 trial, which is a 28-week study involving 731 T2D patients, has also been completed. Initial reports indicate that mazdutide (4mg/weekly and 6mg/weekly) has demonstrated superior outcomes to dulaglutide and placebo for weight loss and glycemic control, although detailed results have yet to be published [14].

Mazdutide for Weight Management in Non-Diabetics

Mazdutide has been widely studied in overweight and obese individuals without T2D. Notable trials in this group include one phase 2 study and the two phase 3 trials from the GLORY-1 program.

In the phase 2 study, 328 participants without T2D were split into two subgroups:

1. The first involved 248 participants who were randomly assigned to receive either 3mg, 4.5mg, or 6mg/weekly of mazdutide, or a placebo. After 24 weeks, weight loss was found to be dose-dependent. The group receiving 4.5mg/weekly lost 11.4% more weight than the placebo group, while those on 6mg/weekly lost 12.3% more [8].
2. The second subgroup included 80 participants who received up to 9mg of mazdutide weekly for 24 weeks, with an option to extend treatment for another 24 weeks. The initial 24-week results showed a 15.4% greater weight loss in the mazdutide group compared to placebo. The researchers are yet to reveal the 48-week results [15].

The GLORY-1 phase 3 trial involved 610 participants with a BMI over 28 or a BMI over 24 with at least one weight-related condition. The average starting weight was 192.2 lbs, and the highest dose administered was 6mg/week.

Here are the most notable results highlighted by the researchers [6]:

• After 48 weeks, participants in the 6mg/weekly group saw an average weight loss of 14% (-26.9 lbs) from baseline. The trial also reported reductions in waist, hip, and neck measurements, indicating fat loss.
• Mazdutide further improved insulin sensitivity in participants with HbA1C levels of 5.7% or higher (signaling prediabetes), and was significantly more effective than placebo.

Future Mazdutide Weight Loss Research

As of 2024, there are a couple of phase 3 trials that are still ongoing. Namely, these are the GLORY-2 and DREAMS-3 studies, both of which target overweight and obese individuals (with or without T2D), and weight loss is listed as one of their primary goals.

Here are more details about each of these studies [16]:

• The ongoing GLORY-2 phase 3 trial plans to enroll 450 participants, who will be randomized to receive a higher 9mg/weekly mazdutide. The study is planned to last for 60 weeks, during which it will compare the effectiveness of this higher dose to placebo.
• DREAMS-3 has not yet started as of 2024, and the specific parameters related to it such as dosages or duration are yet to be announced. However, this study will provide valuable information about the weight loss potential of mazdutide and compare it head-to-head vs another FDA-approved weight loss peptide called semaglutide.

Mazdutide Dosage for Weight Loss

Mazdutide is administered as a once-weekly injection due to its long half-life, allowing flexibility in timing as long as it's the same day each week, regardless of meals or other factors.

Dosing typically begins at lower levels and gradually increases to reduce the risk of side effects. Most phase 3 trials follow a similar pattern, starting at 2mg/weekly and increasing over eight weeks to 6mg/weekly [6, 17].

The GLORY-2 phase 3 trial is exploring doses up to 9mg/week, as phase 2 studies indicated this dose is safe and possibly more effective [15, 18]. However, since the dosing schedule for GLORY-2 hasn’t been published, it’s uncertain whether the escalation to 9mg will occur in 8 weeks or follow a slower approach.

A more gradual plan could involve a 12-week escalation to reach 9mg/week, such as the following:

• Mazdutide Dosage: Phase 3 trials typically start with 2mg/weekly for four weeks, increasing to 4mg/weekly in weeks 5-8, then to 6mg/weekly from week 9 onward. A further increase to 9mg/weekly from week 13 is possible, depending on study objectives.
• Frequency: Administered weekly via subcutaneous injection.
• Study Duration: Up to 48 weeks at 6mg/week, with GLORY-2 expected to extend up to 60 weeks at 9mg/week.
• Notes: Researchers should not exceed 10mg/weekly.

Where to buy Mazdutide online | 2024 Edition

Researchers can legally obtain mazdutide from specialized vendors as a reference substance.
For successful experimental results, it’s essential for researchers and laboratory professionals to select reputable peptide suppliers. After assessing multiple providers, our team found the following vendor excels in product purity, timely delivery, and excellent customer service.

Polaris Peptides

Polaris Peptides offers high-grade peptides designed specifically for research and development, with the following advantages:

• Full Transparency: Each Polaris peptide comes with detailed lab reports, ensuring the quality and integrity of mazdutide.
• High Purity and Accuracy: Polaris mazdutide is produced with high precision, maintaining a purity level exceeding 99%.
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• Special Discounts: The vendor offers free shipping for orders above $350, along with a 10% discount for newsletter subscribers. Additionally, purchases over $500 include a complimentary vial from their ‘Other Peptides’ selection.