Mazdutide | Benefits and Research Applications

Researchers may find the emerging data on mazdutide of significant interest, particularly regarding its potential applications in weight management and metabolic disorders.

This innovative peptide has attracted attention due to its promising role in treating conditions such as:

• Overweight and obesity
• Type 2 diabetes (T2D)
• Metabolic dysfunction-associated steatohepatitis (MASH)

Recently, three phase 3 trials have been completed, and mazdutide has been approved for chronic weight management in China. Two more phase 3 trials are currently in progress.

Considering the fast development of the research involving this peptide, staying updated on the latest findings is essential to optimize future research outcomes.

Below, we summarize the current data on mazdutide's potential research applications and benefits. Additionally, we offer guidance on sourcing this peptide for laboratory research purposes.

What is Mazdutide | Overview

Mazdutide, also known as IBI362 or LY3305677, is a synthetic peptide analog of the hormone oxyntomodulin (OXM) [1]. Originally developed by Eli Lilly, its rights were acquired in 2019 by Innovent Biologics, a Chinese biotechnology company [2].

OXM, naturally produced in the gut, activates both glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors, which mazdutide also targets [3, 4].

However, mazdutide is modified with a fatty acid attachment, extending its half-life to at least 7.3 (up to 44.8 days in some patients), allowing for once-weekly dosing [5].

Mazdutide’s activation of GLP-1 receptors in various organs leads to several beneficial effects [6, 7]:

• Stimulates the release of insulin from the pancreas and normalizes elevated blood sugar levels
• Delays stomach emptying, enhancing fullness after a meal
• Activates brain cells in areas that regulate appetite, thus suppressing hunger and the release of hunger-promoting mediators – neuropeptide Y and agouti-related peptide.

On the other hand, GCG is a hormone known for raising blood sugar levels by stimulating glucose production in the liver. Yet GCG receptor activation primarily boosts energy expenditure [8]:

• The activation of GCG receptors in the liver increases fat breakdown and directly raises the body’s metabolic rates.
• In fatty tissue, GCG receptor activation encourages the transformation of white fat into a type of fat called beige fat. Unlike white fat, which stores energy, beige fat behaves more like brown fat, which makes the body use more energy to generate heat.

These dual actions—suppressing appetite and boosting metabolism—make mazdutide a promising candidate for treating obesity and type 2 diabetes (T2D).

It is currently undergoing extensive clinical trials in China under two major phase 3 programs: GLORY and DREAMS. The GLORY program focuses on weight loss, with one trial completed and another ongoing. The DREAMS program is investigating its potential in T2D management, with two trials already completed, while the third is ongoing [9].

Following these studies, mazdutide has been accepted for chronic weight management in adults with obesity or overweight by China's National Medical Products Administration (NMPA) [10].

However, it has not yet been approved by the U.S. Food and Drug Administration (FDA) and remains available only for research purposes to explore its potential further.

Research Applications and Benefits of Mazdutide | A Comprehensive Review

Researchers are actively investigating the potential of mazdutide in T2D, obesity and other metabolic diseases.

Currently, several ongoing phase 3 trials are already completed which show significant advantages of madutide over GLP-1 agonists.

Mazdutide for Glycemic Control and Weight Loss in Type 2 Diabetes

Researchers have explored the anti-diabetic potential of mazdutide, focusing on its ability to activate GLP-1 receptors. This peptide has been evaluated in phase 1b, phase 2, and phase 3 clinical trials for patients with type 2 diabetes (T2D), with one phase 3 trial still in progress.

The primary measures for assessing T2D management included changes in baseline glycated hemoglobin (HbA1c) levels, which indicate average blood glucose over the previous 3-4 months (typically over 6.5% in T2D), as well as changes in fasting blood sugar, body weight, blood pressure, lipid levels and more.

For example, a significant phase 2 trial with 250 T2D patients, compared 3mg, 4.5mg, or 6mg/weekly mazdutide against a daily 1.5mg dose of the FDA-approved GLP-1 agonist dulaglutide, or a placebo, over 20 weeks [11]. Key findings include:

• Mazdutide significantly lowered HbA1c levels, with the 4.5mg/weekly dose showing a reduction of -1.67%, compared to -1.35% with dulaglutide and no change with the placebo.
• Moreover, the 6mg/weekly dose led to a 7.11% weight loss from baseline, compared to a 2.69% reduction with dulaglutide and 1.38% with the placebo.
• By the 20th week, a greater proportion of participants taking mazdutide achieved HbA1c targets of <7.0% and ≤6.5% compared to dulaglutide or placebo.

