Why is Everyone Jumping on the Ozempic Bandwagon? Understanding the History and Considerations Before Using GLP Agonists

The Evolution of GLP-1 and GLP-4 Agonists

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-4 (GLP-4) agonists have revolutionized the treatment of diabetes and metabolic disorders. These medications have a fascinating history, from their initial discovery to their current status as essential tools in managing chronic conditions. In this blog, we'll explore the origins, development, and impact of GLP-1 and GLP-4 agonists.

The Discovery of GLP-1

The story of GLP-1 begins in the 1960s and 70s when scientists were investigating glucagon, a hormone produced by the pancreas that raises blood sugar levels. During this research, they discovered proglucagon, a precursor molecule that could yield multiple peptides. In the early 1980s, researchers successfully mapped the amino acid sequence and gene responsible for proglucagon, leading to the identification of GLP-11.

In 1986, a pivotal study led by Mojsov et al. identified GLP-1 (7-37) within the intestines. This discovery marked a turning point, revealing GLP-1 as an active hormone with distinct biological functions. The following year, scientists discovered GLP-1's powerful ability to stimulate insulin release, offering a safer alternative to earlier diabetes treatments by reducing the risk of hypoglycemia1.

The Development of GLP-1 Agonists

The therapeutic potential of GLP-1 was quickly recognized, leading to the development of GLP-1 receptor agonists. These medications mimic the action of the GLP-1 hormone, helping regulate blood sugar levels by stimulating insulin secretion and inhibiting glucagon release. GLP-1 agonists were initially developed for type 2 diabetes but have since been approved for treating obesity and other metabolic disorders2.

One of the most significant breakthroughs in GLP-1 research came from an unexpected source: the Gila monster lizard. Researchers discovered that the saliva of the Gila monster contained a compound (exendin-4) similar to GLP-1. This finding led to the development of exenatide, the first GLP-1 receptor agonist approved for clinical use.

The Impact of GLP-1 Agonists

GLP-1 agonists have had a profound impact on diabetes and metabolic health care. They have been shown to lower blood sugar levels, promote weight loss, and reduce the risk of cardiovascular events. Additionally, GLP-1 agonists have been found to have neuroprotective effects, sparking interest in their potential for treating neurodegenerative conditions like Alzheimer's disease.

The Discovery and Development of GLP-4 Agonists

While GLP-4 is less well-known than GLP-1, it has also played a role in advancing metabolic health care. GLP-4 agonists work by activating the GLP-4 receptor, which helps regulate glucose metabolism and insulin sensitivity. The development of GLP-4 agonists has followed a similar trajectory to that of GLP-1 agonists, with researchers exploring their potential for treating diabetes and other metabolic disorders.

Modern-Day Use of GLP-1 Agonists

Glucagon-like peptide-1 (GLP-1) receptor agonists have become a cornerstone in the treatment of type 2 diabetes and obesity. These medications mimic the action of the GLP-1 hormone, which helps regulate blood sugar levels and appetite.

Here's a summary of their modern-day use:

Diabetes Management

GLP-1 receptor agonists, such as exenatide, liraglutide, semaglutide, and dulaglutide, are widely used to manage type 2 diabetes. They work by:

Stimulating insulin release from the pancreas.
Suppressing glucagon secretion, which helps lower blood sugar levels.
Slowing gastric emptying, which reduces post-meal blood sugar spikes.
Reducing appetite, leading to weight loss.

These combined effects make GLP-1 receptor agonists effective in improving glycemic control and reducing the risk of cardiovascular events.

Obesity Treatment

GLP-1 receptor agonists have also been approved for the treatment of obesity. Medications like liraglutide (Saxenda) and semaglutide (Wegovy) have shown significant weight loss benefits. Clinical trials have demonstrated that these medications can lead to substantial weight loss, which is sustained over time with continued use.

Cardiovascular Benefits

In addition to their effects on blood sugar and weight, GLP-1 receptor agonists have been shown to reduce the risk of major cardiovascular events, such as heart attack and stroke. This makes them a valuable option for patients with type 2 diabetes who are at high risk for cardiovascular disease.

Emerging Uses

Research is ongoing to explore the potential of GLP-1 receptor agonists in treating other conditions, including:

Type 1 Diabetes: While primarily used for type 2 diabetes, GLP-1 receptor agonists are being investigated for their potential benefits in type 1 diabetes, particularly for patients with insulin resistance.
Neurodegenerative Disorders: There is interest in the neuroprotective effects of GLP-1 receptor agonists, with studies exploring their potential in treating conditions like Alzheimer's disease.
Metabolic Liver Disease: GLP-1 receptor agonists are being studied for their potential to improve liver health in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

Addiction Medicine

Semaglutide, a GLP-1 receptor agonist, is not considered addictive in the traditional sense. However, it does interact with the brain's reward pathways, which has led to some interesting observations. Some patients have reported a reduction in cravings for substances like alcohol and nicotine while taking semaglutide. This suggests that semaglutide may have a modulating effect on certain addictive behaviors, but it is not classified as an addictive substance itself.

