Mazdutide

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Potential Health Benefits of Mazdutide
Key Takeaways
What is Mazdutide?
How Mazdutide Works
Chemical Structure of Mazdutide
Research on Mazdutide
Associated Side Effects of Mazdutide
Mazdutide and Body Weight
Mazdutide and Liver Fat Content
Mazdutide and Blood Pressure
Mazdutide Dosage – Focusing on Mazdutide 9 mg
FAQ
Blog
Reference

Potential Health Benefits of Mazdutide

Mazdutide offers a range of health benefits, including promoting weight loss, improving blood sugar and lipid levels, enhancing cardiovascular health, and bolstering bone health. These improvements contribute to overall metabolic and physiological well-being.

Promotes weight loss [1-7]
Improves blood sugar levels [2-4, 6, 8]
Improves lipid levels [4-8]
Improves cardiovascular health [9-22]
Improves bone health [23-29]

Key Takeaways

Mazdutide offers a range of health benefits, notably promoting weight loss, improving blood sugar and lipid levels, enhancing cardiovascular health, and bolstering bone health. These benefits collectively contribute to improved metabolic and physiological well-being.
Mazdutide is a GLP-1 and glucagon receptor dual agonist, known as IBI362, OXM-3, or LY3305677. It functions by increasing insulin secretion, lowering blood sugar levels, promoting weight loss, increasing energy expenditure, and improving fat metabolism in the liver.
Mazdutide works by activating the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor. This activation stimulates insulin release, increases the volume of insulin-producing beta cells, reduces glucagon secretion, slows stomach emptying (enhancing satiety), and increases energy expenditure.
As a long-acting synthetic peptide with a fatty acid side chain, mazdutide has an extended duration of action, allowing for convenient once-a-week administration.
Side effects associated with mazdutide are relatively uncommon. Reported side effects may include abdominal distension, decreased appetite, diarrhea, nausea, and vomiting. However, it is important to note that these side effects have not been conclusively linked to Mazdutide and could be coincidental.

What is Mazdutide?

Mazdutide, also known as IBI362, OXM-3, or LY3305677, is a glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. This long-acting synthetic peptide uses a fatty acid side chain to prolong the duration of action. As a result, mazdutide can be administered once a week. By activating the GLP-1 receptor and glucagon receptor in the body, mazdutide increases insulin secretion, lowers blood sugar levels, promotes weight loss, increases energy expenditure, and improves fat metabolism in the liver.

How Mazdutide Works

Mazdutide activates the glucagon-like peptide-1 (GLP-1) receptor and glucagon receptor in the body. GLP-1 receptor activation stimulates the release of insulin from the pancreas, increases the volume of insulin-producing cells called beta cells, and reduces the secretion of glucagon (a hormone that lowers blood sugar levels). In addition, GLP-1 receptor activation acts on appetite centers in the brain and slows down the emptying of the stomach, resulting in an increased feeling of fullness. On the other hand, glucagon receptor activation promotes weight loss by increasing energy expenditure and decreasing energy intake. Both GLP-1 and glucagon receptor activation also produce beneficial effects such as decreased bone breakdown, cardioprotection, and increased excretion of sodium (salt) by the kidneys via urine.

Chemical Structure of Mazdutide

IMG

Research on Mazdutide

A. Promotes Weight Loss

Both GLP-1 and glucagon receptor activation by mazdutide promote weight loss by acting on appetite centers in the brain, slowing down the emptying of the stomach, increasing the feeling of fullness, increasing energy expenditure, and decreasing energy intake.

Mazdutide’s ability to induce weight loss is backed by several studies:

In Chinese subjects with overweight or obesity, the administration of subcutaneous (injected into the fatty tissue) 9 mg of mazdutide once weekly for 12 weeks produced a mean body weight loss of 9.5%. This result represents a significant placebo-adjusted weight loss, as the reduction in body weight was notably higher with mazdutide compared to what was observed in the placebo group. Unlike placebo, mazdutide achieved more significant reductions in waist circumference and body mass index with no serious adverse events among Chinese subjects. The distinction of placebo-adjusted weight loss highlights the true effectiveness of mazdutide, as it factors in the general weight loss effects that might occur without active medication.
A phase 1b clinical trial included adults (aged 20-70 years) with type 2 diabetes for at least 3 months who received a GLP-1 and glucagon receptor agonist at different doses (3/6/9/12 mg). [2] The participants were randomly assigned to receive once-weekly subcutaneous injections of a GLP-1 and glucagon receptor agonist, placebo, or dulaglutide 1.5 mg over 12 weeks. Results showed that the GLP-1 and glucagon receptor agonist produced significant weight loss compared with placebo and dulaglutide.
A study evaluated the effects of mazdutide in healthy volunteers and subjects with type 2 diabetes. [3] All of the subjects received mazdutide or placebo with doses escalated over 12 or 16 weeks. Results showed reductions in mean body weight from baseline with increasing doses, with the largest change observed on Day 29, in the mazdutide-treated group compared with placebo. No serious adverse events were observed during mazdutide treatment.
A total of 43 patients with type 2 diabetes were enrolled in a study. The patients received once-weekly mazdutide (3.0 mg, 4.5 mg, or 6 mg), placebo, or dulaglutide (1.5 mg) subcutaneously for 12 weeks. One of the primary assessments in this study was the change in body weight from baseline. Mazdutide treatment at all doses significantly reduced body weight compared with dulaglutide and placebo. This change in body weight was a crucial outcome measure, highlighting mazdutide’s effectiveness in weight management for people with type 2 diabetes. The findings indicate that, in addition to glycemic control, mazdutide could offer significant benefits in terms of change in body weight, an important factor in the overall management of type 2 diabetes.
A study evaluated the safety, tolerability, pharmacokinetics, and efficacy of mazdutide at doses 3.0 mg, 4.5 mg, and 6.0 mg in Chinese adults with overweight or obesity. [5] The participants received a once-weekly subcutaneous injection of mazdutide (3.0 mg, 4.5 mg, and 6.0 mg) or placebo for 12 weeks with an additional 8 weeks of safety follow-up. Results showed that mazdutide treatment at all doses was well tolerated and showed a body weight-lowering effect compared with placebo.
The weight loss effects of mazdutide were assessed in diet-induced obese (DIO) and streptozotocin-induced diabetic mice. A group of mice received a single subcutaneous dose of mazdutide at 30 nmol/kg while another group received semaglutide at a dose of 60 nmol/kg. At the end of the treatment period, mazdutide reduced body weight to a greater extent (33%) and decreased the food intake of the subjects by 50% compared to semaglutide, exhibiting superior body weight loss. In addition, the mazdutide-treated mice experienced a 70% reduction in fat mass, further emphasizing its effectiveness in reducing body weight and fat mass significantly more than semaglutide.
A phase 1 study assessed the safety and tolerability of single ascending subcutaneous doses of mazdutide (6 doses: 0.03 mg to 5.0 mg) or placebo in healthy subjects. On Day 8, results showed that the change from baseline in body weight reached a maximum of 2.4 kg with the 5 mg dose versus 0.5 kg only for the placebo, and this effect was sustained through Day 29. This outcome demonstrated excellent weight loss with the 5 mg dose of mazdutide, highlighting its potential as an effective weight management solution. To further quantify the effectiveness of mazdutide, the weight from baseline versus the placebo was compared, providing a clearer understanding of mazdutide’s impact in weight reduction compared to the control group. This comparison of weight from baseline versus placebo underlines the significance of mazdutide’s role in weight management strategies.

B. Improves Blood Sugar Levels

Mazdutide can help stabilize blood sugar (glucose) levels by stimulating the body to produce more insulin via GLP-1 activation. Additionally, it plays a role in improving insulin sensitivity, which further aids in maintaining normal blood sugar levels. With increased insulin production and enhanced insulin sensitivity, the blood sugar levels stay within a normal range. This effect is crucial because insulin allows blood sugar to enter the cells and be used as a source of energy for various cellular functions. The glucose-lowering effects of mazdutide are a key component of its therapeutic action, especially beneficial for individuals managing type 2 diabetes.

