Beyond Ozempic: A Look at GLP-1 Medications

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Glucagon-like peptide-1 receptor agonist drugs -- GLP-1s -- are a class of medications primarily used for the management and treatment of type 2 diabetes. Recently, they’ve become increasingly popular for weight loss. These medications mimic the action of the naturally occurring GLP-1 hormone, which plays a crucial role in regulating blood sugar levels and appetite. GLP-1s, which include the best-known Ozempic® (semaglutide), have revolutionized diabetes treatment by effectively regulating blood sugar levels, promoting weight loss, and even benefiting cardiovascular health.

GLP-1 receptor agonists are also being increasingly prescribed for weight loss and management. And Ozempic® isn’t the only GLP-1 medication available. This article looks at what you need to know about the full range of GLP-1 medications on the market, including brand names, their generic versions, and compounded GLP-1 treatments.

GLP-1 receptor agonists mimic the GLP-1 hormone, which is naturally produced in your body. This hormone helps regulate blood sugar by increasing insulin release after eating, slowing down gastric emptying (delaying food leaving the stomach), and signaling feelings of fullness (known as satiety) in your brain. These effects make GLP-1 agonists highly beneficial not only for managing blood sugar but also for supporting weight loss.

These combined effects improve blood sugar control and often lead to significant weight loss, making GLP-1s among modern medicine’s most valuable tools in managing type 2 diabetes and obesity.

As research continues to uncover new potential applications, GLP-1 drugs are showing promise in addressing various health conditions and improving overall well-being.

Metabolic and cardiovascular benefits

GLP-1s have demonstrated significant cardiovascular benefits, particularly in patients with type 2 diabetes who are at higher risk for cardiovascular events. Clinical trials have shown that these medications can reduce the risk of major adverse cardiovascular events, including non-fatal stroke, myocardial infarction, and cardiovascular mortality.

Semaglutide and liraglutide, two prominent GLP-1s, have been particularly effective in reducing cardiovascular events. Research has shown that these drugs have similar rates of cardiovascular mortality reduction, making them valuable options for managing cardiovascular risk in diabetic patients.

Beyond their effects on major cardiovascular events, GLP-1s have also demonstrated the ability to:

• Lower blood pressure
• Reduce body weight
• Improve dyslipidemia (high cholesterol levels and abnormal levels of lipids or fats
• Enhance endothelial function (the many physiological functions of the endothelium, which is a single layer of cells that lines the inside of blood vessels and helps regulate blood pressure, blood flow, and other aspects of vascular health)

These effects contribute to overall cardiovascular health and may help prevent the development of atherosclerosis and other cardiovascular complications.

While all GLP-1s effectively reduce HbA1c levels, long-acting weekly GLP-1s like semaglutide and dulaglutide tend to be more effective in reducing fasting glucose and HbA1c levels compared to shorter-acting medications used daily.

All GLP-1s promote weight loss, but semaglutide (particularly at higher doses used for weight loss) and tirzepatide have demonstrated the most significant weight loss effects.

Tirzepatide has shown superior glycemic control compared to other GLP-1s, likely due to its dual action on GIP and GLP-1 receptors.

Kidney health protection

GLP-1s have shown promising results in protecting kidney function, especially in patients with type 2 diabetes and chronic kidney disease. A clinical trial called FLOW demonstrated that semaglutide reduced the risk of major kidney disease events by 24% compared to placebo. This included a lower likelihood of requiring dialysis, kidney transplant, or experiencing kidney-related death.

The protective effects of GLP-1s on the kidneys are thought to be mediated through both direct and indirect mechanisms. These drugs may reduce inflammation and fibrosis in the kidneys and improve overall metabolic health, which in turn benefits kidney function.

Neuroprotective effects

Emerging research suggests that GLP-1s may have significant neuroprotective properties, potentially benefiting brain health and cognitive function. These drugs appear to reduce inflammation in the brain and strengthen the blood-brain barrier, which could have implications for various neurological conditions.

Some of the potential neurological benefits of GLP-1s include:

• Reduced risk of neurodegenerative diseases like Alzheimer’s and Parkinson’s
• Improved cognitive function
• Potential treatment for multiple sclerosis and epilepsy

Studies have shown that GLP-1s can increase the number of astrocytes, which help protect the brain and maintain the blood-brain barrier. Additionally, these drugs may help reverse inflammation, potentially slowing or preventing neurodegeneration.

