Oral Non-peptide Glucagon

Benefits of Oral Non-peptide Glucagon-like Peptide-1 Receptor Agonists

Non-peptide glucagon-like peptide-1 receptor agonists enhance blood sugar control, promote weight loss, bolster heart health, reduce the necessity for insulin, and optimize the lipid profile. These attributes make them a valuable tool in managing type 2 diabetes and associated health concerns.

• Improves blood sugar control
• Promotes weight loss
• Improves heart health
• Reduces the need for insulin
• Improves lipid profile
• Improves quality of life

Key Takeaways of Oral Non-peptide Glucagon-like Peptide-1 Receptor Agonists

• The most significant advantage of oral non-peptide glucagon-like peptide-1 receptor agonists is their convenient oral route of administration, eliminating the need for injections and improving medication adherence.
• Oral non-peptide glucagon-like peptide-1 receptor agonists mimic the natural hormone GLP-1, effectively stimulating insulin secretion, suppressing glucagon release, and slowing gastric emptying, leading to improved blood sugar control.
• Oral non-peptide glucagon-like peptide-1 receptor agonists are known for their potential to promote weight loss, making them particularly valuable for individuals with both diabetes mellitus and obesity.
• Some oral non-peptide glucagon-like peptide-1 receptor agonists have demonstrated cardiovascular benefits by reducing the risk of major adverse cardiovascular events, enhancing their appeal for high-risk patients.
• Oral non-peptide glucagon-like peptide-1 receptor agonists exhibit a favorable side-effect profile with a lower risk of hypoglycemia compared to some other antidiabetic drugs, and they are generally well-tolerated, often causing mild and transient gastrointestinal side effects. This can improve the overall quality of life for patients.

Key Features of Oral Non-peptide GLP-1 RAs

Oral Administration

The most significant advantage of oral non-peptide GLP-1 RAs is their route of administration. Unlike traditional GLP-1 RAs, which require subcutaneous injections, these new agents can be taken orally, making them more convenient and patient-friendly. This feature addresses a longstanding barrier to medication adherence in diabetes management.

GLP-1 Receptor Activation

GLP-1 is a natural hormone that regulates glucose homeostasis by stimulating insulin secretion, suppressing glucagon release, and slowing gastric emptying. Oral non-peptide GLP-1 RAs mimic the actions of GLP-1, leading to improved blood sugar control.

Weight Management

Many patients with type 2 diabetes struggle with obesity or excess body weight. In the realm of diabetes care, it’s essential to address not just blood sugar levels but also associated health issues like obesity. GLP-1 RAs, including the oral non-peptide variants, are known for their potential to promote weight loss. This effect is particularly beneficial for individuals with both diabetes mellitus and obesity. Emphasizing a holistic approach in diabetes care, incorporating both blood sugar management and weight control, can lead to better overall health outcomes. As more healthcare professionals incorporate diabetes care strategies that tackle both conditions, patients can look forward to a more comprehensive and effective treatment plan.

Cardiovascular Benefits

Some oral non-peptide GLP-1 RAs have demonstrated cardiovascular benefits by reducing the risk of major adverse cardiovascular events. Notably, the hazard ratio for these drugs indicates a significant decrease in the likelihood of major cardiovascular events in patients using them. This cardiovascular protection extends to the oral formulations and contributes to their appeal in high-risk patients.

Fewer Side Effects

Oral non-peptide GLP-1 RAs exhibit a favorable side-effect profile, with a lower risk of hypoglycemia compared to some other antidiabetic medications. They are generally well-tolerated, and gastrointestinal side effects, if present, tend to be mild and transient.

Improved Quality of Life

The convenience of oral administration, combined with the overall effectiveness of non-peptide GLP-1 RAs in glycemic control and weight management, can significantly enhance a patient’s quality of life. Notably, a clinically significant difference in medication adherence may be observed when comparing oral to injectable treatments. This is particularly relevant for individuals with needle phobias or those averse to injections.

Combination Therapy

Oral non-peptide GLP-1 RAs can be used alone or in combination with other antidiabetic agents, offering flexibility in treatment regimens and the potential for personalized diabetes management.

