Danuglipron

Overall Health Benefits of Danuglipron

Danuglipron enhances health by improving blood sugar levels and facilitating weight loss, providing promising benefits for individuals with conditions like type 2 diabetes mellitus.

• Improves blood sugar levels [1-8]
• Promotes weight loss [2-8]

Key Takeaways of Danuglipron

• Danuglipron is a once-daily oral medication, which makes it convenient to take. It is also a long-acting medication, which means it provides blood sugar control for 24 hours.
• Danuglipron works by binding to the GLP-1 receptor on the surface of cells in the pancreas. This triggers the release of insulin, a hormone that helps the body use glucose for energy. Danuglipron also slows down stomach emptying, which helps to control blood sugar levels after meals.
• Danuglipron has been shown to improve blood sugar control in people with type 2 diabetes. In clinical trials, danuglipron was shown to significantly lower A1C levels, a measure of blood sugar control, compared to placebo. Danuglipron also helped people lose weight and reduce their risk of serious heart problems.
• Danuglipron is typically well-tolerated, with the most frequent side effects being nausea, vomiting, and diarrhea, which often resolve within a few weeks of initiating treatment.

What is Danuglipron?

Danuglipron is a small-molecule GLP-1 receptor agonist developed by Pfizer, a leading danuglipron manufacturer, as a once-daily oral treatment for adults with uncontrolled type 2 diabetes. It works by mimicking the effects of the hormone GLP-1, which is produced in the gut. GLP-1 helps to control blood sugar levels by stimulating the production of insulin and slowing down the emptying of the stomach. Danuglipron peptide has been shown to improve blood sugar control, help lose weight, and reduce risk factors of serious heart problems and diabetes-related diseases.

Danuglipron Mechanism of Action

The Trp33ECD is a specific part of a protein called GLP-1R where a drug called danuglipron binds to activate a signaling pathway in the body. The binding site on GLP-1R cannot activate the protein itself, but it is important for the binding of small GLP-1RA molecules. Two parts of the protein, ECL1 and ECL2, form connections with danuglipron and Trp33ECD respectively, while GLP-1RA peptides only interact with ECL2. This interaction with danuglipron activates a specific type of protein called class B1 GPCR, which stabilizes the GLP-1R’s binding area.

When the class B1 GPCR is activated, it produces a molecule called cyclic AMP (cAMP), which increases calcium levels and promotes the secretion of GLP-1 hormone. This increase in GLP-1 stimulates the growth of beta cells in the pancreas, which are important for insulin production. Additionally, danuglipron can partially activate another pathway called the beta-arrestin pathway, specifically a protein called betaArr2. It binds to a specific part of the protein called C-terminal TMD, resulting in the release of insulin-filled vesicles within the cell and reducing cell death. These effects help preserve the function of beta cells, increase insulin secretion, and contribute to lowering A1c levels.

Chemical Structure of Danuglipron

Research on Danuglipron

A. Improves Blood Sugar Levels

Danuglipron improves blood sugar levels through its mechanism of action as a GLP-1R agonist. When administered, danuglipron binds to the GLP-1 receptors, primarily located in the pancreas and the gastrointestinal tract. This binding triggers several physiological responses, including an increase in glucose-dependent insulin release from the pancreas. This means that danuglipron stimulates the secretion of insulin in response to elevated blood glucose levels, promoting glycemic control.

Additionally, danuglipron slows down the rate at which the stomach empties (gastric emptying), reducing post-meal spikes in blood sugar levels and contributing to better diabetes care. These combined effects enhance glycemic efficacy, helping individuals with diabetes maintain more stable and healthy blood sugar levels over time.

