Mazdutide | A Comprehensive Peptide Overview

Researchers may be looking for a comprehensive review of mazdutide peptide overview as it is a novel peptide that has only recently been studied in depth.

In particular, this peptide has undergone several phase 3 trials, showing significant promise for treating type 2 diabetes (T2D) and promoting weight loss. Additional potential benefits are also under investigation.

Currently, scientists have several avenues to explore in studying mazdutide, such as:

• Chronic weight management in cases of overweight and obesity
• Enhancing glycemic control in T2D
• Addressing other metabolic conditions, such as non-alcoholic fatty liver

To fully harness the research potential of mazdutide, researchers need to stay informed about the latest developments.

Therefore, this guide is designed to provide valuable insights into mazdutide research, offering an overview of its structure and mechanisms, information on potential research applications, and details on the most recent trials.

We also provide advice on sourcing research-grade mazdutide.

What is Mazdutide

Mazdutide, also known by its scientific designations IBI362 or LY3305677, is a promising peptide initially developed by the American pharmaceutical company Eli Lilly and is now studied by Innovent Biologics [1].

In 2019, Innovent Biologics, a leading China-based biotechnology company, secured the rights to mazdutide from Eli Lilly, marking a significant collaboration in the pharmaceutical industry.

Mazdutide is a synthetic peptide analog of the naturally occurring hormone oxyntomodulin (OXM) [2].

Here is what researchers should know about this hormone [3]:

• OXM is a 37 amino acid peptide hormone produced in the gut, primarily in the L-cells of the small intestine, following food intake. It contains the complete amino acid sequence of glucagon (GCG) but with the addition of eight amino acids on the C-terminal.
• This hormone plays a critical role in regulating various physiological processes, including appetite suppression, glucose metabolism, and energy expenditure.
• It achieves these effects by activating two key receptors in the body: the glucagon-like peptide-1 (GLP-1) receptor and the GCG receptor.

Similarly, mazdutide, as an analog of oxyntomodulin, mimics the hormone’s activity by activating the GLP-1 and GCG receptors. This dual activation is crucial for its research potential, which includes lowering blood sugar levels and reducing appetite.

Further, mazdutide is subjected to several molecular modifications, which extend its half-life up to several days and allow for once-weekly administration. These properties make mazdutide a promising candidate for treating conditions like obesity and type 2 diabetes.

Mazdutide is currently the focus of extensive clinical research, particularly in China, under two major phase 3 clinical programs called GLORY and DREAMS [4].

The GLORY program investigates the weight-loss potential of the peptide:

• GLORY-1: A completed 48-week phase 3 study conducted on Chinese adults who were overweight or obese.
• GLORY-2: An ongoing 60-week phase 3 study conducted in Chinese adults with obesity, involving 9mg/weekly mazdutide.

The DREAMS program investigates the potential of the peptide in T2D management:

• DREAMS-1: A completed 48-week phase 3 study focused on newly treated Chinese patients with type 2 diabetes.
• DREAMS-2: A completed 28-week phase 3 study comparing the efficacy of mazdutide with dulaglutide in Chinese patients with type 2 diabetes.
• DREAMS-3: An ongoing phase 3 study comparing mazdutide with semaglutide in Chinese patients with type 2 diabetes and obesity.

Following the completion of several of these studies, mazdutide has been accepted for chronic weight management in adults with obesity or overweight by the Centre for Drug Evaluation of the National Medical Products Administration (NMPA) of China [5].

However, it is important to note that, as of now, mazdutide has not yet been approved by the U.S. Food and Drug Administration (FDA). It remains available to researchers as a reference material, allowing continued exploration of its potential therapeutic benefits.

Mazdutide | Breakthrough in Obesity Research

As mentioned, mazdutide is a synthetic analog of the naturally occurring gut peptide OXM. Mazdutide and OXM both work by interacting with the receptors for the GLP-1 hormone, and the GCG hormone.

Studies suggest that activating the GLP-1 receptors can suppress appetite and reduce the intake of energy (calories) with food while activating the GCG receptors stimulates metabolic processes that lead to higher energy expenditure [6].