Addiction and behavioral health

An unexpected benefit of GLP-1s has been their potential impact on addiction and compulsive behaviors. While research is still in its early stages, there is growing evidence that these medications may help reduce alcohol consumption and potentially aid in treating other forms of addiction.

Patients taking GLP-1s have reported reduced cravings for alcohol and a lower tolerance to its effects. Some studies suggest that these drugs may interact with brain pathways related to pleasure and reward, potentially explaining their impact on addictive behaviors.

Furthermore, there are indications that GLP-1s may help reduce compulsive eating behaviors and the persistent thoughts about food that many individuals with obesity experience. This “quieting of food noise” could significantly benefit those struggling with weight management.

Gastrointestinal and liver effects

GLP-1s have shown promise in addressing gastrointestinal and liver-related conditions. These medications can reduce inflammation in both the small and large intestines, which may have implications for various digestive disorders.

In the liver, GLP-1s may help reduce inflammation and potentially lower the risk of metabolic liver diseases. This could be particularly beneficial for patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), conditions that are often associated with obesity and type 2 diabetes.

Anti-inflammatory effects

A common thread running through many of the health benefits of GLP-1s is their anti-inflammatory action. These drugs appear to have both direct and indirect anti-inflammatory effects throughout the body, which may explain their wide-ranging health benefits.

The anti-inflammatory properties of GLP-1s may contribute to their cardiovascular, renal, and neuroprotective effects. By reducing systemic inflammation, these medications may help prevent or slow the progression of various chronic diseases associated with inflammatory processes.

Cardiovascular effects

Beyond blood sugar management and weight loss, GLP-1 receptor agonists have gained recognition for their cardiovascular benefits and ability to significantly reduce cardiovascular risk reduction in people with type 2 diabetes. This makes GLP-1s particularly valuable for patients with type 2 diabetes who are also at high risk for heart disease. For example:

• Semaglutide (Ozempic®) is FDA-approved to reduce the risk of major adverse cardiovascular events in type 2 diabetes patients with established cardiovascular disease.
• Dulaglutide (Trulicity®) is approved for cardiovascular risk reduction in type 2 diabetes patients with or without established cardiovascular disease.
• Liraglutide (Victoza®) has also shown cardiovascular benefits in clinical trials.

Here’s a comprehensive list of brand name and generic GLP-1 receptor agonists, their indications, dosing schedules, and how they differ in their formulation, effectiveness, and side effects.

Semaglutide (Ozempic®, Wegovy®, Rybelsus®)

Semaglutide is one of the most potent GLP-1s, demonstrating significant efficacy in reducing blood sugar and HbA1c levels and promoting weight loss. Semaglutide is commonly prescribed at different doses based on patient needs and is among the most researched and effective GLP-1 drugs.

Semaglutide is available in both injectable and oral forms:

• Ozempic® (injection for type 2 diabetes)
• Wegovy® (injection for weight loss)
• Rybelsus® (daily oral tablet for type 2 diabetes)

While semaglutide drugs are approved for use in people with type 2 diabetes, Wegovy® is approved specifically for weight management in individuals with obesity or overweight conditions. Wegovy®, a higher-dose version of semaglutide, is tailored specifically for weight management. The FDA approval of Wegovy® marked a significant shift, showing semaglutide’s effectiveness in treating obesity.

The oral form of semaglutide effectively reduces blood sugar levels, but weight loss may be less pronounced than injectable forms.

Dulaglutide (Trulicity®)

Trulicity has been a popular choice for diabetes management due to its once-weekly dosing by injection, effectiveness for blood sugar control and moderate weight loss, and benefits for cardiovascular health. However, weight loss may not be as pronounced as with higher-dose semaglutide options like Wegovy®.

Exenatide (Byetta®, Bydureon®)

Exenatide was the first GLP-1 approved for clinical use. Exenatide is considered effective for blood sugar control but less effective for weight loss.

Byetta is administered with a twice-daily injection, and Bydureon – an extended-release form of exenatide -- is administered with a once-weekly injection.