Clinical trials and animal studies show that danuglipron is effective in maintaining healthy blood sugar levels in people with type 2 diabetes:

1. A study assessed the effects of danuglipron in 98 patients who had type 2 diabetes and were already taking metformin, examining the potential benefits of combining danuglipron use with existing metformin use. [1] The subjects were divided into different groups and given increasing doses of danuglipron or a placebo for 28 days. The researchers closely monitored any side effects, conducted various tests, and checked vital signs and heart activity. The most commonly reported adverse events were mild, with the most common being nausea, indigestion, and vomiting. There were no concerning changes in laboratory test results among the groups. Heart rate slightly increased with danuglipron treatment, but there were no reported heart-related side effects. Systolic blood pressure decreased slightly, and diastolic blood pressure remained similar with danuglipron treatment compared to the placebo. The researchers did not find any significant issues in the electrocardiogram results. Overall, in this study with patients with type 2 diabetes, danuglipron was well-tolerated, and its safety matched what the researchers expected based on how it works on GLP-1R.
2. A randomized clinical trial published in the JAMA Network Open Journal tested the effectiveness, safety, and tolerance of a new oral drug called danuglipron, which activates a specific receptor involved in type 2 diabetes. [2] The study took place over 16 weeks and involved adults with type 2 diabetes who were not effectively managing their condition through diet and exercise alone. Some participants were also taking metformin. Metformin users remained on the same dose throughout the trial, with no alterations unless medically indicated. Patients on metformin should have maintained a stable dose for a minimum of 60 days before undergoing screening. Study participants were randomly assigned to receive either a placebo or one of the five target doses of danuglipron (2.5, 10, 40, 80, or 120 mg) taken orally twice a day with food for 16 weeks. Clinical and demographic characteristics were the same between treatment groups. The doses of danuglipron were gradually increased over the course of the study. The main outcomes measured were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight after 16 weeks. Safety was monitored throughout the study and for an additional 4 weeks. In all danuglipron groups, HbA1c and FPG levels were significantly reduced compared to the placebo at week 16. The reductions in HbA1c ranged from -1.16% to -0.86% compared to the placebo, and the reductions in FPG ranged from -33.24 mg/dL to -20.84 mg/dL compared to the placebo. Body weight was significantly reduced in the 80-mg and 120-mg dose danuglipron groups compared to the placebo, with reductions of -2.04 kg and -4.17 kg respectively. The most commonly reported side effects were nausea, diarrhea, and vomiting. One serious TEAE (treatment-emergent adverse event) was documented as related to the treatment, specifically acute cholecystitis in the 80-mg twice-daily group, involving a participant who had stopped taking the medication three days after randomization, and the event occurred 42 days after the last dose of the study medication. Thirteen participants experienced severe TEAEs while most participants experienced mild TEAEs.
3. A study looked at the effects of a new medication called danuglipron in Japanese people with type 2 diabetes. [3] Adult participants who were not able to control their diabetes with diet and exercise alone were enrolled in the study. They were randomly assigned to receive either a placebo or different danuglipron doses twice a day for 8 weeks. The main focus of the study was to assess the safety and tolerability of danuglipron, but the researchers also measured how the medication was absorbed and eliminated from the body, as well as its effects on blood sugar levels and body weight. The clinical data showed that the most common side effects experienced by the participants were nausea, vomiting, abdominal discomfort, diarrhea, and headache. However, these side effects were mostly mild or moderate in severity. The researchers found that the levels of danuglipron in the participants’ blood increased in proportion to the dose they received. After 8 weeks of treatment, the participants who took danuglipron had significant improvements in their blood sugar levels and body weight compared to those who received the placebo. Based on these findings, the researchers concluded that danuglipron is safe and well-tolerated in Japanese adults with type 2 diabetes. The medication effectively lowered blood sugar levels and helped with weight management.
4. An analysis of multiple studies found that danuglipron increased insulin levels in primates but not rodents. [4] When orally administered to healthy humans, the treatment produced dose-proportional increases in systemic exposure (NCT03309241). In addition, danuglipron was found to act in a similar way to GLP-1 in laboratory tests, such as increasing insulin release in response to glucose and reducing food intake in monkeys. It can also be taken orally by healthy humans.