Therefore, mazdutide may aid weight loss by interacting with both sides of the energy balance that ultimately determines body weight. Here are more details on how exactly activating these receptors may contribute to appetite suppression and faster metabolism:

• Mazdutide activates the GLP-1 receptors in the pancreas, which stimulates the release of insulin and normalizes elevated blood sugar levels. These receptors are also found in the digestive system, and activating them delays stomach emptying, enhancing fullness after a meal.
• Moreover, GLP-1 receptors are found in the brain, particularly on neurons that express the so-called proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). Activating them induces satiety and indirectly suppresses the release of hunger-promoting mediators – neuropeptide Y (NPY) and agouti-related peptide (AgRP).
  [7, 8].
• The GCG receptor is mainly known for raising blood sugar levels by stimulating glucose production in the liver. However, by activating it, mazdutide appears to upregulate energy expenditure. This may be due to the activation of GCG receptors in the liver and the fatty tissue. In the liver that increases fat breakdown and directly raises the body’s metabolic rates.
• Additionally, 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 [9].

Mazdutide | Range of Potential Benefits

Mazdutide is under active research in phase 3 trials regarding its potential for weight loss and chronic weight management in obesity.

Further, the activation of the GLP-1 receptors gives mazdutide a significant potential for lowering blood sugar levels and improving glycemic control in T2D, while the GCG receptor activation helps reduce liver fat in conditions like non-alcoholic fatty liver disease (NAFLD).

Below, we have highlighted the latest evidence on the peptide and its research potential.

Weight Management and Obesity Research

Multiple phase 1 and phase 2 trials have explored the weight loss potential of mazdutide [10, 11, 12].

Here are some of the key findings:

• In a phase 2 trial involving 248 participants, subjects were randomized to receive either mazdutide at doses of 3mg, 4.5mg, or 6mg/week, or a placebo.
• The results showed that the mean percentage change in body weight from baseline to week 24 ranged from -6.7% to -11.3% for the mazdutide groups, compared to a +1% change with placebo. The highest dose of 6mg/weekly demonstrated a treatment difference of up to -12.3% compared to placebo [13].
• Another phase 2 study assessed a higher dose of mazdutide in 80 Chinese participants with obesity (average baseline weight: 213.6lb, height: 168cm, BMI: 34.3). Participants were randomized in a 3:1 ratio to receive either 9mg/weekly mazdutide or a placebo for 24 weeks.
• The mazdutide group exhibited a -15.4% greater reduction in mean body weight compared to the placebo group, with an average weight loss of -32.4lb. Notably, 81.7% of participants in the mazdutide group achieved a weight loss of 5% or more, whereas none in the placebo group reached this threshold [14].

nnovent Biologics has also launched the GLORY phase 3 clinical program to further investigate mazdutide’s weight loss effects. The first study in this program, GLORY-1, has been completed.

The GLORY-1 study included 610 participants with a BMI greater than 28, or a BMI over 24 with at least one weight-related comorbidity. The average baseline weight was 192.2lb, with the maximum dosage set at 6mg/weekly. Key findings from this phase 3 trial include [15]:

• After 48 weeks, participants in the 6mg/weekly mazdutide group experienced an average weight reduction of -14% (-26.9lb) from baseline.
• Mazdutide also led to significant reductions in waist, hip, and neck circumferences, suggesting its effectiveness in reducing body fat.
• Additionally, for participants with HbA1C levels of 5.7% or higher, mazdutide significantly outperformed placebo in improving insulin resistance.

Blood Glucose Control in T2D

Mazdutide stimulates GLP-1 receptors in the pancreas in a glucose-dependent manner, promoting insulin release and normalizing blood sugar levels.

Subsequent phase 1b, 2, and 3 studies have explored the peptide's potential to enhance glycemic control in patients with type 2 diabetes (T2D) and its safety profile [16].