Medications Under Oral Non-peptide Glucagon-like Peptide-1 Receptor Agonists (Small Molecule Agonists)

Other oral non-peptide GLP-1 RAs are currently in development. Some of the most promising oral non-peptide GLP-1 RAs include:

Danuglipron (PF-06882961)

Developed by Pfizer, danuglipron is an oral small-molecule GLP-1 receptor agonist that has been in clinical trials. It is designed to offer the therapeutic benefits of GLP-1 receptor stimulation, which includes enhancing insulin secretion in response to glucose, suppressing glucagon secretion, and reducing appetite. These effects are beneficial for the treatment of type 2 diabetes. Pfizer has likely published the results of early clinical trials, providing insights into the drug’s pharmacokinetics, pharmacodynamics, efficacy, and safety.

Orforglipron (LY3502970)

Orforglipron is an oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist currently under development for the treatment of type 2 diabetes and obesity. It works by mimicking the effects of GLP-1, a naturally occurring hormone that helps to regulate blood sugar levels and appetite. Orforglipron has demonstrated promising efficacy in clinical trials, showing significant reductions in HbA1c, body weight, and cardiometabolic risk factors. It is generally well-tolerated, with the most common side effects being gastrointestinal events. Orforglipron has the potential to be a valuable new treatment option for people with type 2 diabetes and obesity.

TT-OAD2

TT-OAD2 is a non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist with an EC50 of 5 nM. It has the potential for diabetes treatment. TT-OAD2 is a biased agonist, meaning it activates the GLP-1 receptor more strongly than other GLP-1 agonists. This may make it more effective in lowering blood sugar levels. TT-OAD2 is also more stable than other GLP-1 agonists, meaning it can be taken orally instead of being injected. This could make it a more convenient treatment option for people with diabetes. TT-OAD2 is still under development, but it has shown promising results in animal studies. It has been shown to lower blood sugar levels, improve insulin secretion, and reduce body weight. TT-OAD2 is also generally well-tolerated. The most common side effects are gastrointestinal problems, such as nausea and vomiting.

Lotiglipron

Lotiglipron, developed by Pfizer, is an oral non-peptide agonist of the glucagon-like peptide-1 receptor, initially researched as a medication for weight loss. In clinical trials, lotiglipron was shown to be effective in lowering blood sugar levels and body weight. However, it was also associated with an increased risk of elevated liver enzymes, which can be a sign of liver damage. As a result, Pfizer discontinued the development of lotiglipron in 2023.

Oral Non-peptide Glucagon-like Peptide-1 Receptor Agonists: Impact on Glycemic Control in Type 2 Diabetes

The evolution of diabetes treatment has witnessed the development of several therapeutic agents, among which glucagon-like peptide-1 (GLP-1) receptor agonists stand out due to their novel mechanism of action. These drugs, initially available only as injectables, have been increasingly gaining ground in the medical community. The advent of oral non-peptide GLP-1 receptor agonists has been seen as a promising breakthrough, primarily due to their ease of administration, which enhances patient compliance. Their pivotal role lies in their efficacy in maintaining glycemic control in individuals with type 2 diabetes.

The mechanism of action of GLP-1 receptor agonists is multifaceted. They enhance insulin secretion in a glucose-dependent manner, reduce inappropriate glucagon secretion, and slow gastric emptying, which collectively aids in achieving improved postprandial glucose control. When taken orally, these non-peptide GLP-1 receptor agonists efficiently mimic the actions of endogenous GLP-1, leading to better regulation of blood sugar levels. Clinical trials have demonstrated that oral formulations can significantly reduce hemoglobin A1c (HbA1c) levels, a key marker for long-term glucose control, in patients with type 2 diabetes.

One of the landmark studies on oral GLP-1 receptor agonists showcased their potential in achieving meaningful HbA1c reductions, often bringing patients to their target glycemic levels. This impact on glycemic control also came with the added benefit of weight loss in many patients, an advantage not commonly associated with many other antidiabetic drugs. The weight loss, coupled with improved glycemic control, presents a dual benefit, considering the high prevalence of obesity among individuals with type 2 diabetes.