5. In one study, researchers discovered a new group of chemicals called 5,6-dihydro-1,2,4-triazine derivatives. [5] By conducting different tests in the laboratory and living organisms, researchers found a specific compound called 42 that is very effective and selective in activating a protein called GLP-1R. This compound works like danuglipron by stimulating the production of a molecule called cAMP, which is important for certain bodily processes. When 42 and danuglipron were given in humanized mouse model with a specific genetic modification related to GLP-1R, it was observed that compound 42 significantly lowered the increase in blood sugar levels after eating and also reduced food intake. These effects lasted longer compared to danuglipron. Researchers concluded that compound 42 had comparable efficacy to danuglipron, which could be helpful in treating diabetes and obesity.
6. In a research study, 37 Japanese patients with type 2 diabetes who were not able to control their blood sugar levels with just diet and exercise took part. [6] The study was designed to investigate the safety, tolerability, how the body processes the medication (pharmacokinetics), and the effects on the body (pharmacodynamics) of a medication called danuglipron. The patients were randomly assigned to one of two groups: one group received a placebo (a fake pill) and the other group received increasing doses of danuglipron, starting at a lower dose and gradually increasing to higher danuglipron doses over the course of 8 weeks. The patients took the medication twice a day. The study found that taking multiple doses of danuglipron was generally safe for the Japanese patients with type 2 diabetes. Higher doses resulted in significant improvements in their fasting blood sugar levels, average daily blood sugar levels, levels of a substance called glycated hemoglobin (which indicates long-term blood sugar control), and body weight. Participants reported side effects such as nausea, vomiting, abdominal discomfort, diarrhea, and headache. No deaths occurred or serious treatment-related side effects were reported even with the highest dosage. There were no worrisome trends in the laboratory tests, heart monitoring (electrocardiogram), or abnormalities in vital signs.
7. In one study, researchers looked at the safety and effectiveness of a medication called PF-06882961 in patients with type 2 diabetes. [7] The study was done with a randomized, double-blind approach, meaning that some patients received the medication while others received a placebo (a dummy pill) without knowing which one they were taking. The study also included multiple doses of the medication, gradually increasing the amount given to participants. A total of 98 patients with type 2 diabetes with metformin use were included in the study. They were divided into 8 groups, with some groups receiving PF-06882961 and others receiving the placebo. The patients took the medication or placebo twice a day for 28 days. Throughout the study, the researchers measured the patients’ fasting blood sugar levels, average daily blood sugar levels, and body weight. The results showed that multiple doses of PF-06882961 were safe and well tolerated by patients with type 2 diabetes. The medication had positive effects on the participants’ blood sugar levels and body weight. Specifically, it helped reduce fasting blood sugar levels, average daily blood sugar levels, and body weight after 28 days in the danuglipron groups. Most of the side effects reported by the patients were mild, and the most commonly reported ones were nausea, upset stomach, diarrhea, headache, constipation, and vomiting. There were no deaths or serious side effects related to the use of PF-06882961. The laboratory tests, heart monitoring, and vital sign measurements did not show any concerning abnormalities.
8. A study enrolled 66 participants with type 2 diabetes mellitus. [8] Fifty-one subjects received PF-06882961 daily for 28 or 42 days while 15 subjects received PF-06882961 daily for 42 days. The subjects were randomized to receive PF-06882961 or a placebo in a 4:1 ratio. The researchers then titrated the daily dose until the glycemic target dose is reached. Results showed that PF-06882961 administration resulted in significant reductions in glucose (blood sugar) and weight in all treatment groups. Subjects who received PF-06882961 had reductions of 91 mg/dL over 28 days and 99 mg/dL over 42 days. The placebo group only had a reduction of 29 mg/dL in their blood sugar levels. The subjects treated with PF-06882961 also had body weight reductions of 5 kg over 28-42 days, compared with 2 kg in subjects who received a placebo. The adverse events related to the use of PF-06882961 were usually mild. The laboratory tests, heart monitoring, and vital sign measurements did not show any concerning abnormalities.