Liraglutide (Victoza®, Saxenda®)

Liraglutide was one of the first long-acting GLP-1s and has been widely used for over a decade. It’s been a trusted drug for years, primarily for diabetes and heart health. Due to its daily administration by injection, it’s less convenient than weekly options but remains effective for blood sugar and weight control.

Victoza® is the brand name approved for type 2 diabetes, and Saxenda is a higher dose form approved for weight loss.

Tirzepatide: dual GIP/GLP-1 (Mounjaro®, Zepbound®)

Tirzepatide, marketed under the brand names Mounjaro® and Zepbound®, is a dual GIP and GLP-1 receptor agonist, representing a new class of diabetes medications. It offers a unique mechanism of action that sets it apart from other medications in its class.

A GIP receptor agonist is a type of medication that activates and stimulates the glucose-dependent insulinotropic polypeptide (GIP) receptor. GIP is a hormone produced in the gastrointestinal tract and belongs to a class of hormones called incretins. A GIP receptor agonist medication works by:

• Stimulating insulin secretion: They enhance the release of insulin from pancreatic beta cells in a glucose-dependent manner.
• Increasing insulin sensitivity: These agonists can improve the body’s responsiveness to insulin.
• Affecting appetite and satiety: GIP receptors in the central nervous system influence hunger and fullness signals.
• Slowing gastric emptying: They can reduce the rate at which food leaves the stomach, promoting a feeling of fullness.
• Influencing fat metabolism: GIP plays a role in lipid metabolism and fat deposition.

A dual agonist medication like tirzepatide acts as both a GIP and GLP-1 receptor agonist, potentially offering enhanced benefits for diabetes and weight management.

Zepbound®, the formulation of tirzepatide approved for weight loss, has shown significant success in clinical trials. In a 72-week study, patients taking the highest dose (15 mg) lost an average of 20.9% of their body weight, equivalent to about 48 pounds. This significant weight reduction was accompanied by improvements in various health markers, including waist circumference, blood pressure, and cholesterol levels.

The medication is administered as a once-weekly subcutaneous injection, with doses ranging from 2.5 mg to 15 mg. It’s indicated for adults with obesity (BMI ≥ 30 kg/m²) or overweight individuals (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

While Zepbound® is approved for weight management, Mounjaro® contains the same active ingredient but is FDA-approved for type 2 diabetes treatment. Both medications have shown promise in improving glycemic control and aiding in weight loss.

Compounded GLP-1 medications

As demand for these medications surges, some patients and healthcare providers have turned to compounded versions of GLP-1 drugs. Compounded GLP-1 drugs are versions of GLP-1 medications created by compounding pharmacies rather than manufactured by pharmaceutical companies.

One of the primary advantages of compounded GLP-1 drugs is improved accessibility. With shortages of FDA-approved GLP-1 medications like Ozempic® and Wegovy®, compounded versions can help ensure continuity of care for patients already on these medications. This is particularly important given the dosing schedule and potential side effects associated with starting and stopping GLP-1 drugs.

Another advantage is the cost. Compounded GLP-1 medications are usually significantly less expensive than brand-name medications. Compounded versions can provide a more affordable option for patients without insurance coverage or those facing high out-of-pocket costs. Many compounding pharmacies offer these medications at substantial discounts compared to the list prices of brand-name drugs.

Compounding also allows for customization of medications to meet your needs. This can include adjusting dosages, combining multiple medications, or creating alternative formulations if you have allergies or sensitivities to certain ingredients.

The most commonly compounded GLP-1 drugs are semaglutide and tirzepatide.

Remember that when considering compounded GLP-1 medications, you’ll want to ensure that your compounded medication is obtained from a reputable, licensed compounding pharmacy recommended by your healthcare provider.

While all GLP-1s share a common mechanism of action, they differ in several essential aspects, including how often you take them, and in what form. 

Dosing frequency

GLP-1s vary in their dosing frequency, which can significantly impact patient adherence and preference:

• Twice-daily: Exenatide (Byetta)
• Once-daily: Liraglutide (Victoza®, Saxenda), Semaglutide tablets (Rybelsus®)
• Once-weekly: Semaglutide (Ozempic®, Wegovy®), Dulaglutide (Trulicity), Exenatide extended-release (Bydureon), Tirzepatide (Mounjaro®, Zepbound®)

The once-weekly formulations generally offer greater convenience and may improve adherence.