A key metric for evaluating effectiveness is glycated hemoglobin (HbA1c) levels, reflecting average glucose over the past 3-4 months. Below are some significant studies on mazdutide's impact on T2D:

• A phase 2 trial involving 250 T2D patients examined mazdutide at doses of 3mg, 4.5mg, or 6mg/weekly, compared to 1.5mg/daily dulaglutide or placebo over 20 weeks. Mazdutide significantly reduced HbA1c levels, up to -1.67% with the 4.5mg/weekly dose, compared to -1.35% with dulaglutide and no change with placebo.
• Additionally, the 6mg/weekly dose resulted in a -7.11% weight loss from baseline, versus -2.69% with dulaglutide and -1.38% with placebo. By week 20, more mazdutide participants reached the HbA1c targets of <7.0% and ≤6.5% compared to those on placebo and dulaglutide [17].
• The phase 3 DREAMS-1 trial (NCT05628311) included 320 T2D participants with an average HbA1c of 8.24% and a mean body weight of 171.3lb. Participants were randomly assigned to receive either 4mg/weekly or 6mg/weekly mazdutide, or a placebo, for 24 weeks. After this period, those on the placebo also switched to 6mg/weekly mazdutide for another 24 weeks.
• At week 24, HbA1c reductions were -1.57% (4mg/weekly) and -2.15% (6mg/weekly) with mazdutide, compared to a +0.14% increase with placebo. By week 48, the 6mg/weekly mazdutide group showed a -9.6% weight loss from baseline [18].
• The phase 3 DREAMS-2 trial (NCT05606913) has also concluded, though its results have yet to be published in a scientific journal. This 28-week study, involving 731 T2D patients, compared 4mg/weekly and 6mg/weekly mazdutide against 1.5mg/daily dulaglutide.

The findings indicate that mazdutide was more effective than dulaglutide in lowering HbA1c, achieving greater weight loss, and improving blood pressure, blood lipids, serum uric acid, and liver enzymes [19].

Other Metabolic Benefits

Preclinical and clinical research indicates that mazdutide may offer benefits for metabolic conditions beyond obesity and type 2 diabetes.

For instance, one preclinical study suggests that this peptide could reduce uric acid levels in hyperuricemia to a degree comparable to that of anti-gout medications [20].

Additionally, phase 1b, phase 2, and phase 3 clinical trials have highlighted several benefits concerning cardiovascular risk factors and liver conditions such as metabolic-associated fatty liver disease (MAFLD). Here are some key findings:

• A meta-analysis of all phase 1 and phase 2 studies on mazdutide (including 7 trials with 680 participants, both with and without T2D) showed significant reductions in systolic blood pressure (mean decrease of -7.57mmHg), diastolic blood pressure (mean decrease of -2.98mmHg), total cholesterol (mean decrease of -16.82%), triglycerides (mean decrease of -43.29%), and low-density lipoprotein (mean decrease of -17.07%) compared to placebo.
• Weight loss was more substantial in non-diabetic participants (mean reduction of -8.44%) than in those with diabetes (mean reduction of -3.55%) [21].
• The GLORY-1 trial also involved a subset of participants who underwent MRI scans and liver fat content (LFC) measurement using MRI-proton density fat fraction (MRI-PDFF). In participants with baseline LFC of 5% or more and 10% or more, treatment with mazdutide at 4mg/weekly or 6mg/weekly for 48 weeks resulted in significant and dose-dependent reductions in LFC, surpassing the effects seen with placebo.
• Notably, participants with a baseline LFC of 10% or more experienced an average relative reduction of -80.2% with the 6mg/weekly dose. Mazdutide also outperformed placebo in lowering systolic blood pressure, triglycerides, total cholesterol, LDL-C, blood uric acid, and liver enzymes compared to baseline [22].

Where to buy Mazdutide online | 2024 Edition

Mazdutie is accessible as a reference material through specialized suppliers.
It is essential for skilled researchers and laboratory professionals to select a trustworthy peptide provider to enhance the probability of successful experimental results.

After purchasing mazdutide from various vendors, our peptide review team found that the following supplier consistently excels in maintaining high standards for purity, prompt delivery, and customer support.

Polaris Peptides

As a newer supplier in the market, Polaris Peptides provides high-quality peptides specifically tailored for research and development by professionals. This vendor offers several notable 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%.
• Customer Support:Polaris Peptides is committed to providing fast shipping and personalized support, ensuring a seamless purchasing experience
• 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.