B. Promotes Weight Loss

One of the main ways that danuglipron helps with body weight loss is by affecting the appetite and food intake. GLP-1R agonists like danuglipron can help regulate the feeling of fullness (satiety) and reduce hunger, which can lead to decreased food consumption. This effect is thought to be mediated through interactions with the GLP-1 receptors in the brain that regulate appetite.

Furthermore, this weight loss drug can also slow down the emptying of the stomach, which prolongs the digestion process and helps individuals feel satisfied for a longer period after eating. This can help control cravings and prevent overeating. Additionally, danuglipron has been shown to have a positive impact on metabolism. It can enhance insulin secretion from the pancreas and improve the body’s response to insulin, which is responsible for regulating blood sugar levels. Improved insulin sensitivity can help control weight gain and promote weight loss.

The weight loss effects of danuglipron are backed by a number of clinical trials:

1. A research study was conducted to evaluate a new oral drug called danuglipron and its effectiveness in treating type 2 diabetes. [2] The study involved adults with type 2 diabetes who were not able to effectively manage their condition through diet and exercise alone. Some participants were also taking another diabetes medication called metformin. The participants were randomly divided into different groups. Some received a placebo (a dummy pill with no active ingredients), while others received varying doses of danuglipron (2.5, 10, 40, 80, or 120 mg). The study medication was taken orally twice a day with food for a total of 16 weeks. During the study, the doses of danuglipron were gradually increased. The main focus of the study was to measure the changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight after 16 weeks of treatment. Safety was also monitored throughout the study and for an additional 4 weeks. The results showed that in all the groups receiving danuglipron, there were significant reductions in HbA1c and FPG levels compared to the placebo-treated group after 16 weeks. The reductions in HbA1c ranged from -1.16% to -0.86% compared to the placebo, indicating improved blood sugar control. The reductions in FPG ranged from -33.24 mg/dL to -20.84 mg/dL compared to the placebo, showing decreased fasting blood sugar levels. In the 80-mg and 120-mg dose groups, there were also significant reductions in body weight, with reductions of -2.04 kg and -4.17 kg respectively, compared to the placebo. Participants reported side effects such as nausea, diarrhea, and vomiting. These side effects were observed in most participants across the different dose groups. Overall, the study showed that danuglipron had positive effects on blood sugar control and body weight in adults with type 2 diabetes.
2. A research study was conducted to investigate the effects of a new medication called danuglipron in Japanese individuals with type 2 diabetes who had a glycemic need. [3] The study enrolled adults who were unable to control their diabetes through diet and exercise alone. The participants were randomly assigned to receive either a placebo or different doses of danuglipron twice a day for a duration of 8 weeks and were monitored during the follow-up period. The primary objective of the study was to assess the safety and tolerability of danuglipron. Additionally, the researchers examined how the medication was absorbed and eliminated from the body. They also measured its impact on blood sugar levels and body weight. The results indicated that the most common side effects experienced by the participants included nausea, vomiting, abdominal discomfort, diarrhea, and headache. However, these side effects were generally mild or moderate in intensity. The researchers observed that the levels of danuglipron in the participants’ blood increased as the dose of the medication increased. After 8 weeks of treatment, the participants who received danuglipron demonstrated significant improvements in their blood sugar levels and body weight compared to those who received the placebo. Based on these findings, the researchers concluded that danuglipron is safe and well-tolerated in Japanese adults with type 2 diabetes. The study medication effectively lowered blood sugar levels and helped with weight management.
3. An analysis of multiple studies found that danuglipron increased insulin release in response to glucose and reduced food intake in monkeys. [4] When orally administered to healthy humans, the treatment produced dose-proportional increases in systemic exposure (NCT03309241). In addition, danuglipron was found to act in a similar way to GLP-1 in laboratory tests. By reducing food intake, danuglipron can help promote weight loss.