Formulations/administration route

Most GLP-1s are administered via subcutaneous (under the skin) injection. However, semaglutide (Rybelsus®) is available as an oral tablet, offering an option for patients who prefer to avoid injections. However, oral semaglutide offers less consistent and noticeable results in terms of blood sugar control and weight loss.

While GLP-1 drugs offer significant benefits, your provider and you should also be aware that these medications come with potential side effects and adverse reactions.

• Nausea and vomiting: Nausea is the most frequently reported side effect, affecting up to 50% of patients taking GLP-1 drugs. Most cases are mild to moderate and tend to diminish over time as the body adjusts to the medication. Vomiting is less common but still affects a significant number of patients. For example, dulaglutide at a 1.5 mg dose was associated with a 17% incidence of vomiting compared to 12% with exenatide.
• Diarrhea and constipation: Both diarrhea and constipation are common side effects of GLP-1 agonists. The prevalence varies between different drugs in the class, but these symptoms are generally reported as common.
• Abdominal pain and indigestion: Abdominal pain and indigestion are also relatively common side effects. These symptoms are usually mild to moderate and often improve with time.
• Injection site reactions: For GLP-1 agonists administered via injection, local reactions at the injection site are common. These can include itching, redness, swelling, and bruising. Most injection site reactions are mild and resolve on their own. Rotating injection sites and proper injection techniques can help minimize these reactions.

Most adverse effects associated with GLP-1 agonists are mild to moderate and often improve with time. To reduce the risk of side effects and any adverse events from GLP-1 medications, here are some guidelines to keep in mind:

• Start with a low dose and gradually increase the dose over time
• Take the medication with meals
• Eat smaller, more frequent meals
• Stay well-hydrated
• Avoid fatty, spicy, or smelly foods if they exacerbate symptoms
• Consider anti-nausea medications if needed
• For constipation: Use fiber-rich foods (and over-the-counter laxatives) if needed for constipation
• Use proper injection technique and rotate injection sites
• Monitor blood glucose levels regularly, especially if taking other diabetes medications

Allergic reactions

Although rare, allergic reactions to GLP-1 agonists can occur. These can range from mild skin reactions to severe anaphylaxis. Patients should be aware of the signs of a severe allergic reaction and seek immediate medical attention if they occur.

Hypoglycemia 

GLP-1 agonists themselves have a low risk of causing hypoglycemic episodes. The risk of hypoglycemia (low blood sugar) increases when they are combined with other glucose-lowering medications, particularly sulfonylureas or insulin. Patients should be educated about the symptoms of low blood glucose levels and how to manage them.

Pancreatitis

There has been ongoing debate about the risk of pancreatitis with GLP-1 agonists. While some studies have suggested an increased risk, others have found no significant association. A pooled analysis of clinical trials showed a slightly elevated but not statistically significant risk. Patients should be aware of the symptoms of pancreatitis, which include severe abdominal pain, and seek immediate medical attention if they occur.

Intestinal obstruction

Recent reports have led to the FDA updating labeling for some GLP-1 agonists, including Ozempic®, to include a warning about intestinal blockage (ileus). Patients should be aware of symptoms such as severe abdominal pain, an inability to pass gas, or difficulty moving bowels and seek immediate medical attention if these occur.

Gastroparesis

Gastroparesis, or delayed gastric emptying, has been reported in some patients taking GLP-1 agonists. This condition can lead to persistent nausea, vomiting, and abdominal discomfort.

Thyroid effects

Studies have shown an increased risk of thyroid C-cell tumors with some GLP-1 agonists. For this reason, GLP-1 medications are not recommended if you have a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2.

Pregnancy and breastfeeding

GLP-1 medications are not recommended during pregnancy or breastfeeding. Animal studies have shown potential risks to fetal development, and there is insufficient data on their safety in human pregnancy.