Nevertheless, while the benefits of oral non-peptide GLP-1 receptor agonists are evident, it’s essential to tailor the therapy to individual patients. Some patients might experience gastrointestinal side effects, such as nausea or diarrhea, which can be transient but may impact medication adherence. Therefore, initiating therapy at a lower dose and gradually titrating based on individual response can optimize both tolerability and efficacy.

In conclusion, oral non-peptide GLP-1 receptor agonists represent a significant advancement in the management of type 2 diabetes. Their impact on glycemic control has proven beneficial in clinical settings, offering an effective and more patient-friendly alternative to injectable counterparts. As research progresses and more real-world data become available, these drugs could potentially reshape the landscape of diabetes care, offering hope to millions struggling with glycemic control.

Recent Updates on Oral Non-peptide Glucagon-like Peptide-1 Receptor Agonists

The New England Journal of Medicine has published Lilly’s Phase 2 trial results, demonstrating that Orforglipron, a daily, orally administered non-peptide GLP-1 receptor agonist, resulted in an average weight reduction of up to 14.7% at 36 weeks among adults who are overweight or obese

Last June 23, 2023, Eli Lilly and Company announced significant findings from the phase 2 study of orforglipron, a novel oral GLP-1 receptor agonist, targeting chronic weight management in individuals with obesity or overweight.

In the 26-week primary endpoint, orforglipron at doses of 12 mg, 24 mg, 36 mg, and 45 mg showed significant dose-dependent weight reductions ranging from 8.6% to 12.6% compared to 2.0% for placebo. This reduction continued at 36 weeks, with weight loss ranging from 9.4% to 14.7% across all doses, versus 2.3% for placebo.

The safety profile of orforglipron was consistent with other incretin-based therapies, with gastrointestinal side effects being the most common adverse events, typically mild-to-moderate and occurring mainly during the dose escalation phase.

At 36 weeks, all four doses of orforglipron achieved key secondary endpoints:

• Body weight reductions of ≥5% were observed in 72% to 92% of participants across doses compared to 24% with placebo.
• Body weight reductions of ≥10% were seen in 47% to 75% of participants versus 9% with placebo.
• BMI reduction from baseline was 3.4 kg/m2 to 5.5 kg/m2 across doses compared to 0.9 kg/m2 with placebo.
• Waist circumference reduction from baseline varied from 9.6 cm to 13.6 cm versus 4 cm with placebo.

An additional phase 2 study showed that orforglipron effectively reduced A1C and body weight in adults with type 2 diabetes, with a comparable safety profile to other GLP-1 receptor agonists.

These promising results have led Lilly to initiate phase 3 development programs (ATTAIN trials for obesity and overweight, ACHIEVE trials for type 2 diabetes) to further assess orforglipron’s efficacy and safety.

This study represents a significant advancement in potential oral treatments for chronic conditions like obesity and type 2 diabetes, offering hope for more diverse and accessible treatment options.

Pfizer halts development of investigational obesity drug amid concerns over increased liver enzymes

Pfizer announced on June 26, 2023, its decision to discontinue the development of its experimental pill, lotiglipron, for obesity and diabetes, following observations of elevated liver enzymes in patients from midstage clinical trials. Although no liver-related symptoms or side effects were reported, the rise in enzymes often suggests potential liver cell damage.

Despite this setback, which led to a 3.6% drop in Pfizer’s shares, the New York-based company is redirecting its focus towards another oral obesity drug, danuglipron, currently undergoing a fully enrolled phase two clinical trial. Preliminary results indicated significant body weight reduction in type 2 diabetes patients after 16 weeks of high-dose danuglipron administered twice daily. Pfizer aims to finalize plans for a phase three trial of danuglipron by the end of 2023 and is also working on a once-daily version of the drug.

William Sessa, Pfizer’s Chief Scientific Officer of Internal Medicine, expressed optimism about advancing danuglipron’s development, targeting optimal dosing and safety. Pfizer CEO Albert Bourla has projected that an effective obesity pill could potentially generate annual revenue of $10 billion.

Lotiglipron, danuglipron, and Novo Nordisk’s successful weight loss injections, Ozempic and Wegovy, belong to the glucagon-like peptide-1 agonists class. These drugs imitate the GLP-1 hormone, signaling satiety to the brain and stimulating insulin release to lower blood sugar, making them beneficial for type 2 diabetes management.