Evidence suggests that mazdutide can help lower blood sugar levels in patients with type 2 diabetes:

A phase 1b clinical trial included adults (aged 20-70 years) with type 2 diabetes for at least 3 months who received a GLP-1 and glucagon receptor agonist at different doses (3/6/9/12 mg). [2] The participants were randomly assigned to receive once-weekly subcutaneous injections of a GLP-1 and glucagon receptor agonist (doses between 0.5-12 mg), placebo, or dulaglutide 1.5 mg over 12 weeks. At week 12, participants who received the three highest doses of the GLP-1 and glucagon receptor agonist significantly reduced the daily plasma glucose compared to those who received a placebo and dulaglutide.
A study evaluated the effects of mazdutide in healthy volunteers and subjects with type 2 diabetes. [3] All of the subjects received mazdutide or placebo with doses escalated over 12 or 16 weeks. On Day 29, the fasting glucose levels of the mazdutide-treated group were significantly decreased from baseline with increasing doses compared to the placebo-treated group. No serious adverse events were observed during mazdutide treatment.
A total of 43 patients with type 2 diabetes received once-weekly mazdutide (3.0 mg, 4.5 mg, or 6 mg), placebo, or dulaglutide (1.5 mg) subcutaneously for 12 weeks. [4] Primary outcomes showed that mazdutide was associated with increased safety and tolerability. Secondary outcomes showed a reduction in glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and post-mixed-meal tolerance test (post-MTT) glucose levels – all of which are a measure of blood sugar levels. Mazdutide reduced blood sugar levels more effectively and had lesser side effects compared with dulaglutide and placebo.
The weight loss effects of mazdutide were assessed in diet-induced obese (DIO) and streptozotocin-induced diabetic mice. [6] A group of mice received a single subcutaneous dose of mazdutide at 30 nmol/kg while another group received semaglutide at a dose of 60 nmol/kg. At the end of the treatment period, a single subcutaneous dose of mazdutide significantly reduced the blood sugar levels of both diet-induced obese and streptozotocin-induced diabetic mice by up to 65%.
In a phase 2 clinical study of mazdutide in Chinese patients with type 2 diabetes, it was found that the treatment resulted in higher tolerability and safety. [8] Researchers further confirmed that mazdutide’s tolerability and safety were similar to other GLP-1 class drugs. In addition, mazdutide treatment improved HbA1c levels by 1.67% and reduced body weight by an average of 7.11%. The treatment also produced multiple benefits to the patients such as reductions in blood lipids, liver enzymes, and blood pressure.

C. Improves Lipid Levels

Lipids are fatty compounds that are required by the body for energy storage, vitamin absorption, and hormone production. While they are important for various bodily functions, high levels of lipids such as cholesterol and triglycerides (blood fat) can significantly increase the risk of cardiovascular disease, stroke, and other life-threatening conditions as they can narrow or obstruct the blood vessels.

Interestingly, GLP-1 activation by mazdutide modulates key enzymes of lipid metabolism in the liver. This in turn reduces the production of lipids and other fats. Furthermore, the action of mazdutide can improve hepatic fat metabolism, addressing one of the key issues in metabolic syndromes like non-alcoholic fatty liver disease (NAFLD). By enhancing the liver’s ability to process and metabolize fats, mazdutide potentially reduces the accumulation of fat in the liver, thereby lowering the risk of liver-related complications that are often associated with high lipid levels.

Studies show that mazdutide can help reduce high lipid levels due to obesity and diabetes:

A total of 43 patients with type 2 diabetes were grouped into three. Group 1 received once-weekly mazdutide (3.0 mg, 4.5 mg, or 6 mg), group 2 received a placebo, and group 3 received dulaglutide (1.5 mg) subcutaneously for 12 weeks. At week 12, more pronounced reductions in waist circumference, body mass index (BMI), blood pressure, cholesterol, and triglyceride levels were observed in the mazdutide group compared with placebo and dulaglutide treatment. The improvements in these parameters were evaluated based on baseline versus placebo and dulaglutide, highlighting the efficacy of mazdutide. The comparison with baseline values provided a clear perspective on the therapeutic impact of mazdutide, emphasizing its effectiveness over the placebo and even against an established treatment like dulaglutide in terms of reducing waist circumference and percent change in body weight.
A study evaluated the safety, tolerability, pharmacokinetics, and efficacy of mazdutide at doses 3.0 mg, 4.5 mg, and 6.0 mg in Chinese adults with overweight or obesity. The participants received a once-weekly subcutaneous injection of mazdutide (3.0 mg, 4.5 mg, and 6.0 mg) or placebo for 12 weeks with an additional 8 weeks of safety follow-up. At week 12, the mazdutide-treated group exhibited significant reductions in blood pressure, HbA1c (a measure of blood sugar over the past 3 months), fasting plasma glucose, fasting insulin, cholesterol, and triglyceride levels compared to the placebo-treated group. To quantify these results, the percent change in each of these parameters from baseline was calculated, providing a clear and measurable understanding of mazdutide’s impact on various metabolic health indicators. This percent change analysis is crucial in demonstrating the drug’s efficacy and guiding future clinical decisions regarding its use in managing obesity and related metabolic conditions.
A study evaluated the effects of mazdutide in diet-induced obese (DIO) and streptozotocin-induced diabetic mice. [6] A group of mice received a single subcutaneous dose of mazdutide at 30 nmol/kg while another group received semaglutide at a dose of 60 nmol/kg. On Day 18, the mice treated with mazdutide exhibited a 70% reduction in triglyceride levels compared with the semaglutide-treated mice. A significant reduction in ketones (a byproduct of fat breakdown) was also observed in the mazdutide-treated mice.
A phase 1 study assessed the safety and tolerability of single ascending subcutaneous doses of mazdutide (6 doses: 0.03 mg to 5.0 mg) or placebo in healthy subjects. This study had a primary endpoint of evaluating the changes in fasting triglyceride levels. On Day 5, the subjects treated with mazdutide had significant reductions in the mean fasting triglyceride levels compared to the placebo-treated group. The reduction in triglyceride levels was a key measure in achieving the primary endpoint of the study, demonstrating the potential effectiveness of mazdutide in lipid metabolism. Furthermore, the results suggest that mazdutide may offer significant benefits in managing dyslipidemia, reinforcing its therapeutic potential as indicated by its primary endpoint.
A phase 2 clinical study of mazdutide in Chinese patients with type 2 diabetes showed that the treatment improved HbA1c levels by 1.67% and reduced body weight by an average of 7.11%. [8] Significant reductions in blood lipids, liver enzymes, and blood pressure were also observed. In addition, mazdutide treatment was safe and well tolerated by the patients.

D. Improves Cardiovascular Health

GLP-1 activation by mazdutide can be beneficial to heart health possibly by promoting weight loss and improving blood sugar and lipid levels. This in turn can help lower the risk of heart disease associated with obesity, diabetes, and abnormally high lipid levels.

The beneficial effects of GLP-1 activation are backed by several studies:

A total of 33,457 patients were included in an analysis of several clinical trials assessing the benefits of GLP-1 receptor agonists. [9] Based on the study, GLP-1R agonists appear to have cardioprotective properties likely via reduction of body weight, blood sugar, blood pressure, and major adverse cardiac events.
Studies reported that GLP-1 receptor agonists not only improve well-known cardiovascular risk factors such as blood sugar, weight, or arterial hypertension but also other factors such as blood flow to the heart and other cardiovascular functions. [10-14]
A review of 98 studies comprising 60,080 patients found that GLP-1 receptor agonists reduced major adverse cardiovascular events by 14%, all-cause mortality by 12%, hospital admission for heart failure by 11%, and the composite kidney outcome by 21% with no increased risk of adverse effects. [15]
In patients with type 2 diabetes with high cardiovascular risk, the administration of a GLP-1 receptor agonist was associated with a consistent reduction in atherothrombotic events (rupture of plaques and blood clot formation in the heart). [16]
A study reported that GLP-1 receptor agonists can help lower cardiovascular risk by suppressing low-grade inflammation, dilation of blood vessels, and increased sodium excretion by the kidneys. [17]
In adults with newly diagnosed type 2 diabetes mellitus, the administration of GLP-1 receptor agonists was associated with a lower risk of cardiovascular events. [18]
Studies suggested that GLP-1 receptor agonists can be included as part of cardiovascular risk reduction strategy due to their ability to produce beneficial effects on body weight, blood sugar levels, heart function, blood pressure, and lipid metabolism. [19-21]
An analysis of several clinical trials assessing the efficacy and safety of GLP-1 receptor agonists in adult patients with type 2 diabetes mellitus found that the treatment can significantly reduce the risk of deaths related to heart disease and hospitalization rate. [22]

E. Improves Bone Health

GLP-1 activation by mazdutide can also improve bone health by controlling blood sugar levels, promoting bone formation, and inhibiting bone resorption (breakdown). This in turn can help lower the risk of bone disorders such as osteoporosis and fractures.

Studies show that GLP-1 activation can help protect against bone disorders and improve overall bone health:

A study reported that GLP-1 receptor agonists can prevent osteoporosis by inhibiting signaling pathways associated with bone breakdown. [23]
In a rat model of bone loss, GLP-1 receptor agonist administration promoted bone formation and increased bone mass and quality by increasing the number of bone-forming cells called osteoblasts. [24]
In patients with type 2 diabetes, GLP-1 receptor agonist administration improved bone quality. [25]
A study found that GLP-1 receptor agonists promote bone formation and inhibit bone breakdown by acting on the Wnt and calcitonin pathways. [26]
In diabetic rats, GLP-1 receptor agonist administration improved the deficient bone formation and bone structure associated with blood sugar intolerance. [27]
In type 2 diabetes mellitus patients, GLP-1 receptor agonists were associated with a decreased bone fracture risk compared with placebo treatment or other anti-diabetic drugs. [28]
In non-diabetic postmenopausal women, the administration of a GLP-1 receptor agonist was associated with reduced osteoporosis risk. [29]

Associated Side Effects of Mazdutide

Mazdutide side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on mazdutide. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of mazdutide. Despite this, it was listed as a side effect associated with mazdutide even though these associated side effects are very uncommon.

