Hello friends,
It’s been a while since I’ve written on my blog, for all the reasons you might imagine: work, child, studying…a whole list of excuses. But today, spurred by a provocative media program, I decided to sit down and write a few lines about the modern medicinal solution in the battle against excess weight—what are commonly referred to as “GLP-1s” or more widely known by the name of one of the drugs: “Ozempic.”
Obesity is a growing global problem, which not only worsens the quality of life but also increases the risk of numerous health complications, including type 2 diabetes, cardiovascular diseases, and some types of cancer.
What are GLP-1 receptor agonist drugs, and what is their history?
GLP-1 is a hormone (incretin) secreted by enteroendocrine cells in the intestines after a meal. It plays an important role in regulating glucose by increasing insulin secretion and inhibiting glucagon secretion.
The history of GLP-1 receptor agonists begins with discoveries in the fields of endocrinology and metabolism, which helped understand the role of glucagon-like peptide-1 (GLP-1) in regulating blood sugar and appetite. In the 1990s, research showed that GLP-1 could lower blood glucose levels, leading to increased interest in its clinical application, especially in patients with type 2 diabetes. Synthetic analogs of these molecules began to be developed to overcome the issue of their short half-life (due to rapid degradation by enzymes in the gastrointestinal tract).
In 2005, the first GLP-1 agonist drugs were approved:
- Liraglutide (Victoza, Saxenda): Approved for the treatment of type 2 diabetes.
- Exenatide (Byetta, Bydureon): The first GLP-1 agonist approved for clinical use.
In the following years, new GLP-1 agonists were developed and approved, such as:
- Dulaglutide (Trulicity): Approved in 2014, with a dose administered once a week.
- Semaglutide (Ozempic, Wegovy, Rybelsus): Approved in 2017, also with a weekly dose. Wegovy received approval for obesity management in 2021.
- Tirzepatide (Mounjaro, Zepbound): In 2022, the new combined drug Mounjaro, which also acts as a GIP agonist, was approved, showing even greater effectiveness in clinical trials for weight and glucose control.
How do GLP-1 receptor agonists work?
GLP-1 receptor agonists, like liraglutide, dulaglutide, semaglutide, and tirzepatide, have a well-established role in the treatment of obesity and type 2 diabetes. They work through various mechanisms, some of which are still being studied. Here are some of the mechanisms by which these drugs work:
- Stimulation of insulin secretion: They help boost insulin production in response to rising glucose levels.
- Slowing gastric emptying: This allows for a quicker and longer-lasting feeling of fullness.
- Reducing appetite: These medications make patients feel less hungry by acting on brain centers that regulate hunger and satiety.
- Changes in eating habits: Incretins can influence preferences for certain foods, reducing cravings for calorie-dense and fatty foods.
- Leptin-ghrelin balance: They can increase the body’s sensitivity to leptin (a hormone that signals fullness) and reduce ghrelin (the “hunger hormone”).
- Increase in thermogenesis: Some research suggests that incretins may increase energy expenditure through heat production.
- Improvement in physical activity: Patients taking GLP-1 agonists may report more energy, improving fitness levels and helping maintain weight.
- Anti-inflammatory effects: Incretins can also have anti-inflammatory properties, improving metabolism by reducing inflammation in the body.
The benefits of this class of medications are numerous, and it’s no surprise that, although created to manage endocrine-metabolic diseases, they have also gained interest in cardiology circles. Many studies on GLP-1 receptor agonists and the combination drug tirzepatide have shown significant improvements in the three major adverse cardiovascular events often evaluated in clinical trials: myocardial infarction, ischemic stroke, and cardiovascular death. Reducing the risk of cardiovascular events provides additional support for the use of these medications, especially in patients with existing cardiovascular diseases or increased risk of such events.
As a longevity medicine student in Geneva, I must share the definitive role of this class of drugs in longevity medicine. We already know they play an important role not only in managing type 2 diabetes and obesity but also in therapeutic strategies for longevity interventions, improving quality of life in older age. Incretins improve cognitive function and may have neuroprotective properties, reducing the risk of age-related neurodegenerative diseases like Alzheimer’s through their anti-inflammatory and antioxidant effects.
We can see for ourselves that this relatively new class of drugs has many health benefits across different areas, and new applications continue to emerge (for conditions like fatty liver disease, sleep apnea, addictions, etc.). However, it is important not to assume they can be prescribed indiscriminately. The improper use of GLP-1 receptor agonists, including new combined medications like Mounjaro, is a growing concern in medical circles. The focus is on the misuse of these drugs by individuals who do not meet established treatment criteria.
Here are some key aspects related to improper use:
- Prescription criteria: GLP-1 receptor agonists and Mounjaro are typically approved for:
- Type 2 diabetes.
- Obesity in patients with a body mass index (BMI) over 30 kg/m² or a BMI over 27 kg/m² with associated metabolic complications.
Improper use includes prescribing or purchasing them for people who do not meet these criteria, such as those wanting to lose weight without medical justification. Misuse can lead to side effects such as nausea, vomiting, constipation, diarrhea, reflux, headache, and in rare cases, pancreatitis.
Patients who do not consult with a medical professional may ignore the risks and contraindications of these medications, which can pose a serious health risk. Education and awareness of the proper use of these drugs are key to preventing unwanted consequences and promoting a healthy lifestyle and sustainable weight management. Doctors play a vital role in providing proper guidance and monitoring patients for safe and effective treatment results.
On the horizon, we also see new peptide molecules from the incretin group (like retatrutide, cagrilinide, and others), which show even more promise regarding weight and overall health. However, their safety has not yet been fully studied or approved by regulatory agencies like the FDA or EMA. Despite this, some “garage” manufacturers of peptides are offering them online, supposedly for experimental purposes, and some colleagues, even without recognized specialties in endocrinology or metabolism, are offering them to their patients.