The prospect of oral drugs like danuglipron, which offers an alternative to frequent injections, is creating significant interest in the weight loss industry. Novo Nordisk and Eli Lilly are also developing their oral obesity and diabetes medications.

However, challenges remain regarding these drugs’ accessibility and long-term usage implications, especially considering the potential for weight regain after discontinuation. With over 40% of adults in the United States battling obesity and about 9% facing severe obesity, the demand for effective treatments is high.

Analysts currently view Eli Lilly’s orforglipron as a strong competitor in the oral weight loss drug market. According to Wells Fargo analyst Mohit Bansal, orforglipron, taken once daily, has shown promising results, with patients losing 14.7% of their body weight over 36 weeks in midstage trials. This efficacy, combined with the convenience of a once-daily regimen, positions orforglipron as a formidable benchmark for danuglipron and other competitors in the field.

Pfizer announces GLP-1-RA clinical development update: Proceeding with danuglipron trials for obesity and type 2 diabetes mellitus, discontinuing lotiglipron

Pfizer Inc. announced on June 26, 2023, its strategic decision to focus on advancing danuglipron (PF-06882961), a promising oral late-stage glucagon-like peptide-1 receptor agonist (GLP-1-RA), in its clinical development pipeline for treating adults with obesity and type 2 diabetes mellitus (T2DM). This decision follows the results from the ongoing Phase 2 trial and involves discontinuing the development of another candidate, lotiglipron (PF-07081532). Plans to finalize the late-stage program for danuglipron are expected by the end of 2023, along with the development of a once-daily modified-release version.

William Sessa, Ph.D., Senior Vice President and Chief Scientific Officer of Internal Medicine at Pfizer, commented on the company’s direction, noting their expertise in small molecule design and their goal to optimize danuglipron’s dosage for maximum therapeutic benefits, safety, and tolerability. Danuglipron has demonstrated potential in clinical trials with its full receptor agonism, which could translate into robust efficacy if successful.

The Phase 2 study (NCT03985293) of danuglipron in T2DM, published in the Journal of the American Medical Association Network Open, showed dose-dependent reductions in HbA1c, fasting plasma glucose, and body weight over 16 weeks, with the most common adverse events being gastrointestinal in nature. The ongoing Phase 2b study in non-diabetic obese participants (doses up to 200 mg for 32 weeks) is set to conclude by year-end, showcasing a safety profile consistent with peptidic GLP-1R agonists.

The discontinuation of lotiglipron is based on Phase 1 drug-drug interaction studies and observations of elevated transaminases without any reported liver-related symptoms or evidence of liver failure. These findings from the lotiglipron studies will be shared at scientific conferences or in peer-reviewed journals. Unlike lotiglipron, danuglipron has not shown transaminase elevations in over 1,400 patients enrolled in its program.

GLP 1 Agonist Mechanism of Action

IMG

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represent a class of medications pivotal in the treatment of type 2 diabetes. By emulating the action of the naturally occurring hormone GLP-1, which is integral to blood sugar regulation and appetite control, these agents help manage glycemia and can aid in weight reduction. Their efficacy and safety profiles have been extensively studied in randomized clinical trials, revealing that GLP-1 RAs operate through several mechanisms: they stimulate insulin secretion in a glucose-dependent manner, suppress inappropriately elevated glucagon secretion, and slow gastric emptying, thereby modulating blood glucose levels post-meals. Additionally, they act on the brain to increase satiety, which contributes to their weight-reducing effects.

Stimulation of Insulin Secretion

GLP-1 receptor agonists stimulate the pancreas to release insulin in a glucose-dependent manner. This means that they increase insulin secretion when blood sugar levels are elevated, such as after a meal. Insulin helps move glucose from the bloodstream into cells, where it can be used for energy or stored for later use.

Inhibition of Glucagon Release

GLP-1 receptor agonists suppress the release of glucagon, another hormone produced by the pancreas. Glucagon raises blood sugar levels by prompting the liver to release glucose into the bloodstream. Inhibiting glucagon helps reduce excess glucose production in the liver.

Slowing of Gastric Emptying

GLP-1 receptor agonists delay the emptying of the stomach contents into the small intestine. This slows the absorption of glucose from the digestive tract into the bloodstream, leading to more stable post-meal blood sugar levels.