Side effects associated with mazdutide may include the following:

Abdominal distension
Decreased appetite
Diarrhea
Nausea
Vomiting

Mazdutide and Body Weight

Clinical trials of mazdutide have been particularly focused on its impact on body weight, with preliminary results indicating its efficacy in promoting weight loss. This is achieved through a multifaceted approach: by enhancing feelings of fullness and reducing appetite, the drug helps manage caloric intake, a crucial aspect of weight loss. Additionally, the increased energy expenditure facilitated by mazdutide aids in burning calories more efficiently, further contributing to weight reduction. These combined effects not only address the physical aspects of weight loss but also provide potential improvements in overall metabolic health. As obesity and type 2 diabetes continue to present significant health challenges globally, the development of mazdutide represents an important step forward in managing these conditions more effectively, with the promise of improving the quality of life for those affected.

Mazdutide and Liver Fat Content

Mazdutide, an innovative pharmaceutical agent in development, shows promising potential in the realm of weight management, particularly for individuals with obesity and type 2 diabetes. As a dual agonist of the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor, Mazdutide operates on a unique mechanism of action, targeting two critical pathways involved in metabolic regulation. Its ability to stimulate insulin secretion while simultaneously reducing blood sugar levels positions it as a potentially effective treatment for weight-related issues. Moreover, the drug’s influence on energy expenditure and fat metabolism in the liver, including the reduction of liver fat content, further underscores its potential as a significant player in weight management strategies. In clinical trials, the effectiveness of Mazdutide has been evaluated not just in terms of weight reduction but also in its ability to lower baseline liver fat content, a key indicator of improved liver health in patients with obesity and type 2 diabetes. This focus on reducing baseline liver fat content enhances the prospect of mazdutide offering more comprehensive treatment solutions for obesity and diabetes, with broader metabolic benefits.

Clinical trials of mazdutide have been particularly focused on its impact on body weight, with preliminary results indicating its efficacy in promoting weight loss. This is achieved through a multifaceted approach: by enhancing feelings of fullness and reducing appetite, the drug helps manage caloric intake, a crucial aspect of weight loss. Additionally, the increased energy expenditure facilitated by mazdutide aids in burning calories more efficiently, further contributing to weight reduction. Moreover, mazdutide has shown potential in improving liver fat content, an important factor in metabolic health, especially in individuals with obesity-related liver conditions. In these trials, mazdutide’s effect on markers of liver health has also been assessed, providing insight into its potential benefits in reducing liver inflammation and damage often associated with excessive liver fat.

These combined effects not only address the physical aspects of weight loss but also provide potential improvements in overall metabolic health. The reduction in liver fat content brought about by mazdutide is particularly significant, as excessive liver fat is a common complication of obesity and type 2 diabetes, contributing to the risk of non-alcoholic fatty liver disease (NAFLD). By managing liver fat content effectively, mazdutide may help mitigate this risk, offering a comprehensive approach to treating obesity and its associated metabolic disorders. As obesity and type 2 diabetes continue to present significant health challenges globally, the development of mazdutide represents an important step forward in managing these conditions more effectively, with the promise of improving the quality of life for those affected.

Mazdutide and Blood Pressure

Mazdutide, an emerging therapeutic option in the management of metabolic disorders, may also have implications for blood pressure regulation. As a dual agonist of the glucagon-like peptide-1 (GLP-1) receptor and glucagon receptor, mazdutide primarily targets metabolic pathways, influencing blood sugar levels, insulin secretion, and fat metabolism. These metabolic effects, in turn, can have a secondary impact on cardiovascular health, including blood pressure management. The potential of mazdutide to improve cardiovascular health, a common concern in patients with obesity and type 2 diabetes, is a critical aspect of its overall therapeutic profile.

The relationship between metabolic disorders and hypertension is well-established, with insulin resistance and obesity being key risk factors for high blood pressure. By addressing these underlying metabolic issues, mazdutide may contribute to the normalization of blood pressure levels. Moreover, the drug’s effect on weight loss and improved lipid profiles can further reduce the strain on the cardiovascular system, potentially lowering the risk of hypertension. While the primary focus of Mazdutide’s clinical trials has been on its metabolic effects, ongoing research is likely to shed more light on its impact on blood pressure. Additionally, these trials are crucial in identifying any significant risks associated with Mazdutide, particularly in relation to blood pressure changes. If proven effective, mazdutide could offer a multifaceted approach to treating patients with metabolic syndrome, where hypertension often coexists with other metabolic abnormalities, thus enhancing the overall management of these patients’ health.

Mazdutide Dosage – Focusing on Mazdutide 9 mg

Mazdutide, as a novel pharmacological agent, is tailored for once-weekly administration, offering a convenient dosing regimen for patients. Its development as a long-acting dual agonist of the glucagon-like peptide-1 (GLP-1) receptor and glucagon receptor makes it suitable for chronic conditions like obesity and type 2 diabetes, where consistent, long-term management is crucial. The dosing strategy for mazdutide is designed to maintain therapeutic levels in the body over an extended period, ensuring continuous efficacy while minimizing the burden of frequent medication intake. This aspect of the drug is particularly beneficial for improving patient adherence and satisfaction, which are vital for the successful management of chronic diseases.

In the context of dosing, mazdutide 9 mg represents a specific dosage strength that is being explored in clinical trials. This dosage aims to strike a balance between efficacy and tolerability, ensuring that patients receive an optimal amount of the drug to achieve the desired therapeutic effects while minimizing potential side effects. The choice of dosage, such as the 9 mg dose, would be based on clinical trial data, which assesses the drug’s performance at various strengths. The flexibility in dosing options, including the availability of different strengths like mazdutide 9 mg, allows for personalized treatment plans tailored to individual patient needs and responses. As research progresses, the optimal dosing regimens of mazdutide will become clearer, paving the way for its potential inclusion in the treatment arsenal for metabolic disorders.

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FAQ

What is Mazdutide?

Mazdutide is a novel medication with agonist activity for glucagon and GLP-1 receptors.

What is the purpose of Mazdutide?

Mazdutide is being developed for the treatment of obesity and associated comorbidities, as well as type 2 diabetes. A key aspect of its mechanism in treating obesity involves its ability to increase energy expenditure, which plays a significant role in weight reduction and metabolic improvement. By promoting an increase in energy expenditure, mazdutide helps to burn more calories, contributing to effective weight management, a crucial element in the treatment of obesity and its related health issues. This action, combined with its potential in managing type 2 diabetes, positions mazdutide as a multifaceted treatment option in the realm of metabolic health.

How does Mazdutide work?

Mazdutide works by targeting glucagon and GLP-1 receptors, which play roles in glucose and appetite regulation. This mechanism of action makes it particularly effective in addressing issues related to metabolic disorder, a condition often characterized by imbalances in glucose metabolism and weight management. By influencing these receptors, mazdutide not only helps in regulating blood sugar levels but also aids in controlling appetite, both of which are crucial factors in the management of metabolic disorder.

Is Mazdutide currently available on the market?

Mazdutide is currently not available on the market as it is still under development. It is undergoing phase III clinical trials for obesity and type 2 diabetes and is not expected to be submitted for FDA approval until these pre-marketing clinical trials are completed and the results remain favorable. As such, any off-label usage of mazdutide before FDA approval and outside the scope of these clinical trials is not recommended.

What are the primary benefits of Mazdutide?

The primary benefits of mazdutide include potential weight loss and improved glycemic control, underlining its multiple metabolic benefits. A notable aspect of this weight loss is the reduced waist circumference observed in patients, which is an important indicator of improved metabolic health and a reduction in risk factors associated with cardiovascular diseases and diabetes.

In addition to these significant advantages, mazdutide is also being explored for its potential impact on serum uric acid levels, a key factor in various metabolic disorders like gout and kidney stones. By potentially influencing serum uric acid levels, mazdutide could offer a comprehensive approach to managing metabolic health, addressing a spectrum of issues including weight, blood sugar, and serum uric acid imbalances.

Furthermore, its efficacy in these areas, particularly in achieving reduced waist circumference, may position mazdutide as an alternative or adjunct to metabolic surgery for certain patients, broadening the scope of treatment options in metabolic health management. This holistic effect underscores the multiple metabolic benefits of mazdutide, making it a potentially valuable therapeutic option for patients with complex metabolic needs, including those predisposed to hyperuricemia and its associated risks.

Is Mazdutide suitable for people with type 1 diabetes?

Mazdutide is primarily intended for individuals with type 2 diabetes, where its mechanism of action plays a crucial role in lowering blood glucose levels. This effect is particularly important for managing the condition, as type 2 diabetes is characterized by elevated blood glucose due to insulin resistance or insufficient insulin production. The use of mazdutide in type 1 diabetes, however, has not been established, as type 1 diabetes involves an autoimmune disease that leads to the destruction of insulin-producing cells, requiring different treatment strategies. Therefore, mazdutide’s role remains focused on type 2 diabetes, where its ability to lower blood glucose can significantly benefit patients in managing their blood sugar levels more effectively. The distinction between type 1 and type 2 diabetes is crucial in the application of treatments, as the underlying causes and progression of these conditions differ markedly, with autoimmune factors playing a central role in type 1 diabetes.

Are there any common side effects associated with Mazdutide?

Common side effects may include mild to moderate gastrointestinal symptoms, such as nausea and diarrhea.

