Ozempic, Wegoby, and GLP-1 have all become internet buzzwords. A miracle weight loss drug that makes you feel full and has minimal side effects? But there’s more to it than that. Numerous studies and clinical trials are underway to see if Ozempic and related drugs can treat a variety of heart, kidney, and liver diseases, as well as provide neuroprotection in neurodegenerative diseases and suppress compulsive behavior. It seems like a panacea, but is it really?
What are GLP-1 drugs?
Glucagon-like peptide-1 (GLP-1) is naturally secreted by the body after a meal to stimulate insulin production and control blood sugar levels, and its effect on insulin was first discovered in the late 19th century. 1980sIt would seem like a promising new treatment for diabetes, if only it weren’t for the problem that it is rapidly broken down in the blood.
That’s where the Gila monster comes in: a memorable name for a slow-moving, venomous lizard with a foul breath. One compound in its saliva is about 50% similar to GLP-1, enough to bind to the GLP-1 receptor, but… Long half-life This allowed it to be effective for a longer period of time. It was synthesized under the name exenatide and became the first GLP-1 receptor agonist (GLP-1RA) approved for the treatment of type 2 diabetes.
What are GLP-1RAs good for?
GLP-1RAs don’t just stimulate insulin secretion. They slow the emptying of the stomach into the intestine after a meal, which is one way of making you feel full. These are pathways that lead to blood sugar control, as well as weight loss, the main side effect of these drugs. After 68 weeks of treatment, people who were overweight or obese lost an average of 12 percent of body weight According to a 2021 study, this is solely due to the effects of the medication. These effects were seen with semaglutide, a next-generation GLP-1RA, best known by the names Ozempic, Wegovy and Ryversus.
It was at this time that GLP-1RAs really started to take off. After helping obese people lose weight, they were touted as helping anyone lose weight and sold like hotcakes.
Ozempic has become increasingly popular since it was approved in the United States in 2017 and in the EU, Canada and Japan in 2018. In recent years, it has become ubiquitous. Growing interest online Ozempic and Vigovi (FDA approved in 2021) are scheduled to be released at the end of 2022. Elon Musk claimed to be using the latter.It is not currently known whether non-obese or overweight people are taking GLP-1RAs, but the manufacturer of Ozempic reports that an increasing number of people are taking GLP-1RAs. High demand.
Now it seems like everything works. MultipurposeGabapentin was originally prescribed to treat epilepsy but is also commonly used as a painkiller, while sildenafil was developed to lower blood pressure and is best known for treating erectile dysfunction.
As Daniel Drucker, PhD, a clinical scientist and diabetes treatment expert at the Lunenfeld-Tanenbaum Institute, reports in a new Perspective, clinical trials are currently underway to test the effectiveness of GLP-1RAs as treatments for peripheral arterial disease; for preventing major cardiovascular events, stroke, kidney disease, and heart attacks; and for treating metabolic liver disease and Parkinson’s disease. Early studies are testing their potential as treatments for addiction-related behaviors.
If this seems like an overwhelming list of unrelated illnesses… it certainly is.
What do we know about how it works?
How can one drug, or one group of drugs, achieve all of this? The receptors to which these drugs bind, GLP-1R, are found in many different tissues and organs. Their expression in the pancreas is how they mediate their natural target effect on insulin secretion. They are also expressed in many different neuronal groups, for example in peripheral neurons that control gastric emptying and in central nervous system neurons that control food intake. Scientists have proposed the following pathways for these pathways: Mechanism of action Of these drugs.
GLP-1R is also expressed in the heart, liver and kidneys, but its mechanism of action in these tissues is unclear, and scientists have been unable to correlate GLP-1RA administration with disease outcomes. Understanding the mechanism.
One reason for the focus on the role of GLP-1RAs is that several theories about their magical mechanism of action have emerged. inflammationTaking GLP-1RAs appears to reduce inflammation throughout the body, from the gut to the brain, even in tissues that do not express the receptor, and reduced neuroinflammation is thought to underlie their therapeutic effects in neurodegenerative diseases.
Type 2 diabetes and obesity are associated with low-grade inflammation, but is the anti-inflammatory action of GLP-1RA necessary to achieve beneficial effects? It should be noted that some of these studies reporting therapeutic effects on the heart, liver, and kidney were performed only in patients with type 2 diabetes and/or obesity. Reducing inflammation in these tissues may reduce the risk of complications in these patients.
OK?
Are GLP-1RAs being overused and their potential drawbacks not being fully considered? Despite the large number of tissues and organs they target, they seem to have surprisingly few side effects, at least in the short term. Patients often Gastrointestinal discomfortOther symptoms include nausea, vomiting, diarrhea, abdominal pain and constipation. These are unpleasant conditions, but they can be treated.
Of greater concern is the loss of muscle mass. Although GLP-1RAs have powerful effects, they are not magic pills. Their use must be accompanied by lifestyle changes, particularly diet and exercise. GLP-1RAs reduce weight by suppressing appetite, so unless combined with exercise, they can actually Significant loss of muscle mass. people report Taking these medications can make it easier to stick to your diet and exercise routine.
Rare but more serious Side effects These include pancreatitis, retinopathy, gallstones, and malnutrition. It also appears to be associated with cancer risk, although the results on this are still unclear.
But in the long term, we don’t know. We are living through the “Great Ozempic Experiment.” The New York Times In other words, the challenge with these drugs is that once you start taking them, you’re on them for the rest of your life. If you stop taking them, the effects weaken. We have no idea what will happen if you take them for 10, 20, or 50 years, or what will happen if you stop taking them after a long period of time.
In addition to this, there is a growing problem of counterfeit GLP-1RAs circulating on the black market, with potentially even more dangerous side effects, which prompted the World Health Organization to issue a warning in June 2024.
GLP-1RAs have been used to treat type 2 diabetes for 20 years and are therefore suggested to be safe. They were approved for the treatment of obesity only 10 years ago and other potential uses are still being investigated. Risk-benefit analyses also need to be expanded to identify which patients will respond best to these treatments.
This outlook is Science.