Modern GLP-1 Ozempic and Thyroid Cancer

Ozempic, a brand name for semaglutide, is a medication commonly used to manage type 2 diabetes and aid in weight loss. While it has proven to be effective in these areas, there have been concerns about its potential link to thyroid cancer. In this blog, we'll explore the relationship between Ozempic and thyroid cancer, examining the research, risks, and what you should consider before using this medication.

Understanding Ozempic

Ozempic belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists. These drugs work by mimicking the action of the GLP-1 hormone, which helps regulate blood sugar levels by stimulating insulin secretion and inhibiting glucagon release. Ozempic has been shown to be effective in lowering blood sugar levels and promoting weight loss, making it a popular choice for individuals with type 2 diabetes.

The Link Between Ozempic and Thyroid Cancer

Concerns about the potential link between GLP-1 receptor agonists like Ozempic and thyroid cancer stem from preclinical studies conducted on rodents. These studies suggested that long-term exposure to GLP-1 receptor agonists could increase the risk of thyroid tumors, particularly medullary thyroid cancer (MTC), a rare form of thyroid cancer.

However, it's important to note that these findings have not been consistently replicated in human studies. Research involving humans has not shown a definitive link between Ozempic and an increased risk of thyroid cancer. The European Medicines Agency (EMA) and other regulatory bodies have reviewed the available evidence and concluded that there is no clear association between GLP-1 receptor agonists and thyroid cancer in humans.

Overdiagnosis Concerns

Recent studies have raised concerns about the overdiagnosis of thyroid cancer in individuals using weight loss medications like Ozempic. The increased screening and medical imaging associated with these medications may lead to the detection of harmless thyroid nodules, resulting in unnecessary cancer diagnoses. This phenomenon highlights the importance of careful evaluation and consideration before attributing thyroid cancer cases to the use of Ozempic.

Who Should Avoid Ozempic?

While the overall risk of thyroid cancer associated with Ozempic appears to be low, certain individuals should exercise caution. People with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN 2) are advised to avoid using Ozempic and other GLP-1 receptor agonists. It's essential to discuss your medical history and any potential risks with your healthcare provider before starting this medication.

Are there alternatives to GLP agonists? Making the case for Metformin

Both semaglutide and metformin are medications used to manage type 2 diabetes, but they have different mechanisms of action, administration methods, and benefits.

Mechanism of Action

Semaglutide: Semaglutide is a GLP-1 receptor agonist. It mimics the action of the GLP-1 hormone, which stimulates insulin secretion, inhibits glucagon release, and slows gastric emptying. This helps lower blood sugar levels and promotes weight loss.
Metformin: Metformin belongs to the biguanides class. It works by improving the body's sensitivity to insulin, reducing glucose production in the liver, and increasing glucose uptake by muscles. This helps lower blood sugar levels.

Both semaglutide and metformin are effective in managing type 2 diabetes, but they have different mechanisms of action, administration methods, and benefits. Metformin is often used as a first-line treatment due to its long history of use, effectiveness, and low cost. Semaglutide, on the other hand, offers additional benefits such as significant weight loss and cardiovascular protection, making it a valuable option for certain patients.

Conclusion

The history of GLP-1 and GLP-4 agonists is a testament to the power of scientific discovery and innovation. From their initial identification to their current status as essential tools in managing chronic conditions, these medications have transformed the landscape of diabetes and metabolic health care.

GLP-1 receptor agonists have transformed the landscape of diabetes and obesity treatment, offering significant benefits in glycemic control, weight loss, and cardiovascular health. As research continues, their potential applications may expand even further, providing new hope for patients with a variety of metabolic and neurodegenerative disorders.

Ozempic has proven to be an effective medication for managing type 2 diabetes and promoting weight loss. While concerns about its potential link to thyroid cancer have been raised, current research does not support a definitive association between Ozempic and an increased risk of thyroid cancer in humans. However, individuals with a history of thyroid cancer or related conditions should consult their healthcare

As research continues, we can expect even more breakthroughs and advancements in the treatment of these conditions.

Personal reflection

As more and more patients are running towards the use of GLP-1 for both weight management and the treatment of metabolic disorders, many are forgetting the value of keeping active and adopting good eating habits. At the end of the day creating and maintaining lean muscle mass and staying physically active promote better health. More and more studies have shown the incidence of muscle loss while on GLP agonists. Those who decide to add GLP agonists to their medication arsenal should keep in mind of the importance and value of adding and or increasing resistance training and ensure adequate protein intake. These strategies can help preserve muscle mass and maintain overall physical function

Disclaimer: Always consult your healthcare professional before starting any new treatment, exercise program, or dietary plan. This information is provided for educational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Individual results may vary.