Even more notably, the phase 3 DREAMS program includes three trials assessing mazdutide in T2D, with the first two trials completed but not yet published in a scientific journal.

According to a preliminary press release, the DREAMS-1 trial (NCT05628311) involved 320 T2D participants randomly assigned to receive 4mg/weekly or 6mg/weekly mazdutide, or a placebo, for 24 weeks.

After 24 weeks, those on placebo switched to 6mg/weekly mazdutide for an additional 24 weeks. The researchers reported the following [12]:

• The baseline characteristics of participants included an average HbA1c of 8.24% and an average body weight of 171.3 pounds.
• By week 24, reductions in HbA1c were -1.57% (4mg/weekly) and -2.15% (6mg/weekly) with mazdutide, compared to a 0.14% increase with the placebo.
• By week 48, participants receiving 6mg/weekly mazdutide showed a 9.6% weight loss from baseline.

The DREAMS-2 trial (NCT05606913) is a 28-week study involving 731 T2D patients, which has also been completed.

A preliminary press release suggests that mazdutide (4mg/weekly and 6mg/weekly) outperformed dulaglutide in lowering HbA1c, promoting weight loss, reducing blood pressure, improving blood lipid profiles, reducing hyperuricemia, and improving liver enzyme levels [13].

The ongoing DREAMS-3 study (NCT06184568) will compare the effectiveness of mazdutide vs another, more potent GLP-1 agonist called semaglutide, and it is expected to be completed in 2025 [14].

Mazdutide for Weight Loss in Non-Diabetics

Several phase 1 and 2 trials have investigated the potential of mazdutide for weight loss in non-diabetic individuals [15, 16, 17].

In comparison to its weight loss effectiveness in type 2 diabetes (mean reduction of -3.55%), studies show that mazdutide produces even more significant weight loss in non-diabetic participants (mean reduction of -8.44%) [18].

For example, a phase 2 study evaluated a higher dose of mazdutide—9mg/weekly—against a placebo over 24 weeks [19].

• The baseline characteristics of the 80 overweight or obese participants were as follows: weight: 213.6 lb, height: 168 cm, and BMI: 34.3.
• The mazdutide group saw a 15.4% greater reduction in mean body weight compared to the placebo group, with an average weight loss of -32.4 lb.
• Notably, 81.7% of the mazdutide group achieved a weight loss of 5% or more, while none in the placebo group did.

In another, larger phase 2 trial involving 248 non-diabetic participants, subjects received either 3 mg, 4.5 mg, or 6 mg of mazdutide weekly, or a placebo, over 24 weeks. Researchers observed a -12.3% greater weight loss difference with 6 mg/weekly mazdutide compared to the placebo [20].

This trial also included a group that received up to 9 mg/weekly for 48 weeks. The researchers reported a -18.6% placebo-adjusted mean reduction in body weight [21].

Innovent Biologics has initiated the GLORY phase 3 clinical program to further explore mazdutide's effects on weight loss. The first study in this series, GLORY-1, has been completed.

The GLORY-1 study (NCT05607680) involved 610 participants with a BMI over 28, or a BMI over 24 with at least one weight-related comorbidity. The average baseline weight was 192.2 lb, with a maximum dosage of 6 mg/weekly. Key findings from this phase 3 trial include [22]:

• After 48 weeks, participants in the 6 mg/weekly mazdutide group experienced an average weight reduction of -14% (-26.9 lb) from baseline.
• Mazdutide significantly outperformed placebo in improving insulin sensitivity in participants with HbA1C levels between 5.7% and 6.5% (indicating prediabetes, aka insulin resistance syndrome).
• Mazdutide also led to significant reductions in waist, hip, and neck circumferences, suggesting a reduction in subcutaneous fat.

The upcoming GLORY-2 trial aims to enroll 450 subjects, who will be randomized to receive either 9 mg/weekly mazdutide or a placebo for 60 weeks, with weight loss as the primary endpoint.

Mazdutide for Visceral Obesity

Visceral obesity refers to the accumulation of fat around internal organs and the abdominal wall. This type of fat is highly metabolically active, contributing to the release of triglycerides and inflammatory molecules, which disrupt normal endocrine and metabolic function.

This condition is linked to various metabolic disorders, including insulin resistance, metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes (T2D), and an elevated risk of cardiovascular disease.

Clinical trials including phase 2 and phase 3 studies have demonstrated several benefits in addressing MASLD (also known as MASH), hypertension, hypercholesterolemia, hypertriglyceridemia, and other metabolic conditions.