4. In a recent study, scientists made an exciting discovery of a new group of chemicals called 5,6-dihydro-1,2,4-triazine derivatives. [5] Through various laboratory tests and experiments on living organisms, they identified a specific compound known as 42, which displayed remarkable effectiveness and selectivity in activating a protein called GLP-1R. Compound 42, similar to danuglipron, operates by stimulating the production of a molecule called cAMP, which plays a crucial role in several bodily processes. When administered to mice with a particular genetic alteration related to GLP-1R, compound 42 exhibited significant reductions in post-meal blood sugar levels and food intake. Notably, these effects lasted longer when compared to danuglipron. Based on these findings, the researchers concluded that both compound 42 and danuglipron have positive effects on lowering blood sugar levels and reducing food intake. These effects hold potential for the treatment of conditions such as diabetes and obesity.
5. In a study involving 37 Japanese patients with type 2 diabetes who were struggling to control their blood sugar levels through diet and exercise alone, researchers aimed to investigate the safety, tolerability, pharmacokinetics (how the body processes the medication), and pharmacodynamics (effects on the body) of a medication called danuglipron. [6] The patients were randomly assigned to one of two groups: a placebo group that received fake pills, and a danuglipron group that received increasing doses of the medication over 8 weeks, starting from lower doses and gradually increasing to higher doses. The medication was taken twice a day. The study findings indicated that multiple doses of danuglipron were generally safe for the Japanese patients with type 2 diabetes. As the dose increased, more of the medication was present in their bodies, resulting in significant improvements in fasting blood sugar levels, average daily blood sugar levels, glycated hemoglobin levels (indicating long-term blood sugar control), and body weight. The most commonly reported side effects by the patients were mild or moderate, including nausea, vomiting, abdominal discomfort, diarrhea, and headache. No deaths or serious side effects related to the medication were reported. Furthermore, there were no adverse trends in laboratory tests, electrocardiogram readings, or abnormalities in vital signs.
6. In a clinical trial examining the safety and effectiveness of a medication called PF-06882961 in patients with type 2 diabetes, researchers employed a randomized, double-blind approach. [7] This meant that some patients were given the actual medication, while others received a placebo (a harmless dummy pill) without knowing which they were receiving. The study also involved administering multiple doses of the medication, gradually increasing the dosage throughout the trial. The study included 98 patients with type 2 diabetes who were already taking metformin. They were divided into eight groups, with some receiving PF-06882961 and others receiving the placebo. The participants took the medication or placebo twice a day for a duration of 28 days. Throughout the study, the researchers monitored the patients’ fasting blood sugar levels, average daily blood sugar levels, and body weight. The results indicated that multiple doses of PF-06882961 were well tolerated and safe for patients with type 2 diabetes. The medication demonstrated positive effects on blood sugar levels and body weight. Specifically, after 28 days of treatment, it helped reduce fasting blood sugar levels, average daily blood sugar levels, and body weight. Most of the side effects reported by patients were mild, with the most commonly experienced being nausea, upset stomach, diarrhea, headache, constipation, and vomiting. No deaths or serious side effects related to the use of PF-06882961 were reported. Laboratory tests, heart monitoring, and vital sign measurements did not reveal any concerning abnormalities.
7. In a study involving 66 participants with type 2 diabetes mellitus, the effects of PF-06882961 were investigated. [8] Out of the total participants, 51 individuals received daily doses of PF-06882961 for either 28 or 42 days, while the remaining 15 participants received daily doses of PF-06882961 for 42 days. The subjects were randomly assigned to receive either PF-06882961 or a placebo in a ratio of 4:1. The researchers adjusted the daily dose until the desired dosage was achieved. The results revealed that the administration of PF-06882961 led to significant reductions in blood glucose levels and weight across all treatment groups. Subjects who received PF-06882961 experienced reductions of 91 mg/dL over 28 days and 99 mg/dL over 42 days in their blood sugar levels. On the other hand, the placebo group only had a reduction of 29 mg/dL in their blood sugar levels. Additionally, the subjects treated with PF-06882961 exhibited weight reductions of 5 kg over the course of 28-42 days, whereas those who received the placebo experienced a weight reduction of 2 kg. The adverse events associated with the use of PF-06882961 were generally mild. Laboratory tests, heart monitoring, and vital sign measurements did not indicate any concerning abnormalities.