Can Mazdutide be taken orally?

Mazdutide is typically administered via subcutaneous injections, not orally, distinguishing it from many traditional weight loss drugs that are often taken in pill form. This mode of administration is important for the effectiveness of mazdutide, as it ensures direct delivery of the medication into the body’s tissues, optimizing its metabolic effects. The use of injections over oral intake is a common approach for many biologic treatments, including several weight loss drugs, to ensure that the active ingredients are not degraded in the digestive system and can work more efficiently in the body.

Is Mazdutide recommended for long-term use?

The long-term use of mazdutide would depend on clinical trials and regulatory approval. These trials are not only pivotal in determining the efficacy and safety of mazdutide over extended periods but also play a crucial role in decisions to improve drug availability for long-term treatment.

How often is Mazdutide administered?

The dosing frequency of mazdutide may vary depending on the specific treatment regimen being investigated in clinical trials.

Is Mazdutide used in combination with other medications?

Mazdutide may be used in combination with other medications for certain medical conditions, but this would be determined through clinical trials and medical guidance.

Can Mazdutide be self-administered?

Healthcare professionals typically administer Mazdutide through subcutaneous injections.

What is the typical duration of Mazdutide treatment?

The duration of mazdutide treatment may vary depending on the specific clinical trial or treatment plan.

Are there any dietary restrictions when taking Mazdutide?

Specific dietary recommendations may be provided by healthcare professionals based on individual patient needs. Additionally, considering mazdutide’s potential impact on serum uric acid levels, patients might be advised to moderate foods high in purines, which can increase serum uric acid, as part of their overall treatment plan. This dietary adjustment, alongside mazdutide’s treatment, aims to enhance the drug’s effectiveness in managing conditions associated with elevated serum uric acid, bringing multiple metabolic benefits. Such holistic management, combining medication with dietary modifications, underscores the comprehensive approach to improving metabolic health with mazdutide.

Is Mazdutide safe for pregnant or breastfeeding individuals?

Safety during pregnancy and breastfeeding should be discussed with a healthcare provider, as the data may be limited.

Can Mazdutide cause hypoglycemia?

Hypoglycemia risk with mazdutide may depend on its use in combination with other diabetes medications and individual factors.

Is Mazdutide approved by regulatory authorities?

Approval status would depend on the progress of clinical trials and regulatory decisions.

Are there any age restrictions for Mazdutide use?

Age restrictions, if any, for mazdutide would be specified in the product labeling and clinical guidance, especially considering its role in reducing body weight and managing metabolic disorders. Such information is crucial to ensure safe and appropriate use across different age groups, aligning with the medication’s intended effects on metabolic health.

Can Mazdutide be used for weight loss alone, without diabetes?

Mazdutide’s use for weight loss alone would depend on its regulatory approval and medical guidance.

Is Mazdutide available in different dosage forms?

The availability of different dosage forms may be determined by the manufacturer and regulatory authorities.

Can Mazdutide be used to treat obesity in children?

The use of mazdutide in children would depend on clinical trials and regulatory approvals for that population.

Are there any special storage requirements for Mazdutide?

Storage requirements would typically be provided in the product’s packaging and instructions.

How does Mazdutide compare to other weight loss medications?

Comparative efficacy and safety studies would provide insights into how mazdutide stacks up against other medications, particularly in its role in promoting insulin secretion, a key aspect in the management of type 2 diabetes. This comparison is essential for understanding mazdutide’s unique therapeutic benefits and potential advantages over existing treatments.

Can Mazdutide be used in conjunction with a weight loss program?

Combining mazdutide with a weight loss program may be considered as part of a comprehensive treatment approach.

Can Mazdutide help with reducing appetite?

Mazdutide’s action on GLP-1 receptors may help reduce appetite in some individuals.

Are there any special considerations for older adults taking Mazdutide?

Healthcare providers may consider age-related factors when prescribing mazdutide.

Can Mazdutide be used to prevent diabetes in people at risk?

The use of mazdutide for diabetes prevention would depend on clinical trial outcomes.

Does Mazdutide require dose adjustments for people with kidney problems?

Dose adjustments may be necessary for individuals with kidney problems, depending on clinical guidance.

Can Mazdutide interact with other medications?

Potential drug interactions should be discussed with a healthcare provider.

Is Mazdutide effective for long-term weight maintenance?

Long-term weight maintenance with mazdutide would depend on individual factors and clinical outcomes. As it continues through its clinical development, the duration and sustainability of weight loss effects with mazdutide will be more thoroughly evaluated. This aspect of clinical development is crucial in determining the long-term efficacy and safety of the drug for ongoing weight management. Understanding these outcomes will provide essential information for healthcare providers to guide patients appropriately in their long-term treatment plans with mazdutide.

What is the mechanism of action of Mazdutide on glucose regulation?

Mazdutide’s action on GLP-1 receptors contributes to improved glucose regulation. The efficacy of this mechanism is currently being evaluated in pivotal clinical trials, which are essential for determining the full therapeutic potential and safety profile of mazdutide in glucose management. These trials will provide critical data to validate the drug’s effectiveness in clinical settings.

Can Mazdutide cause allergic reactions?

Allergic reactions are possible with any medication, so it’s important to watch for symptoms and seek medical attention if they occur.

Can Mazdutide be used to treat polycystic ovary syndrome (PCOS)?

The use of mazdutide for PCOS would depend on clinical trial outcomes and medical guidance.

How is Mazdutide different from other GLP-1 agonists?

Differences in efficacy, safety, and dosing may exist, but they would need to be determined through clinical trials and studies.

Can Mazdutide be used for weight loss surgery patients?

The use of mazdutide in weight loss surgery patients would depend on clinical guidance and individual circumstances. Particularly in obese patients who have undergone or are considering weight loss surgery, mazdutide may offer an alternative or adjunct therapy, depending on their specific health profile and the recommendations of healthcare providers. For patients with moderate to severe obesity, mazdutide could potentially complement surgical interventions by aiding in weight management and improving metabolic health post-surgery. However, the decision to use mazdutide in such cases must be carefully evaluated on a case-by-case basis, considering the unique needs and medical history of each patient.

Is Mazdutide suitable for people with heart conditions?

Mazdutide’s safety and suitability for individuals with heart conditions should be discussed with a healthcare provider, especially since cardiovascular health can be closely linked with obesity, type 2 diabetes, and other major diseases. It is essential to consider how mazdutide might interact with existing heart conditions or medications used to manage them.

Can Mazdutide be taken with or without food?

The dosing instructions for mazdutide, including whether it should be taken with or without food, would be provided by the manufacturer.

How does Mazdutide affect insulin sensitivity?

Mazdutide’s action on GLP-1 receptors may improve insulin sensitivity.

Can Mazdutide be used for weight loss maintenance after initial success?

The use of mazdutide for weight loss maintenance would depend on clinical guidance and individual needs.

Is Mazdutide available in generic form?

The availability of generic forms of mazdutide would depend on patent expiration and regulatory approval.

What are the side effects of the drug mazdutide?

Mazdutide has been reported to have mild side effects, including upper respiratory tract infection, diarrhea, decreased appetite, nausea, urinary tract infection, abdominal distension (bloating), and vomiting. These side effects are generally well-tolerated and may lessen as treatment continues.

Who makes mazdutide?

Mazdutide, also known as OXM3, is a GLP-1 and GCGR receptor dual agonist developed by Innovent through a licensing agreement with Eli Lilly and Company. This collaboration with Eli Lilly and Company, a prominent player in the pharmaceutical industry, has significantly contributed to the advancement and development of Mazdutide, leveraging the expertise and resources of both companies. The partnership underscores the commitment of both Innovent and Eli Lilly and Company to bring innovative treatments to the market, particularly in the field of metabolic health and diabetes management.

What is the Lilly drug for obesity?

Eli Lilly’s drug for obesity is tirzepatide, sold under the brand name Mounjaro for type 2 diabetes, and has been cleared by the FDA to treat obesity. Tirzepatide is part of a new class of drugs that includes semaglutide, known as Ozempic for diabetes, and Wegovy for weight loss.

What is Survodutide?

Survodutide is a glucagon/GLP-1 receptor dual agonist that activates both the GLP-1 and glucagon receptors, critical for controlling metabolic functions. It is co-invented by Boehringer Ingelheim and Zealand Pharma and is part of Boehringer Ingelheim’s research and development portfolio in the cardio-renal-metabolic disease areas.

Should I switch from semaglutide to tirzepatide?

Switching from semaglutide to tirzepatide may be an option for individuals who are not achieving their treatment goals with semaglutide alone. However, it is important to consult with a healthcare professional before making any changes to your medication regimen.

What's the difference between semaglutide and tirzepatide?

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, while semaglutide is simply a GLP-1 receptor agonist. GLP-1s act by triggering insulin production to reduce blood sugar levels.

What is the most effective weight loss injection?

Among weight loss injections, Wegovy and Zepbound (brand name for Eli Lilly’s tirzepatide) are FDA-approved and have shown significant results. Zepbound has led to a 21% weight loss in adults using the highest dose, while Wegovy has led to about a 15% weight loss.

What is the generic name for tirzepatide?