For instance, a meta-analysis of seven phase 1 and phase 2 studies involving mazdutide, which spanned 12-24 weeks and included 680 participants with and without T2D, revealed the following significant findings [18]:

• The data indicated substantial reductions in cardiovascular risk factors compared to placebo across all tested doses, particularly between 3mg/week and 10mg/week.
• Notable reductions included systolic blood pressure (average decrease of -7.57mmHg), diastolic blood pressure (average decrease of -2.98mmHg), total cholesterol (average decrease of -16.82%), triglycerides (average decrease of -43.29%), and low-density lipoprotein (average decrease of -17.07%).

In the phase 3 GLORY-1 trial, a subset of participants underwent MRI scans and liver fat content (LFC) measurements using MRI-proton density fat fraction (MRI-PDFF). The most notable findings after 48 weeks of mazdutide therapy are as follows [23]:

• Among participants with MASH and a baseline LFC of 5% or more, and 10% or more, treatment with mazdutide at 4mg/week or 6mg/week for 48 weeks led to significant, dose-dependent reductions in LFC, outperforming placebo.
• Participants with a baseline LFC of 10% or higher experienced an average relative reduction of -80.2% with the 6mg/week dose.
• Mazdutide also showed superior effects compared to placebo in reducing systolic blood pressure, triglycerides, total cholesterol, LDL-C, blood uric acid, and liver enzymes from baseline.

Recommended dosage for Mazdutide

In research studies examining the effects of mazdutide on weight loss, the drug is administered according to specific protocols.

Researchers generally start with a dose of 2mg/week for the first four weeks. This gradual increase is intended to minimize potential side effects.

The dose is then gradually increased over at least nine weeks, typically by doubling it every four weeks for the first eight weeks, until a weekly dose of 6 mg is reached [22, 24].

In some studies, higher doses of 9 mg and 10mg/weekly have been reached through a faster dosing regimen.

However, it is generally recommended to follow the standard protocol of up to 6mg/weekly, with an increase to 9mg/weekly only if necessary after the first 12 weeks [16, 19].

Mazdutide is administered once weekly, and it can be taken at any time of day, with or without food. Dosages are carefully monitored to ensure they do not exceed 10mg/weekly. A typical dosing schedule observed in studies is as follows:

• Mazdutide Dosage: Researchers start at 2mg/weekly for the first four weeks, increase to 4mg/weekly during weeks 5-8, and then to 6mg/weekly from week 9 onward. In some cases, the dose is further increased to 9mg/weekly from week 13 onward, depending on the research objectives.
• Frequency: Once weekly, administered subcutaneously.
• Study Duration: Up to 48 weeks at 6mg/weekly, up to 24 weeks at 9mg/weekly, and up to 16 weeks at 10mg/weekly. Future phase-3 trials (GLORY-2) are planned to last up to 60 weeks at 9mg/weekly.
• Notes: The dosage should not exceed 10mg/weekly. If a dose is missed, it is typically administered within five days or skipped, with subsequent doses continuing according to the original schedule.

Where to buy Mazdutide online | 2024 Edition

Mazdutide can be legally sourced from specialized suppliers as a reference material.

Ensuring successful experimental outcomes requires researchers and lab professionals to choose only reliable peptide suppliers. After evaluating various vendors, our review team identified the following supplier that stands out for consistently meeting high standards in purity, prompt delivery, and customer support.

Polaris Peptides

Polaris Peptides is known for providing high-quality peptides specifically designed for professional research and development with several key benefits, including:

• Transparency: Detailed lab results accompany every Polaris peptide for sale, providing you with the assurance of mazdutide’s quality and integrity.
• Purity and Precision: Polaris mazdutide for sale is crafted with the utmost precision, ensuring a purity level of over 99%.
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• Special Offers:The supplier offers free shipping on orders over $350 and an additional 10% discount for those who subscribe to their marketing. Plus, spending $500 or more earns a complimentary vial from their ‘Other Peptides’ category.
  

 

Benefits of Mazdutide | Overall

Mazdutide is a new GLP-1/GCG agonist that offers distinct advantages in enhancing glycemic control and promoting weight loss, outperforming some earlier GLP-1 agonists. It has been approved in China for long-term weight management.

Ongoing research is exploring its potential benefits at higher doses for fat reduction, as well as its anti-diabetic and liver-protective effects in type 2 diabetes.

Researchers seeking high-purity mazdutide for experimental purposes can rely on our most trusted vendor and leading supplier in the research chemicals industry.