Appetite Regulation

GLP-1 receptor agonists act on the brain to reduce appetite and increase feelings of fullness (satiety). This effect can lead to reduced food intake and, consequently, weight loss in some individuals.

Beta-Cell Protection

There is evidence to suggest that GLP-1 receptor agonists may have a protective effect on pancreatic beta cells, which are responsible for producing insulin. This protection may help preserve beta-cell function over time.

Weight Loss

Many GLP-1 receptor agonists are associated with weight loss in people with type 2 diabetes. This effect is partly due to reduced appetite and food intake, as well as potential changes in how the body stores fat.

Cardiovascular Benefits

Some GLP-1 receptor agonists have demonstrated cardiovascular benefits, including a reduced risk of major adverse cardiovascular events in clinical trials. These benefits may be related to their effects on blood sugar, blood pressure, and other cardiovascular risk factors.

It’s important to note that GLP-1 receptor agonists are typically administered as injections, although there is ongoing research into the development of oral GLP-1 receptor agonists. These medications are often used in combination with other diabetes medications, such as metformin, to achieve better blood sugar control.

The specific mechanisms of action can vary among different GLP-1 receptor agonists, as there are several drugs in this class with slightly different properties. Your healthcare provider can help determine which GLP-1 RA is most appropriate for your individual needs and medical history.

GLP 1 Agonist Drugs

GLP-1 agonist drugs and GLP-1 receptor agonists refer to the same class of medications. “GLP-1” stands for “glucagon-like peptide-1,” and these drugs are designed to mimic the action of endogenous GLP-1 by binding to and activating GLP-1 receptors in the body. These medications are used in the treatment of type 2 diabetes to help regulate blood sugar levels and may also have other benefits, such as promoting weight loss.

Here is a complete list of GLP-1 agonist drugs, both injectable and oral, with important information about each drug:

Injectable GLP-1 agonists:

Albiglutide (Tanzeum)

Albiglutide, marketed under the name Tanzeum, is a notable once-weekly injectable GLP-1 receptor agonist that has gained approval for managing type 2 diabetes. As a GLP-1 receptor agonist, it works by mimicking the functions of the body’s native GLP-1, which is involved in glucose regulation and appetite suppression. Beyond its diabetes indication, albiglutide has also received approval for treating obesity in adults whose body mass index (BMI) stands at 30 kg/m^2 or higher, or 27 kg/m^2 or higher if accompanied by at least one weight-related medical condition. This dual-purpose medication offers a convenient and comprehensive approach to address both glycemic control and weight management in eligible patients, potentially improving their overall health outcomes.

Dulaglutide (Trulicity)

Dulaglutide, marketed under the brand name Trulicity, is a notable once-weekly injectable medication belonging to the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). As a GLP-1 receptor agonist, it mimics the actions of the body’s native glucagon-like peptide-1, leading to increased insulin release and reduced glucose production. Primarily approved for the management of type 2 diabetes, it has demonstrated remarkable efficacy in regulating blood sugar levels. Additionally, its role as a GLP-1 receptor agonist also contributes to its efficacy in addressing obesity concerns in adults, especially those with a BMI of 30 kg/m2 or higher, or with a BMI of 27 kg/m2 or higher coupled with at least one weight-related medical condition. This dual-purpose medication not only aids in glycemic control but also offers a potential solution for individuals seeking to manage their weight. Its convenient weekly dosing schedule makes it an attractive option for those looking for an effective, less frequent injection-based therapy.

Exenatide (Byetta, Bydureon)

Exenatide-extended release, which is also referred to as Bydureon, is a version of exenatide that needs less frequent dosing than the original Byetta formulation. Exenatide, available as Byetta or Bydureon, is a twice-daily injectable glucagon-like peptide 1 (GLP-1) receptor agonist that has gained approval for the management of type 2 diabetes. Another formulation, exenatide extended-release, offers patients the convenience of once-weekly dosing. This GLP-1 receptor agonist medication has also received authorization for use in addressing obesity concerns among adults.