The generic name for tirzepatide is simply “tirzepatide.” It is sold under the brand names Zepbound and Mounjaro.

What is the mechanism of action of mazdutide?

Mazdutide is a dual glucagon-like peptide 1 receptor agonist (GLP-1RA) and glucagon receptor agonist. By activating both GLP-1R and glucagon receptors, it helps regulate appetite, and metabolism, and improve glucose control.

Can non-diabetics take GLP-1?

Yes, GLP-1 agonists, originally developed for type 2 diabetes, have also been shown to be effective for weight loss in non-diabetic patients with obesity or overweight BMI when combined with diet and exercise. In addition to these benefits, some GLP-1 agonists have been observed to influence blood uric acid levels, which could be beneficial for patients with conditions related to high uric acid. They are not used in patients with type 1 diabetes. This expanded range of effects demonstrates the versatility of GLP-1 agonists in managing various aspects of metabolic health.

What is the difference between Phase 2a and 2b clinical trials?

Phase 2a clinical trials are focused specifically on dosing requirements, involving a small number of patients administered the drug in different quantities to evaluate efficacy.

Is Mounjaro approved for weight loss?

Yes, Mounjaro’s active ingredient, tirzepatide, is approved for weight loss under the brand name Zepbound.

How does tirzepatide work for weight loss?

Tirzepatide works for weight loss by increasing insulin production, decreasing sugar production by the liver, and slowing down food metabolism.

What is the new diabetic drug with Eli Lilly?

The new diabetic drug by Eli Lilly is Mounjaro, also known as tirzepatide. It is a first-of-its-kind treatment that can help control blood sugar and potentially aid in weight loss.

Is retatrutide the same as tirzepatide?

No, retatrutide and tirzepatide are not the same. Retatrutide is a drug for obesity, acting as a triple hormone receptor agonist of GLP-1, GIP, and GCGR receptors. Tirzepatide, on the other hand, is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, primarily used for diabetes treatment and weight loss.

How much weight can you lose with Rybelsus?

With Rybelsus, a medication for type 2 diabetes, people have lost an average of 4.4 to 8.1 pounds in one year in clinical studies. It’s important to note that Rybelsus is not a weight loss drug and its effect on weight may vary from person to person.

What is the most effective weight loss pill?

The most effective weight loss pills for those looking to lose weight include Contrave, Qsymia, phentermine, and orlistat. These prescription medications have been recognized for their effectiveness in weight loss efforts.

What does Innovent Biologics Inc. do?

Innovent Biologics Inc. focuses on the development and commercialization of high-quality biological drugs, striving to bring high-quality innovative medicines to the market. The company leverages its team’s experience and strategic collaborations with international companies to advance China’s biopharmaceutical industry and improve the availability of quality drugs for the general population. This commitment to developing high-quality innovative medicines is central to Innovent’s mission, as they aim to address unmet medical needs and enhance the overall healthcare landscape.

Innovent has assembled a global team comprised of experts in the development and commercialization of high-quality biopharmaceutical products. This international team includes many specialists with global expertise. Additionally, the company has formed strategic partnerships with renowned entities such as Eli Lilly, Roche, Sanofi, Adimab, Incyte, and MD Anderson Cancer Center, among other international collaborators.

Reference

Ji, L., Gao, L., Jiang, H., Yang, J., Yu, L., Wen, J., Cai, C., Deng, H., Feng, L., Song, B., Ma, Q., & Qian, L. (2022). Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. EClinicalMedicine, 54, 101691. https://doi.org/10.1016/j.eclinm.2022.101691.

Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial

In this phase 1b trial, researchers investigated the safety and effectiveness of mazdutide, a novel GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity. Participants were given different doses of mazdutide or a placebo, and the study found that mazdutide, especially at higher doses, was well-tolerated with mild to moderate side effects. It also led to significant weight loss compared to the placebo, indicating its potential for treating moderate-to-severe obesity. Further, larger phase 2 trials are planned to explore high-dose mazdutide’s efficacy and safety in this population.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561728/.
Urva, S., Coskun, T., Loh, M. T., Du, Y., Thomas, M. K., Gurbuz, S., Haupt, A., Benson, C. T., Hernandez-Illas, M., D’Alessio, D. A., & Milicevic, Z. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet (London, England), 400(10366), 1869–1881. https://doi.org/10.1016/S0140-6736(22)02033-5.

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial

In a 12-week study, the safety, pharmacokinetics, and pharmacodynamics of LY3437943, a multi-receptor agonist for type 2 diabetes and obesity treatment, were investigated. Participants with type 2 diabetes were randomly assigned to receive weekly injections of LY3437943, placebo, or dulaglutide. LY3437943 demonstrated an acceptable safety profile, dose-proportional pharmacokinetics suitable for weekly dosing, and significant reductions in plasma glucose, HbA1c, and body weight compared to placebo. These findings support the potential for further phase 2 development of LY3437943 for type 2 diabetes and obesity management.

You can read the abstract of the article at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02033-5/fulltext.
Available from https://diabetesjournals.org/diabetes/article/71/Supplement_1/333-OR/146313/333-OR-Oxyntomodulin-Analog-LY3305677-LY-Improves.
Jiang, H., Pang, S., Zhang, Y., Yu, T., Liu, M., Deng, H., Li, L., Feng, L., Song, B., Han-Zhang, H., Ma, Q., Qian, L., & Yang, W. (2022). A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (LY3305677) in Chinese patients with type 2 diabetes. Nature communications, 13(1), 3613. https://doi.org/10.1038/s41467-022-31328-x.

A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (LY3305677) in Chinese patients with type 2 diabetes

In a randomized, placebo-controlled phase 1b study (ClinicalTrials.gov: NCT04466904), the safety and efficacy of IBI362 (LY3305677), a dual agonist targeting glucagon-like peptide-1 (GLP-1) and glucagon receptors, were evaluated in Chinese patients with type 2 diabetes (T2D). Across three cohorts with 43 enrolled T2D patients, IBI362 (at doses of 3.0 mg, 4.5 mg, or 6.0 mg) was administered once weekly, along with placebo or open-label dulaglutide (1.5 mg) subcutaneously for 12 weeks. IBI362 demonstrated good tolerability, with common treatment-emergent adverse events including diarrhea, decreased appetite, and nausea. The study revealed clinically meaningful reductions in glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and post-mixed-meal tolerance test (post-MTT) glucose levels, indicating a favorable safety profile and potential efficacy in lowering blood glucose in Chinese patients with T2D.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232612/.
Ji, L., Jiang, H., An, P., Deng, H., Liu, M., Li, L., Feng, L., Song, B., Han-Zhang, H., Ma, Q., & Qian, L. (2021). IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study. EClinicalMedicine, 39, 101088. https://doi.org/10.1016/j.eclinm.2021.101088.

IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study

In a randomized, placebo-controlled, multiple ascending dose phase 1b study, the safety, tolerability, pharmacokinetics, and efficacy of IBI362 (LY3305677), a dual agonist targeting glucagon-like peptide-1 and glucagon receptors, were assessed in Chinese adults with overweight or obesity. Participants received once-weekly subcutaneous injections of IBI362 or placebo in three ascending dose cohorts over 12 weeks. The study, conducted from June 15th, 2020, to January 15th, 2021, included 36 participants. No treatment discontinuations due to safety reasons or serious adverse events were reported. Gastrointestinal adverse events and decreased appetite were the most common, mostly mild in severity. The estimated percent changes in mean body weight from baseline to week 12 demonstrated significant reductions for participants receiving IBI362 compared to the placebo group.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374649/.
Available from https://diabetesjournals.org/diabetes/article/70/Supplement_1/682-P/140621/682-P-Novel-Dual-Glucagon-and-Glucagon-Like.
Available from https://diabetesjournals.org/diabetes/article/70/Supplement_1/106-OR/139552.
Available from https://clinicaltrials.gov/ct2/show/NCT04965506?cond=NCT04965506&draw=2&rank=1.
Jia, X., Alam, M., Ye, Y., Bajaj, M., & Birnbaum, Y. (2018). GLP-1 Receptor Agonists and Cardiovascular Disease: a Meta-Analysis of Recent Cardiac Outcome Trials. Cardiovascular drugs and therapy, 32(1), 65–72. https://doi.org/10.1007/s10557-018-6773-2.

GLP-1 Receptor Agonists and Cardiovascular Disease: a Meta-Analysis of Recent Cardiac Outcome Trials

This study conducted a meta-analysis of four recent cardiovascular outcomes trials (ELIXA, LEADER, SUSTAIN-6, and EXSCEL) to investigate the cardioprotective properties of Glucagon-like peptide-1 receptor agonists (GLP-1R agonists), a class of antihyperglycemic therapy. The meta-analysis, encompassing 33,457 patients, revealed that GLP-1R agonists significantly reduced all-cause mortality and cardiovascular mortality compared to placebo. When focusing on long-acting agents alone, there was a significant reduction in major adverse cardiac events and non-fatal strokes. The findings suggest that GLP-1R agonists may possess cardioprotective properties, potentially through modifying metabolic parameters such as glycemic control, weight loss, and blood pressure improvement. Further studies are recommended to compare cardiovascular outcomes among different agents in this class.

