GLP-1 Peptide for Weight Loss

Exploring how the GLP-1 function may provide benefits beyond weight loss and diabetes

Obesity is one of the most significant public health challenges that we’re facing today. According to the World Health Organization, in 2022, 16% of the global population (around 890 million people) were living with obesity, with 160 million being children or adolescents. These rates have contributed to an increase in type II diabetes, estimated to affect over 6% of the world’s population, causing nearly 1 million deaths per year.

Pharmaceutical breakthroughs in GLP-1 and GIP receptor agonists are now changing the narrative around obesity and type II diabetes. Various GLP-1 and GIP receptor agonist-based weight loss drugs such as Ozempic, Wegovy, Mounjaro, and Victoza are the latest blockbuster treatments for obesity and, because they lower blood glucose, type II diabetes as well.

Researchers are finding that these drugs may also be applicable to other diseases. By examining the CAS Content Collection TM, the largest human-curated repository of scientific information, we can identify not only the growth in overall research and patents related to GLP-1 and GIP receptor agonists, but also the co-occurrences of these drugs with conditions beyond type II diabetes and obesity. The results are promising, but many hurdles to clinical usage remain.

What is the GIP and GLP 1 mechanism?

Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are incretin hormones secreted by the intestines that stimulate insulin production after ingesting food. Agonist medications mimic the GLP-1 hormone by binding to cell receptors and causing the same action as the natural hormones, namely, insulin secretion for regulating blood glucose levels.

These agonists have multiple effects, such as lowering blood glucose by triggering insulin release and blood glucagon release. They also delay gastric emptying and promote a longer feeling of satiety (see Figure 1).

Figure 1: Illustration demonstrating the secretion and effects of GLP-1 and GIP peptides on various organs (Individual icons for building illustration sourced from www.biorender.com)

What other conditions can GLP-1 and GIP receptor agonists treat?

The use of GLP-1 and GIP agonists has increased steadily in the last two decades, with most growth understandably relating to obesity and type II diabetes. However, our analysis of the CAS Content Collection revealed many other important co-occurrences of these agonists with various conditions in existing literature (see Figure 2). In fact, there are currently more than 200 clinical trials underway for GLP-1 and GIP receptor agonists, suggesting growing interest in their ability to treat other diseases:

• Cardiovascular conditions: GLP-1 and GIP receptor agonists have shown cardioprotective benefits and reductions in major cardiovascular events such as stroke. Studies have noted that GLP-1 receptor is expressed at low levels in the heart and vascular system, which raises the possibility that the GLP-1 function may directly and indirectly affect the cardiovascular system. It’s possible that GLP-1 receptor activation could reduce cardiovascular morbidity by reducing glycaemia, blood pressure, inflammation, and body weight.
• Neurodegenerative diseases: Conditions such as Parkinson’s and Alzheimer’s involve protein misfolding and chronic inflammation, among other pathologies. Studies have found that GLP-1 mimetics can cross the blood-brain barrier and have neuroprotective effects, including reducing oxidative stress and chronic inflammatory responses in the brain. Certain mimetics have even reduced beta-amyloid plaques in animal models.
• Liver disease: Non-alcoholic fatty liver disease affects up to 30% of adults in the Western hemisphere, and GLP-1 receptor agonists have shown promising results in increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism.
• Cancer: As seen in Figure 2, co-occurrences of GLP-1 and GIP receptor agonists and cancer have increased in recent years, particularly in 2023. This is due to studies investigating the potential effects of these drugs on thyroid- and pancreatic-related cancers. At this point, researchers have found neither firm evidence for a connection between these drugs and cancer nor have they definitively ruled out increased risks. It is likely we’ll continue to see the co-occurrences in literature as more studies continue on these potential effects.

Figure 2: The co-occurrence of GLP-1 and GIP receptor agonists with various health conditions. Numbers are based on data mined using the CAS Content Collection (2003-2023) where terms were searched using keywords (including synonyms) and were searched in title, abstract, and CAS-indexed terms.

Which GLP-1 and GIP receptor agonists are commercially available?

While journal publications still outnumber patent publications relating to GLP-1 and GIP receptor agonists, we’ve seen significant growth in patent documents in recent years (see Figure 3). The patent-to-journal has steadily increased, which indicates the growing commercialization of these drugs owing to the potency of the GLP-1 function.

Figure 3: Number of journal and patent publications published per year relating to GLP-1 and GIP receptor agonists over the last two decades (2003-2023) from the CAS Content Collection. The minor dip in data for 2023 could be due to the ongoing curation efforts of publication-related data for 2023.

Numerous drugs have been approved and are now available on the market, including:

• Exenatide (Bydureon, Byetta): Exenatide is a synthetic version of a hormone, exendin-4, which mimics GLP-1 action, thereby stimulating insulin production. It is used for the treatment of type II diabetes.
• Lixisenatide (Lyxumia [EU], Adlyxin [US]): These agonists were developed for treating type II diabetes and have been shown to have neuroprotective effects and reduce inflammation.
• Liraglutide (Victoza, Saxenda): These drugs have the highest number of associated documents in our analysis of the CAS Content Collection (see Figure 4A). Liraglutide is a GLP-1 receptor agonist and apart from weight and blood sugar management, it has also shown benefits for patients with cardiovascular diseases and stroke.
• Dulaglutide (Trulicity): This is a GLP-1 receptor agonist that stimulates insulin secretion and inhibits glucagon secretion, thereby promoting satiety and slowing gastric emptying.
• Semaglutide (Ozempic, Wegovy, Rybelsus): These medications have been in high demand since their FDA approval for weight loss, and Wegovy was recently approved for preventing serious cardiovascular conditions such as heart attack and stroke.
• Tirzepatide (Mounjaro, Zepbound): These medications target both GLP-1 and GIP receptors. By mimicking GLP-1, tirzepatide increases insulin secretion, reduces glucagon release, and slows gastric emptying. As a GIP mimic, this medication further enhances the body’s ability to use insulin and promotes satiety. In Figure 4B, we see the precipitous growth of this agonist in recent years.

In Figure 4, we can see the co-occurrences of these drugs with various conditions. As expected, the maximum co-occurrences are with diabetes, weight loss, and obesity. We also find co-occurrences with cardiovascular and neurological disorders, which reinforce how these agonists show potential in treating these conditions. Their correlation with cancer in this analysis is likely because of studies into potential links between agonists and various cancers, but as noted, more research is needed to understand the increased risks.

Figure 4: (A) Distribution of various GLP-1 and GIP receptor agonists (B) Yearly growth of various GLP-1 and GIP receptor agonists in the last decade (2011-2023) (C) Sankey chart showing the co-occurrence of various kinds of GLP1 and GIP receptor agonists with different health conditions. The numbers are based on data mined using the CAS Content Collection (2003-2023) where terms were searched using keywords (including synonyms) and were searched in title, abstract, and CAS-indexed terms.

What is the future of GLP-1 and GIP receptor agonists?

GLP-1 and GIP receptor agonists have given hope to millions of people struggling with obesity and type II diabetes. They are breakthrough treatments for weight management and managing blood glucose levels and may confer additional benefits in treating neurodegenerative diseases, liver disease, and more.

The recency of their widespread clinical usage, however, means we don’t fully understand all of their potential side effects. The benefits of these drugs must outweigh the risks, and researchers still have much to learn about the long-term effects of these drugs.