To qualify for obesity treatment with this GLP-1 receptor agonist, individuals should have a BMI of 30 kg/m² or higher, or a BMI of 27 kg/m² or higher while presenting with at least one weight-related medical condition. Exenatide extended-release, much like its counterpart, operates by mimicking the effects of GLP-1, enhancing insulin secretion and moderating glucagon release in response to glucose levels. This dual-action mechanism aids in controlling blood sugar after meals, which is particularly beneficial for those with type 2 diabetes. Moreover, the exenatide extended-release formulation has shown promise in supporting weight loss efforts in individuals grappling with obesity, making it a valuable option in the treatment landscape for both conditions.

Liraglutide (Victoza, Saxenda)

Liraglutide, marketed under the brand names Victoza and Saxenda, is a highly versatile medication with dual therapeutic indications. As an injectable glucagon-like peptide 1 (GLP-1) receptor agonist, it is primarily approved for the management of type 2 diabetes, offering a once-daily dosing regimen. The mechanism of action involves its role as a GLP-1 receptor agonist, which aids in controlling blood sugar levels by promoting insulin secretion when glucose is present in the blood. Beyond its role in diabetes care, Liraglutide is also recognized as an effective treatment option for obesity in adults. Specifically, it is indicated for individuals with a BMI (Body Mass Index) of 30 kg/m² or higher, or those with a BMI of 27 kg/m² or higher who have at least one weight-related medical condition. The effectiveness of Liraglutide in weight management can be attributed to its properties as a GLP-1 receptor agonist, which also suppresses appetite and delays gastric emptying. This dual-action medication has been widely embraced by healthcare professionals as it addresses both diabetes and obesity, offering the potential for improved glycemic control and weight management in eligible patients.

Lixisenatide (Adlyxin)

Lixisenatide, marketed under the brand name Adlyxin, is a once-daily injectable glucagon-like peptide-1 (GLP-1) receptor agonist designed to address the needs of individuals with type 2 diabetes. It functions by activating GLP-1 receptors, which helps stimulate insulin secretion in response to elevated blood sugar levels while inhibiting glucagon release. These actions promote glucose control, particularly after meals, making it an effective addition to diabetes management regimens. Lixisenatide’s extended duration of action provides sustained glycemic control throughout the day, reducing the risk of hyperglycemia. Moreover, it has demonstrated benefits in terms of weight management, as GLP-1 receptor agonists are known to suppress appetite and support weight loss in some patients. Typically administered via subcutaneous injection, lixisenatide offers a valuable treatment option for those requiring additional glycemic control beyond oral medications or other injectable therapies.

Semaglutide (Ozempic, Wegovy)

Semaglutide, available under the brand names Ozempic and Wegovy, is a significant advancement in diabetes and obesity management. This once-weekly injectable glucagon-like peptide 1 (GLP-1) receptor agonist has received approval not only for treating type 2 diabetes but also for addressing obesity concerns in adults. For diabetes management, semaglutide aids in regulating blood sugar levels by stimulating insulin release and inhibiting glucagon secretion, helping individuals achieve better glycemic control. Additionally, it offers a promising solution for those struggling with obesity, particularly in adults with a BMI of 30 kg/m² or higher, or 27 kg/m² or higher with at least one obesity-related medical condition. By promoting weight loss, semaglutide proves to be a versatile therapeutic option in addressing two major health challenges—type 2 diabetes and obesity—enhancing the overall well-being of patients.

Oral GLP-1 agonists:

Semaglutide (Rybelsus)

Semaglutide is a once-daily oral tablet that is approved for the treatment of type 2 diabetes. It is a groundbreaking medication in the field of diabetes management, belonging to the class of oral non-peptide glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Unlike traditional GLP-1 RAs, which are administered by injection, this oral non-peptide glucagon-like peptide 1 receptor agonist comes in a tablet form. Its mechanism of action involves activating GLP-1 receptors in the body, similar to natural GLP-1, thereby stimulating insulin secretion and inhibiting glucagon release in a glucose-dependent manner. This effect helps regulate blood sugar levels after meals.

Additionally, oral semaglutide has been found to slow gastric emptying, reduce appetite, and promote weight loss in individuals with type 2 diabetes. The convenience of an oral tablet makes it a promising option for those who prefer non-invasive treatment methods, potentially improving adherence to therapy and overall glycemic control in people living with diabetes.