Discover the potential of peptides for weight loss and achieve your fitness goals today. Explore our comprehensive guide and products to kickstart your weight loss journey. Take the first step towards a healthier you!

Danuglipron Side Effects

Danuglipron 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 danuglipron. However, the issue wasn’t confirmed to be caused by the treatment and could have been a coincidence and not related to the use of danuglipron. Despite this, it was listed as a side effect associated with danuglipron even though these associated side effects are very uncommon.

Side effects associated with danuglipron may include the following:

• Nausea
• Diarrhea
• Dyspepsia (indigestion)
• Dizziness
• Vomiting

Danuglipron Dosage

The dosage of danuglipron is determined by your doctor based on your individual needs. The usual starting dose is 10 mg twice daily (BID). Your doctor may increase your dose gradually, up to a maximum of 120 mg BID, depending on how well you respond to the medication.

Danuglipron is taken by mouth, with or without food. It is important to take danuglipron at the same time(s) each day.

Danuglipron and Lotiglipron

Danuglipron and lotiglipron are both GLP-1 receptor agonists, which means they work by mimicking the effects of the natural hormone GLP-1. GLP-1 is produced in the small intestine and pancreas and helps to regulate blood sugar levels. It does this by increasing insulin production, slowing gastric emptying, and suppressing appetite.

Danuglipron and lotiglipron are taken as a tablet by mouth. They are both intended to keep blood sugar at healthy levels in people with type 2 diabetes. They also work to help people lose weight.

Danuglipron has been shown to be effective in reducing blood sugar levels and weight in people with type 2 diabetes. In a Phase 2 study, danuglipron was shown to reduce HbA1c (a measure of blood sugar control) by up to 1.16%, fasting plasma glucose (blood sugar levels after fasting) by up to 33.24 mg/dL, and body weight by up to 4.17 kg over 16 weeks. The most common side effects of danuglipron are nausea, vomiting, and diarrhea.

Lotiglipron was also shown to be effective in reducing blood sugar levels and weight in people with type 2 diabetes. However, the company developing lotiglipron, Pfizer, decided to terminate the clinical development of the drug due to concerns about liver safety. In some clinical studies, lotiglipron was associated with elevated levels of liver enzymes. These elevations were not severe and did not lead to liver failure or liver-related symptoms, but Pfizer decided to err on the side of caution and discontinue development.

The safety profile observed with danuglipron, including transaminase changes, appears to be comparable to that of the peptidic GLP-1R agonist class. This means that danuglipron is generally safe and well-tolerated, demonstrating a safety profile consistent with the mechanism of action of GLP-1R agonism.

Danuglipron Before and After

About Dr. George Shanlikian

Dr. George Shanlikian, renowned as the world’s best hormone therapy doctor, possesses expertise in various medical domains. These include Bio-Identical Hormone Replacement Therapy, Peptide Replacement Therapy, Anti-Aging Medicine, Regenerative Medicine, Stress Management, Nutrition Consulting, Nutritional Supplement Consulting, and Exercise Consulting.

Read more about him here: https://www.genemedics.com/dr-george-shanlikian-md-best-hormone-therapy-doctor

Read more success stories here:

Men’s Success Stories: https://www.genemedics.com/about-ghi/ghi-success-stories/mens-success-stories/

Women’s Success Stories: https://www.genemedics.com/about-ghi/ghi-success-stories/womens-success-stories/