The choice of GLP-1 should be individualized based on several factors:

• Your treatment goals: Consider whether the primary aim is controlling blood glucose levels, weight loss, or reducing cardiovascular risk.
• Your preference: Factors such as dosing frequency and injectible versus oral forms can influence your adherence and satisfaction.
• Other health conditions: The presence of cardiovascular disease, kidney problems, or other conditions may influence the choice of GLP-1.
• Tolerability: While all GLP-1s can cause gastrointestinal side effects, your tolerance may vary depending on the drug you’re taking.
• Cost and insurance coverage: The availability and cost of different GLP-1s can vary significantly depending on your insurance coverage and geographical location.

For people with Hashimoto’s or hypothyroidism, GLP-1 drugs may offer direct benefits, especially in weight management, metabolic health, reducing inflammation, and improving some symptoms of hypothyroidism:

Weight loss

Many people with hypothyroidism or Hashimoto’s struggle with weight gain due to a slowed metabolism. GLP-1 drugs work by promoting feelings of fullness and reducing appetite, which can help in losing weight. Managing weight can also improve thyroid function indirectly since excess body fat can exacerbate inflammation and hormonal imbalances.

Improved metabolic health

Hypothyroidism often increases the risk of insulin resistance and metabolic syndrome, as well as the risk of pre-diabetes and type 2 diabetes. GLP-1 drugs can improve blood sugar regulation, which is beneficial for insulin sensitivity. This can help stabilize your energy levels, reduce cravings, and improve overall metabolic health, potentially offsetting some of the challenges linked to your underactive thyroid.

Reduced inflammation

Chronic inflammation is a feature of Hashimoto’s, and studies have shown that GLP-1 drugs may reduce markers of inflammation. Lowering inflammation can help alleviate some symptoms, such as fatigue and joint pain, and may slow down the progression of autoimmune thyroid damage.

Gut health benefits

GLP-1 drugs may support gut health by slowing gastric emptying, which can help in cases of irritable bowel syndrome (IBS)-like symptoms often found in people with hypothyroidism. Better gut health can also improve nutrient absorption, which is essential for optimal thyroid health.

GLP-1 receptor agonists are a promising treatment option for managing type 2 diabetes and supporting weight loss, but not all options are suitable for everyone. Different GLP-1 medications have unique attributes, including dosing schedules, side effect profiles, and specific indications. Understanding these distinctions allows you to make informed choices that align with your unique health needs and goals.

While GLP-1 medications offer potential health benefits, their long-term effects remain an area of active study. Researchers continue investigating these medications to uncover their broader applications and the full scope of side effects over extended use. As knowledge expands, GLP-1s may serve roles beyond diabetes and weight management, potentially becoming useful in treating various metabolic and health conditions. Staying updated on the latest findings can be crucial for patients seeking these medications, especially those managing complex conditions like hypothyroidism or Hashimoto’s.

If you’re considering GLP-1 treatment as part of your weight or metabolic health strategy with hypothyroidism or Hashimoto’s, being a Paloma Health member can provide you with the essential support you need. Paloma’s specialized care in thyroid health can help determine whether GLP-1 medications are appropriate for you. With a focus on integrative care, Paloma Health can help you navigate the intricacies of GLP-1 therapy while optimizing your thyroid management.

As with any treatment, deciding to use a GLP-1 agonist should involve a thorough consultation with your healthcare providers to weigh the benefits against potential risks. Working with the dedicated healthcare providers at Paloma Health ensures you will get ongoing support, regular monitoring, and open communication to safely maximize the benefits of GLP-1 medications. You can feel confident that your care plan considers all aspects of your health, with Paloma Health’s expertise offering a tailored approach to both thyroid and metabolic wellness.

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*Compounded semaglutide is not approved or evaluated for safety, efficacy, or quality by the FDA. Wegovy® (semaglutide) and Ozempic ® (semaglutide) are not compounded. Wegovy® (semaglutide) is FDA-approved for weight loss. Ozempic® (semaglutide) is FDA-approved for type 2 diabetes but may be prescribed off-label for weight loss at a healthcare provider's discretion. A healthcare provider may prescribe a compounded drug if he/she determines that it is medically appropriate and necessary. GLP-1 results are contingent upon a reduced calorie meal plan and increased physical activity. Cessation of GLP-1 has been found to result in weight gain.

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