GLP 1 receptor agonists are generally well-tolerated, with the most common side effects being mild and digestive in nature. Some of the most common side effects of GLP-1 agonists include nausea, vomiting, diarrhea, and stomach upset. These side effects are usually mild and go away on their own within a few days.

GLP-1 agonists can also cause low blood sugar levels, especially in people who are also taking other diabetes medications such as insulin or sulfonylureas. It is important to monitor your blood sugar levels closely when taking GLP-1 agonists.

GLP-1 agonists are a very effective class of drugs for lowering blood sugar levels and promoting weight loss. They are also generally well-tolerated, with the most common side effects being mild and digestive in nature.

If you are interested in learning more about GLP-1 agonists, talk to your doctor.

Non-peptidyl Oral Glucagon-like Peptide-1 Receptor Agonists vs Glucagon-like Peptide-1 Receptor Agonists

Non-peptidyl oral glucagon-like peptide-1 receptor agonists offer several advantages over traditional injectable GLP-1 receptor agonists (GLP-1 RAs) in the treatment of type 2 diabetes. In the realm of evaluating treatment efficacy and comparing diverse treatment options, mixed treatment comparison is an essential tool. By using mixed treatment comparison, healthcare professionals can gain deeper insights into how these medications stand against other therapies, both in terms of efficacy and side effects. Such comparisons are vital to making informed decisions about the most appropriate treatment choices for patients:

• Ease of Administration: One of the most significant advantages of non-peptidyl oral GLP-1 RAs is their oral route of administration. Patients can take these medications in tablet form, eliminating the need for injections, which can be uncomfortable and inconvenient.
• Improved Adherence: Oral medications are generally more convenient for patients to incorporate into their daily routines. Improved adherence to treatment plans can lead to better glycemic control and health outcomes.
• Reduced Fear of Needles: Many people have a fear of needles or injections, which can lead to injection-related anxiety or avoidance. Non-peptidyl oral GLP 1 receptor agonists can alleviate this fear, making treatment more accessible to a broader range of patients.
• Potential for Earlier Intervention: The availability of an oral GLP-1 RA may encourage healthcare providers to consider treatment with GLP-1 receptor agonists earlier in the disease management process. Early intervention can help control blood sugar levels and slow disease progression.
• Increased Patient Acceptance: Some individuals may be hesitant to start injectable medications due to the perceived inconvenience or discomfort. Non-peptidyl oral GLP 1 receptor agonist options may be more acceptable to these patients, increasing the likelihood that they will initiate and adhere to treatment.
• Broader Patient Population: The ease of oral administration may make GLP-1 RA therapy accessible to a broader population, including those who may have reservations about injections or have difficulty self-administering injections.
• Potential for Combination Therapy: Oral GLP 1 receptor agonists can be more easily combined with other oral antidiabetic medications, simplifying treatment regimens for patients who require multiple medications to manage their diabetes effectively.
• Reduced Injection Site Reactions: Traditional injectable GLP 1 receptor agonists can sometimes cause injection site reactions, including redness, swelling, or discomfort. Oral medications eliminate the risk of such reactions.
• Patient Preference: Patients often prefer oral medications over injectable ones, and this preference can positively impact treatment compliance and overall satisfaction with therapy.
• Improved Quality of Life: The convenience of oral GLP 1 receptor agonists can contribute to an improved quality of life for individuals with type 2 diabetes, as it simplifies their treatment regimen.
• Easier Dosing: With oral medications, patients can easily take their prescribed dose without the need for specialized equipment or training.
• Privacy: Some patients appreciate the privacy of taking oral medications without the need for visible injections, especially in social or work settings.
• Lower Risk of Needlestick Injuries: Healthcare providers and caregivers face a lower risk of accidental needlestick injuries when managing patients on oral GLP 1 receptor agonists.

It’s important to note that while non-peptidyl oral GLP-1 RAs offer these advantages, they also have their own set of considerations and potential side effects. Patients should work closely with healthcare providers to determine the most appropriate treatment based on their individual needs and medical history. Additionally, not all GLP-1 RAs are available in oral form, so medication choices may vary.