▎Maz Research
What is the research background of Maz?
The prominent issue of global obesity and related diseases:
Overweight and obesity have become increasingly severe global public health challenges. According to the World Obesity Atlas, the number of obese people globally reached 764 million in 2020 and is expected to rise to 1 billion by 2030. Obesity can trigger numerous health complications, such as cardiovascular diseases and type 2 metabolism, which seriously affect the individual's quality of life and global medical resources. This has driven researchers to explore effective treatment methods, especially new drugs.
The development foundation of incretin-based drugs:
Since the concept of incretin was proposed in 1932, related research has been steadily advancing. In 1987, GLP-1 was identified as a key regulator of insulin secretion in the pancreas, and treatment regimens for type 2 metabolism based on incretin were developed. In 2005, exenatide, the world's first GLP-1 receptor agonist (GLP-1RA), was approved for marketing, laying a solid theoretical and practical foundation for the research and development of new incretin-based drugs like Maz. Maz is an analog of mammalian oxyntomodulin (OXM). As a new-generation dual agonist targeting GLP-1R and GCGR, it has a unique dual-action mechanism and broad prospects in the treatment of weight loss and related diseases.
What is the mechanism of action of Maz?
Agonistic effect on the glucagon-like peptide-1 (GLP-1) receptor:
GLP-1 is an intestinal hormone that can promote insulin secretion and inhibit glucagon secretion in a glucose concentration-dependent manner, thereby reducing blood glucose levels [1]. As a GLP-1 receptor agonist, Maz mimics the action of GLP-1, enhancing insulin secretion and reducing glucagon release, which helps regulate blood glucose. Moreover, GLP-1 receptor agonists can delay gastric emptying, enhance satiety, and reduce food intake, which is beneficial for weight control [1, 2].
Agonistic effect on the glucagon receptor:
Glucagon can promote the breakdown of liver glycogen and gluconeogenesis, leading to an increase in blood glucose. Maz, by activating the glucagon receptor, can regulate multiple aspects of glucose metabolism, achieving fine regulation of blood glucose. Glucagon also promotes lipolysis, helping to reduce fat accumulation and lower body weight [1, 2].
Regulatory effect on blood pressure:
Maz can reduce both systolic and diastolic blood pressure. On the one hand, it lowers blood pressure by regulating glucose and lipid metabolism and improving vascular endothelial function; on the other hand, it may affect blood pressure regulation mechanisms such as the renin-angiotensin system.
What is the specific mechanism of Maz for weight loss?
Regulation of blood glucose and metabolism:
As a dual agonist of the glucagon-like peptide-1 (GLP-1) and glucagon receptors, one of the multiple physiological effects of GLP-1 is to regulate blood glucose levels. It promotes insulin secretion, inhibits glucagon secretion, reduces blood glucose[1], delays gastric emptying, increases satiety, and reduces food intake. Glucagon, on the other hand, promotes lipolysis and energy consumption. Therefore, Maz activates both receptors and regulates blood glucose metabolism to achieve weight loss. Studies have shown that Maz can reduce body weight, blood pressure (systolic and diastolic), total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein levels[3], indicating that it can lead to weight loss and improve obesity-related metabolic disorders.
Influence on appetite and energy intake:
Maz may achieve weight loss by influencing appetite and energy intake. In some clinical trials, participants experienced gastrointestinal reactions such as decreased appetite after using Maz[3]. This may be caused by the direct action of Maz on the gastrointestinal tract or through regulation by the central nervous system. Regardless of the mechanism, decreased appetite and gastrointestinal side effects will reduce energy intake and promote weight loss. In addition, Maz may affect appetite by regulating neurotransmitters and hormones in the brain. For example, GLP-1 can act on the hypothalamus to regulate appetite and energy balance[4].
What are the specific action pathways of Maz in regulating blood glucose?
Stimulation of insulin secretion:
Glucagon-like peptide-1 (GLP-1) receptor agonists can stimulate insulin secretion. As a dual agonist of GLP-1 and glucagon receptors, Maz may activate the GLP-1 receptor to prompt pancreatic islet β cells to secrete insulin. Insulin is a key hormone for reducing blood glucose, which can promote cells to take up glucose and lower blood glucose levels[1].