You can read the abstract of the article at https://link.springer.com/article/10.1007/s10557-018-6773-2.
Del Olmo-Garcia, M. I., & Merino-Torres, J. F. (2018). GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes. Journal of diabetes research, 2018, 4020492. https://doi.org/10.1155/2018/4020492.

GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes

Diabetes mellitus is a prevalent chronic disease with a rising incidence, and cardiovascular disease remains the leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). In selecting treatments for T2DM, prioritizing cardiovascular safety and preventing cardiovascular complications is crucial. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stand out among available drugs, demonstrating not only safety but potential benefits for cardiovascular health. These benefits extend beyond addressing traditional cardiovascular risk factors like glycemic control, dyslipidemia, weight, and hypertension, potentially impacting endothelial function, coronary ischemia, and heart failure. Notably, clinical trials have shown cardiovascular superiority with liraglutide and semaglutide compared to placebo. Although the mechanisms underlying their cardiovascular benefits are not fully understood, incorporating these findings into routine clinical practice algorithms is desirable. This review aims to explore the multifaceted actions of GLP-1 RAs on cardiovascular risk factors and established cardiovascular disease.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902002/.
Coke, L. A., Deedwania, P. C., Hinnen, D., Magwire, M., & Miller, N. H. (2022). GLP-1 receptor agonists and cardiovascular outcomes in patients with type 2 diabetes: Clinical evidence and best practice. Journal of the American Association of Nurse Practitioners, 34(2), 418–440. https://doi.org/10.1097/JXX.0000000000000661.

GLP-1 receptor agonists and cardiovascular outcomes in patients with type 2 diabetes: Clinical evidence and best practice

Cardiovascular disease (CVD) significantly contributes to mortality and morbidity in individuals with type 2 diabetes (T2D), impacting both life expectancy and healthcare costs. Despite the low attainment of recommended glycemic targets in the United States, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are now favored as add-on therapies to metformin for improving glycemic control, especially in patients with T2D and established or high risk of atherosclerotic CVD or chronic kidney disease. Cardiovascular outcomes trials (CVOTs) consistently demonstrate that GLP-1RAs pose no additional cardiovascular risk compared to placebo. Certain GLP-1RAs, including liraglutide, dulaglutide, and subcutaneous semaglutide, have shown significantly lower major adverse cardiovascular events compared to placebo and are approved for this indication. However, achieving improved outcomes in clinical settings requires organized, systematic, and coordinated patient management approaches. This article delves into T2D management, focusing on cardiovascular risk, CVOT findings, and the clinical impact of GLP-1RAs in managing hyperglycemia. Practical guidance is provided for healthcare providers involved in the care of patients with T2D and cardiovascular risk outside of diabetes clinics or endocrinology centers.

You can read the full article at https://journals.lww.com/jaanp/fulltext/2022/02000/glp_1_receptor_agonists_and_cardiovascular.32.aspx.
Sheahan, K. H., Wahlberg, E. A., & Gilbert, M. P. (2020). An overview of GLP-1 agonists and recent cardiovascular outcomes trials. Postgraduate medical journal, 96(1133), 156–161. https://doi.org/10.1136/postgradmedj-2019-137186.

An overview of GLP-1 agonists and recent cardiovascular outcomes trials

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly recognized as a crucial therapeutic option for individuals with type 2 diabetes (T2D), offering the ability to reduce glycated hemoglobin, induce weight loss, and carry a low risk of hypoglycemia. Over the past four years, seven cardiovascular outcomes trials (CVOTs) involving lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide, and oral semaglutide have been conducted. These trials consistently demonstrate the non-inferiority of GLP-1 RAs for cardiovascular outcomes, with many indicating their superiority. These findings have significantly influenced guidelines for the pharmacological management of T2D. This review article will explore GLP-1 RA therapy, assess the seven reported CVOTs, and discuss their implications on current guidelines and future therapeutic approaches.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042958/.
Heuvelman, V. D., Van Raalte, D. H., & Smits, M. M. (2020). Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes. Cardiovascular research, 116(5), 916–930. https://doi.org/10.1093/cvr/cvz323.

Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes

Type 2 diabetes mellitus (T2DM) stands as one of the most prevalent global diseases, affecting around 415 million individuals. Characterized by elevated blood glucose levels, T2DM often coexists with comorbidities, including cardiovascular disease. Treatment strategies for T2DM aim to lower glucose levels through lifestyle modifications or medical interventions. Among these, glucagon-like peptide 1 (GLP-1) has emerged as a therapeutic option. However, GLP-1 faces rapid degradation, limiting its glycemic impact. GLP-1 receptor agonists (GLP-1RAs), resistant to degradation, have gained attention for their positive effects on cardiovascular health. Both preclinical and clinical evidence highlight the abundance of GLP-1 receptors in the heart, with GLP-1 stimulation exhibiting various cardiovascular benefits. This review explores the impact of GLP-1RAs on heart rate, blood pressure, microvascular function, lipids, and inflammation, drawing insights from human mechanistic studies and linking these effects to the improved cardiovascular outcomes observed in numerous trials.

You can read the full article at https://academic.oup.com/cardiovascres/article/116/5/916/5673388?login=false.
Honigberg, M. C., Chang, L. S., McGuire, D. K., Plutzky, J., Aroda, V. R., & Vaduganathan, M. (2020). Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review. JAMA cardiology, 5(10), 1182–1190. https://doi.org/10.1001/jamacardio.2020.1966.

Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review

Significant strides have been made in recent randomized clinical trials highlighting the cardiovascular benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for individuals with type 2 diabetes. However, these promising outcomes have not translated into widespread use, particularly among cardiologists. Noteworthy trials on albiglutide, dulaglutide, liraglutide, and injectable semaglutide have demonstrated favorable cardiovascular effects, while the newly approved oral semaglutide is undergoing further regulatory evaluation. Current professional guidelines recommend GLP-1RA therapy for mitigating cardiovascular risk in patients with type 2 diabetes and established atherosclerotic cardiovascular disease or multiple risk factors, independent of glucose control or background antihyperglycemic therapy. Additional indications for GLP-1RA use include obesity and advanced chronic kidney disease. This review emphasizes the safety, tolerability, and cardiovascular benefits of GLP-1RAs, providing cardiologists with practical insights for initiating and managing this therapy in patients with type 2 diabetes and established cardiovascular risks.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744318/.
Sattar, N., Lee, M. M. Y., Kristensen, S. L., Branch, K. R. H., Del Prato, S., Khurmi, N. S., Lam, C. S. P., Lopes, R. D., McMurray, J. J. V., Pratley, R. E., Rosenstock, J., & Gerstein, H. C. (2021). Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. The lancet. Diabetes & endocrinology, 9(10), 653–662. https://doi.org/10.1016/S2213-8587(21)00203-5.

Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials

In this meta-analysis incorporating recent data from AMPLITUDE-O, the cardiovascular benefits and risks of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes were systematically examined. The study, encompassing eight trials with 60,080 patients, revealed that GLP-1 receptor agonists, irrespective of structural homology, significantly reduced major adverse cardiovascular events (MACE) by 14%, all-cause mortality by 12%, hospital admission for heart failure by 11%, and the composite kidney outcome by 21%. Notably, there was no increase in the risk of severe hypoglycemia, retinopathy, or pancreatic adverse effects. These findings underscore the robust cardiovascular benefits of GLP-1 receptor agonists in individuals with type 2 diabetes, emphasizing their potential as a therapeutic option beyond glycemic control.

You can read the abstract of the article at https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00203-5/fulltext.
Marx, N., Husain, M., Lehrke, M., Verma, S., & Sattar, N. (2022). GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes. Circulation, 146(24), 1882–1894. https://doi.org/10.1161/CIRCULATIONAHA.122.059595.

GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes

Patients with type 2 diabetes face a heightened risk of cardiovascular diseases, encompassing myocardial infarction, stroke, heart failure, and cardiovascular mortality. Large cardiovascular outcome trials involving innovative glucose-lowering agents, specifically SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA), have consistently revealed substantial reductions in major adverse cardiovascular events and heart failure hospitalizations. This evidence has prompted a transformative shift in the approach to treating type 2 diabetes, with both diabetes and cardiology guidelines strongly recommending the use of SGLT2i and/or GLP-1 RA. These recommendations are grounded in evidence-based benefits for reducing cardiovascular risk in high-risk individuals with type 2 diabetes, irrespective of additional glucose control requirements. While initially designed for glucose management, GLP-1 RA, by activating the GLP-1 receptor, not only lower blood glucose and enhance postprandial glucose metabolism but also induce satiety and promote weight loss by stimulating GLP-1R in hypothalamic neurons. Cardiovascular outcome trials consistently demonstrate a marked and uniform reduction in atherothrombotic events, especially in patients with established atherosclerotic cardiovascular disease. Despite this evidence, the utilization of these drugs remains suboptimal, emphasizing the need for increased awareness and implementation in the cardiology community.

You can read the full article at https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.122.059595?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org.
Boyle, J. G., Livingstone, R., & Petrie, J. R. (2018). Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review. Clinical science (London, England : 1979), 132(15), 1699–1709. https://doi.org/10.1042/CS20171299.

Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review

Type 2 diabetes (T2D) is associated with the risk of both cardiovascular (CV) complications, such as myocardial infarction and stroke, and microvascular complications, including retinopathy, nephropathy, and neuropathy. While glucose-lowering effectively prevents microvascular issues, its impact on CV complications remains uncertain. Glucagon-like peptide-1 (GLP-1) agonists, potent glucose-lowering agents, exhibit potential benefits on traditional factors like body weight, blood pressure (BP), and LDL cholesterol, as well as non-traditional risk factors like low-grade inflammation and endothelial dysfunction. Results from four major CV outcome trials with GLP-1 agonists (ELIXA, LEADER, SUSTAIN-6, and EXSCEL) are available, with ongoing trials involving dulaglutide and albiglutide. LEADER and SUSTAIN-6 demonstrated reduced rates of major adverse CV events with active GLP-1 treatment, while ELIXA and EXSCEL did not. This review explores the mechanisms of GLP-1 receptor agonists on the CV system and analyzes trial design and outcomes. Contrary to the idea that all GLP-1 agonists uniformly reduce CV disease in T2D, the authors argue that CV benefits are specific to agents with longer-lasting agonism at the GLP-1 receptor. The mechanisms involve effects on body weight, BP, LDL-cholesterol, and glucose, with additional pleiotropic effects like inflammation suppression, vasodilation, and natriuresis likely playing a role.

You can read the abstract of the article at https://portlandpress.com/clinsci/article-abstract/132/15/1699/71791/Cardiovascular-benefits-of-GLP-1-agonists-in-type?redirectedFrom=fulltext.
Yang, C. T., Yang, C. Y., Ou, H. T., & Kuo, S. (2020). Comparative cardiovascular safety of GLP-1 receptor agonists versus other glucose-lowering agents in real-world patients with type 2 diabetes: a nationwide population-based cohort study. Cardiovascular diabetology, 19(1), 83. https://doi.org/10.1186/s12933-020-01053-0.

Comparative cardiovascular safety of GLP-1 receptor agonists versus other glucose-lowering agents in real-world patients with type 2 diabetes: a nationwide population-based cohort study

In this study, the researchers aimed to assess the real-world cardiovascular safety of glucagon-like peptide-1 receptor agonists (GLP-1ra) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i), sulfonylureas (SU), and insulin in individuals with newly-diagnosed type 2 diabetes (T2D). Using Taiwan’s National Health Insurance Research Database, the prevalent new-user cohort design included a diverse representation of real-world T2D patients treated with GLP-1ra. Propensity score matching ensured baseline comparability among groups. The primary outcome, a composite of cardiovascular disease (CVD) events, was assessed until the end of 2015. Results indicated that GLP-1ra use was associated with a lower risk of composite CVD events compared to DPP-4i, SU, and insulin. Subgroup analyses suggested a greater cardiovascular benefit of GLP-1ra over DPP-4i in individuals without established CVD. The study contributes additional evidence supporting the cardiovascular safety of GLP-1ra in a diverse real-world T2D population.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293792/.
Sivertsen, J., Rosenmeier, J., Holst, J. J., & Vilsbøll, T. (2012). The effect of glucagon-like peptide 1 on cardiovascular risk. Nature reviews. Cardiology, 9(4), 209–222. https://doi.org/10.1038/nrcardio.2011.211.

The effect of glucagon-like peptide 1 on cardiovascular risk

Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone, stimulating insulin secretion more significantly after oral nutrient intake than intravenous administration. In patients with type 2 diabetes mellitus, GLP-1 retains its insulinotropic activity. GLP-1-based treatments, including GLP-1 receptor agonists and dipeptidyl peptidase 4 inhibitors, demonstrate efficacy in reducing glucose levels and are standard therapies for type 2 diabetes. Beyond glucose regulation, these agents impact various cardiovascular parameters, encompassing blood pressure, endothelial function, body weight, cardiac metabolism, lipid metabolism, left ventricular function, atherosclerosis, and the response to ischemia-reperfusion injury. This review explores the multifaceted mechanisms targeted by GLP-1-based therapies, emphasizing recent advancements in incretin research relevant to cardiovascular risk, disease, and the use of GLP-1 receptor agonists in treatment.

You can read the abstract of the article at https://www.nature.com/articles/nrcardio.2011.211.
Reed, J., Kanamarlapudi, V., & Bain, S. (2018). Mechanism of cardiovascular disease benefit of glucagon-like peptide 1 agonists. Cardiovascular endocrinology & metabolism, 7(1), 18–23. https://doi.org/10.1097/XCE.0000000000000147.

Mechanism of cardiovascular disease benefit of glucagon-like peptide 1 agonists

GLUCAGON-LIKE PEPTIDE-1 (GLP-1)-based therapies effectively manage hyperglycemia in type 2 diabetes, yet the prevalence of diabetes-related cardiovascular comorbidity persists. GLP-1 exhibits cardiovascular-specific actions in both healthy individuals and those with cardiovascular conditions, and GLP-1 therapies have demonstrated cardiovascular improvements in diabetic patients. Operating through its receptor (GLP-1 receptor) at the cell surface, the precise mechanistic pathways underlying the cardiovascular benefits of GLP-1 therapies remain unclear. Interpretation of GLP-1 receptor agonism’s impact on cardiovascular disease from animal and human studies is challenging due to diverse experimental designs. This review focuses on recent insights from prolonged human GLP-1 therapy studies and outlines proposed mechanisms through which GLP-1 receptor agonism may mitigate cardiovascular disease.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739887/.
Lingvay, I., & Leiter, L. A. (2018). Use of GLP-1 RAs in Cardiovascular Disease Prevention: A Practical Guide. Circulation, 137(21), 2200–2202. https://doi.org/10.1161/CIRCULATIONAHA.117.032759.

Use of GLP-1 RAs in Cardiovascular Disease Prevention: A Practical Guide

The cardiovascular outcomes of sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like protein-1 receptor agonists (GLP-1 RAs) have led to a shift in the management of type 2 diabetes, emphasizing the need for cardiologists to familiarize themselves with these agents. This article underscores the importance of a team approach, involving cardiologists, primary care providers, and diabetologists, in prescribing these drugs and managing patient concerns. It specifically focuses on liraglutide, the first GLP-1 RA with a cardiovascular indication, detailing its cardiovascular benefits observed in the LEADER trial. The review addresses practical considerations, side effects, and dosing strategies for liraglutide, emphasizing its role in reducing major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease. The article also highlights important unanswered clinical questions related to combining liraglutide with other agents and its use in lower-risk patients without diabetes mellitus. Ultimately, it concludes that liraglutide should be integral to a comprehensive risk reduction plan for patients with diabetes and atherosclerotic cardiovascular disease.

You can read the abstract of the article at https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.032759?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
Marsico, F., Paolillo, S., Gargiulo, P., Bruzzese, D., Dell’Aversana, S., Esposito, I., Renga, F., Esposito, L., Marciano, C., Dellegrottaglie, S., Iesu, I., & Perrone Filardi, P. (2020). Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials. European heart journal, 41(35), 3346–3358. https://doi.org/10.1093/eurheartj/ehaa082.

Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials

The aim of this trial-level meta-analysis was to investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on major cardiovascular (CV) events and safety in patients with Type 2 diabetes mellitus (DM), both with and without established cardiovascular disease (CVD). The analysis of seven cardiovascular outcome trials (CVOTs) comprising 56,004 patients revealed that GLP-1 receptor agonists significantly reduced major adverse cardiovascular events (MACE), CV mortality, all-cause mortality, fatal and non-fatal stroke, and heart failure hospitalization in the entire population of DM patients. Although there was no significant effect on fatal and non-fatal myocardial infarction, a sensitivity analysis suggested a potential reduction. Importantly, no excess risk of hypoglycemia, pancreatitis, or pancreatic cancer was observed with GLP-1 receptor agonists compared to placebo. The findings indicate significant cardiovascular benefits of GLP-1 receptor agonists in both DM patients with and without established CVD.

You can read the full article at https://academic.oup.com/eurheartj/article/41/35/3346/5741382?login=false.
Xie, B., Chen, S., Xu, Y., Han, W., Hu, R., Chen, M., Zhang, Y., & Ding, S. (2021). The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment. Frontiers in pharmacology, 12, 697442. https://doi.org/10.3389/fphar.2021.697442.

The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment

The close relationship between diabetes mellitus and osteoporosis, along with the potential impact of anti-diabetic drugs on bone metabolism, has become a focus of attention. Type 2 diabetes mellitus (T2DM) is associated with bone fragility, an increased risk of fractures, and compromised bone repair. Anti-diabetic drugs used in T2DM treatment may have adverse effects on bone health. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as promising agents for T2DM treatment, with studies suggesting potential anti-osteoporotic effects by regulating blood sugar levels, promoting bone formation, and inhibiting bone resorption. However, the specific impact of GLP-1RAs on fracture risk and osteoporosis in clinical practice remains unclear. This review summarizes current research on GLP-1RAs in the context of diabetic osteoporosis, postmenopausal osteoporosis, and glucocorticoid-induced osteoporosis, exploring potential mechanisms, such as the GLP-1R/MAPK signaling pathway, GLP-1R/PI3K/AKT signaling pathway, and Wnt/β-catenin pathway, associated with GLP-1RAs and osteoporosis. Further exploration is needed to define the specific role and mechanisms of GLP-1RAs in bone metabolism across different types of osteoporosis.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243369/.
Meng, J., Ma, X., Wang, N., Jia, M., Bi, L., Wang, Y., Li, M., Zhang, H., Xue, X., Hou, Z., Zhou, Y., Yu, Z., He, G., & Luo, X. (2016). Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin. Stem cell reports, 6(4), 579–591. https://doi.org/10.1016/j.stemcr.2016.02.002.

Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin

The crucial role of glucagon-like peptide 1 (GLP-1) in bone remodeling is highlighted by its positive correlation with osteoblast activity. Despite the absence of the GLP-1 receptor in osteoblasts, the mechanism through which GLP-1 receptor agonists influence bone remodeling remains unclear. In a rat model of unloading-induced bone loss, the GLP-1 receptor agonist exendin-4 (Ex-4) demonstrated the ability to enhance bone formation, increasing both bone mass and quality. This effect was accompanied by elevated osteoblast numbers and serum bone formation markers, coupled with a reduction in adipocyte numbers. Interestingly, GLP-1 receptor was identified in bone marrow stromal cells (BMSCs) rather than osteoblasts. Ex-4 activation of GLP-1 receptor promoted osteogenic differentiation and hindered adipogenic differentiation in BMSCs through the regulation of PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling pathways. These findings shed light on the role of GLP-1 receptor in BMSC osteogenic differentiation, providing a molecular foundation for the therapeutic potential of GLP-1 in addressing osteoporosis.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834036/.
Mabilleau, G., Pereira, M., & Chenu, C. (2018). Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists. The Journal of endocrinology, 236(1), R29–R42. https://doi.org/10.1530/JOE-17-0278.

Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists

Type 2 diabetes mellitus (T2DM) not only results in bone fragility and an elevated risk of fractures but also introduces challenges in bone healing and other skeletal complications. Some anti-diabetic treatments for T2DM can further exacerbate skeletal issues. Therefore, an effective therapeutic approach for T2DM should not only focus on achieving optimal glycemic control but also on minimizing skeletal complications. Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used in T2DM treatment, exhibit positive effects on bone physiology, particularly bone quality. This review provides an overview of the direct and indirect impacts of GLP-1RAs on bone, emphasizing bone strength and novel mechanisms related to vasculature and hormonal regulation. Experimental studies highlight significant positive effects of GLP-1RAs on bone quality, though the mechanisms may vary among different GLP-1RAs. Despite a lack of conclusive clinical studies supporting their bone-protective effects, the potential of GLP-1RAs to enhance blood supply to bones holds promise, particularly for elderly T2DM patients with osteoporosis and heightened fracture risk.

You can read the full article at https://core.ac.uk/reader/132194032?utm_source=linkout.
Zhao, C., Liang, J., Yang, Y., Yu, M., & Qu, X. (2017). The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms. Frontiers in endocrinology, 8, 98. https://doi.org/10.3389/fendo.2017.00098.

The Impact of Glucagon-Like Peptide-1 on Bone Metabolism and Its Possible Mechanisms

The interaction between antidiabetic drugs and bone metabolism has garnered increased attention with the identification of a link between type 2 diabetes mellitus (T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists, a promising class of drugs for T2DM, are now under scrutiny for potential applications in bone tissue disorders. This review delves into the influence of GLP-1 on bone metabolism, highlighting its capacity to enhance bone mineral density and improve bone quality. However, the precise impact of GLP-1 on fracture risk remains to be unequivocally defined. The review also provides an overview of the current understanding of the molecular mechanisms through which GLP-1 affects bone metabolism, including the promotion of bone formation, inhibition of bone resorption, and modulation of their coordination. Molecular pathways and proteins such as Wnt and calcitonin associated with GLP-1 and bone tissue are discussed, emphasizing the need for further exploration and clarification of the specific processes and mechanisms governing the effects of GLP-1 on bone metabolism.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413504/.
Nuche-Berenguer, B., Moreno, P., Esbrit, P., Dapía, S., Caeiro, J. R., Cancelas, J., Haro-Mora, J. J., & Villanueva-Peñacarrillo, M. L. (2009). Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. Calcified tissue international, 84(6), 453–461. https://doi.org/10.1007/s00223-009-9220-3.

Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states

There is limited understanding of the role of glucagon-like peptide 1 (GLP-1) in bone resorption, unlike other hormones released after nutrient absorption. The relationship between osteoporosis and type 2 diabetes (T2D) remains unclear, but diabetes-related bone loss is linked to poor glucose homeostasis control. To investigate, streptozotocin-induced T2D and fructose-induced insulin-resistant rat models were compared to normal rats. GLP-1 or saline treatment was administered, and blood and bone samples were collected for analysis. In T2D and insulin-resistant models, certain bone markers were altered, and GLP-1 treatment showed insulin-independent anabolic effects, suggesting its potential as a therapeutic agent for addressing deficient bone formation and structure associated with glucose intolerance.

You can read the abstract of the article at https://link.springer.com/article/10.1007/s00223-009-9220-3.
Zhang, Y. S., Weng, W. Y., Xie, B. C., Meng, Y., Hao, Y. H., Liang, Y. M., & Zhou, Z. K. (2018). Glucagon-like peptide-1 receptor agonists and fracture risk: a network meta-analysis of randomized clinical trials. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 29(12), 2639–2644. https://doi.org/10.1007/s00198-018-4649-8.

Glucagon-like peptide-1 receptor agonists and fracture risk: a network meta-analysis of randomized clinical trials

In our network meta-analysis investigating the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk, data from randomized controlled trials were pooled to reveal a decreased risk of bone fractures associated with GLP-1 RAs. Among these agents, exenatide emerged as the most favorable option, exhibiting the lowest risk of fractures compared to other GLP-1 RAs. The study, registered with PROSPERO (CRD42018094433), included 54 eligible randomized control trials with 49,602 participants. Exenatide demonstrated the highest probability of being the safest choice concerning fracture risk, followed by dulaglutide, liraglutide, albiglutide, lixisenatide, and semaglutide. The findings suggest a beneficial association between GLP-1 RAs and reduced fracture risk in type 2 diabetes mellitus patients.

You can read the abstract of the article at https://link.springer.com/article/10.1007/s00198-018-4649-8.
Montes Castillo, M. C., Martínez Ramírez, M. J., Soriano Arroyo, R., Prieto Gomez, I., Segarra Robles, A. B., Garrido-Martínez, M., Santiago-Fernández, P., & Delgado Rodríguez, M. (2019). Glucagon-like peptide 1 and Glucagon-like peptide 2 in relation to osteoporosis in non-diabetic postmenopausal women. Scientific reports, 9(1), 13651. https://doi.org/10.1038/s41598-019-50117-z.

Glucagon-like peptide 1 and Glucagon-like peptide 2 in relation to osteoporosis in non-diabetic postmenopausal women

Osteoporosis, characterized by disrupted bone remodeling, exhibits a circadian rhythm influenced by the interplay between the intestine and bone tissue. Certain intestinal peptides, including glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2), have been implicated in bone health. In this study, non-diabetic postmenopausal women diagnosed with osteoporosis and age-matched controls without osteoporosis were examined. Postprandial plasma GLP-1 levels were significantly lower in osteoporosis cases, and lower GLP-1 values were associated with a heightened risk of osteoporosis. No significant associations were observed for postprandial GLP-2 or dipeptidyl-peptidase 4 activity with osteoporosis. These findings suggest a potential link between postprandial GLP-1 levels and osteoporosis risk in non-diabetic postmenopausal women, warranting further investigation.

You can read the full article at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754449/.

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Table of Contents

Potential Health Benefits of Mazdutide

Key Takeaways

What is Mazdutide?

How Mazdutide Works

Chemical Structure of Mazdutide

Research on Mazdutide

A. Promotes Weight Loss

B. Improves Blood Sugar Levels

C. Improves Lipid Levels

D. Improves Cardiovascular Health

E. Improves Bone Health

Associated Side Effects of Mazdutide

Mazdutide and Body Weight

Mazdutide and Liver Fat Content

Mazdutide and Blood Pressure

Mazdutide Dosage – Focusing on Mazdutide 9 mg

FAQ

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Is Mazdutide currently available on the market?

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How often is Mazdutide administered?

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Can Mazdutide be self-administered?

What is the typical duration of Mazdutide treatment?

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Is Mazdutide safe for pregnant or breastfeeding individuals?

Can Mazdutide cause hypoglycemia?

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Can Mazdutide cause allergic reactions?

Can Mazdutide be used to treat polycystic ovary syndrome (PCOS)?

How is Mazdutide different from other GLP-1 agonists?

Can Mazdutide be used for weight loss surgery patients?

Is Mazdutide suitable for people with heart conditions?

Can Mazdutide be taken with or without food?

How does Mazdutide affect insulin sensitivity?

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What is the Lilly drug for obesity?

What is Survodutide?

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What is the new diabetic drug with Eli Lilly?

Is retatrutide the same as tirzepatide?

How much weight can you lose with Rybelsus?

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