Inhibition of glucagon secretion:
At the same time, Maz may act on the glucagon receptor to inhibit glucagon secretion. Glucagon and insulin are antagonistic to each other in blood glucose regulation, and reducing its secretion is conducive to lowering blood glucose[1].
Regulation of glucose metabolism:
Maz may regulate glucose metabolism at multiple levels to exert its hypoglycemic effect, such as affecting the glucose metabolism in the liver, muscle, and adipose tissues. In the liver, it reduces the breakdown of liver glycogen and gluconeogenesis, decreasing the production of blood glucose; in muscle tissue, it promotes the uptake and utilization of glucose; in adipose tissue, it regulates lipid metabolism, reduces the release of free fatty acids, and indirectly affects blood glucose[1, 3].
Influence on appetite and energy intake:
Studies have found that Maz can reduce appetite and energy intake, possibly by acting on receptors in the central nervous system and regulating the appetite signaling pathway. Reducing food intake can lower the source of blood glucose and help control blood glucose levels[3, 5].
![2]( "2")
Change from baseline in body weight and waist circumference.
a.Percent change from baseline in bodyweight over time. b. Change from baseline in bodyweight over time.
Source:PubMed[2]
What are the applications of Maz?
Treatment of type 2 metabolism:
A randomized, double-blind, placebo-controlled Phase 2 trial showed that Maz, a weekly-administered dual agonist of glucagon-like peptide 1 (GLP-1) and glucagon receptors, demonstrated good efficacy and safety in Chinese patients with type 2 metabolism[1].
Application in weight loss:
Research on patients with and without metabolism: A systematic review and meta-analysis showed that Maz can effectively reduce the body weight of adults with or without metabolism[3]. The research included seven randomized controlled trials with a total of 680 participants. The results showed that compared with the placebo, Maz led to a more significant reduction in body weight (mean difference [MD] = -6.22%, 95% confidence interval [CI]: -8.02% to -4.41%, I⊃2; = 90.0%) (Nalisa D L, 2024). Subgroup and meta-regression analyses found that patients without metabolism had more significant weight loss, and patients treated for 24 weeks had more prominent weight reduction compared to those treated for 12 - 20 weeks[3].
Application in Chinese adults with overweight or obesity:
A mid-term analysis of a randomized, two-part (low dose up to 6mg and high dose 9mg), double-blind, placebo-controlled Phase 2 trial conducted in Chinese adults with overweight or obesity showed that Maz was safe and effective in this population during the 24-week treatment period, bringing about significant and clinically meaningful weight loss [2]. In the study, adults with overweight (BMI ≥ 24 kg/m²) accompanied by hyperphagia and/or at least one obesity-related comorbidity, or adults with obesity (BMI ≥ 28 kg/m²) were randomly assigned to receive weekly Maz at doses of 3mg, 4.5mg, 6mg or a matching placebo. The results showed that from the baseline to the 24th week, the mean percentage change in body weight was -6.7% (standard error 0.7) in the 3mg Maz group, -10.4% (0.7) in the 4.5mg group, -11.3% (0.7) in the 6mg group, and 1.0% (0.7) in the placebo group. Compared with the placebo, the treatment difference ranged from -7.7% to -12.3% (all p < 0.0001) [2].
In conclusion, as an innovative dual-target agonist, through multiple mechanisms such as regulating blood glucose, promoting fat metabolism, and inhibiting appetite, Maz can effectively improve the blood glucose levels of patients with type 2 metabolism and help obese people lose weight. It injects new vitality into the treatment of metabolic diseases and is expected to alleviate the global burden of obesity and related diseases.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Zhang B is a highly - qualified scholar linked with multiple renowned organizations. These include Peking Union Medical College, Chinese Academy of Medical Sciences -Peking Union Medical College, - Japan Friendship Hospital, Guizhou Equipment Mfg Polytech, Shanghai Jiao Tong University, Universiti Utara Malaysia, Yingkou Institute of Technology, Zhejiang University, and Peking Union Medical College Hospital. Such diverse institutional connections highlight his broad academic and research background.
In terms of research, Zhang B has an extensive range of subject categories. His expertise covers Endocrinology & Metabolism, General & Internal Medicine, Oncology, Cardiovascular System & Cardiology, and Radiology, Nuclear Medicine & Medical Imaging. His work in these fields indicates his in - depth knowledge and significant contributions to advancing medical science and improving healthcare practices. Zhang B is listed in the reference of citation [1].
