-small-thumbnail.jpg?v=1758880627)
GLP-1 agonists, such as Wegovy and Ozempic, are medications developed to help people with type 2 diabetes control their blood sugar. These medications became popular because they encourage weight loss, but new research suggests they could help with a wide variety of other illnesses.
- GLP-1 agonists are used to treat type 2 diabetes and to promote weight loss by improving insulin sensitivity and reducing appetite.
- GLP-1 is a hormone made in the gut, and it has wide-ranging effects on the body, including in the brain, bones, liver, and heart. This suggests that GLP-1 agonists may be able to treat other medical conditions.
- Research is producing promising results, but they are currently only FDA-approved for the treatment of type 2 diabetes, sleep apnea, obesity, and obesity-related cardiovascular disease. [1][2]
What are the main uses of GLP-1 agonists?
GLP-1 agonists are primarily used for treating diabetes and promoting weight loss. They re-create the actions of hormones known as incretins (specifically glucagon-like peptide-1), which stimulate insulin production and improve insulin sensitivity. [3] Insulin’s main function is to control blood glucose levels.
Diabetes can be treated by administering insulin directly, but this can create a difficult balance between having too much and too little insulin, potentially leading to dangerously high or low blood sugar. For people who need to avoid hypoglycemia (low blood sugar), a GLP-1 agonist may be beneficial, as it doesn’t require manually calculating the right insulin dose.
Although they are expensive, evidence indicates that GLP-1 agonists can be cost-effective due to the reduction in diabetes-related complications, which would otherwise require treatment. [35]
How do they work?
GLP-1 agonists are medications designed to mimic the GLP-1 hormone. They have the same effect as naturally-produced GLP-1, increasing the release of insulin from the pancreas, slowing gastric emptying (making you feel fuller for longer), and reducing glucagon production (reducing the conversion of intracellular sugars into blood glucose).[4]
Additional benefits of GLP-1 agonists
While GLP-1 agonists were developed to help with type 2 diabetes, researchers are seeing promising evidence that they could help patients with many other medical conditions.
Nonalcoholic fatty liver disease
Non-alcoholic fatty liver disease represents the build-up of fat in the liver, commonly associated with obesity. Early stages of the disease do not cause symptoms, but later stages can cause severe liver damage. [5] One key cause of non-alcoholic fatty liver disease is insulin resistance. [6]
The first-line treatment for non-alcoholic fatty liver disease involves lifestyle changes and weight loss. GLP-1 agonists accelerate weight loss, leading to improvements in fatty liver disease. By increasing insulin production, they counteract some of the insulin resistance. They also reduce liver fat and enzymes, further reducing non-alcoholic fatty liver disease. [7]
Alzheimer's disease
Alzheimer’s disease is a neurodegenerative dementia that appears to be caused by accumulations of beta amyloid plaques, as well as changes in how the brain metabolizes glucose.[8][9] Current treatments for Alzheimer’s disease reduce symptoms, but they can’t prevent or reverse the disease.[10]
Insulin can temporarily improve cognitive functioning in Alzheimer’s patients, but this is not an effective treatment outside of research studies. [11] More generally, improving glucose metabolism has been shown to slow, or even partially reverse, the cognitive decline associated with aging and dementia. [9][12] GLP-1 agonists reduce beta amyloid proteins, stimulate insulin production, and help to control glucose metabolism, allowing them to target multiple causes of Alzheimer's disease. [13] Further research is needed to investigate whether they offer an effective treatment.
Parkinson's disease
Parkinson’s disease is a neurodegenerative disease primarily caused by the selective loss of cells within a brain region called the substantia nigra. These cells normally produce dopamine, and the reduced dopamine levels in Parkinson’s disease lead to problems with movement and motor control, as well as other symptoms, including depression and dementia. [14]
It is unknown why dopamine-producing cells are lost in Parkinson’s disease, but one factor may be reduced sensitivity to insulin signalling in the brain. [15] GLP-1 agonists may compensate for reduced insulin sensitivity and possibly re-sensitize the brain to insulin. [16]
Small-scale human studies have been carried out with promising results. Larger studies are needed to see whether GLP-1 receptor agonists can prevent, stop, or reverse Parkinson’s disease. [17]
Osteoarthritis
Osteoarthritis is a common illness in later life, affecting around 10% of the population. [18] Reducing inflammation relieves pain and allows patients to continue to move their joints. Traditional anti-inflammatory pain medications (known as NSAIDs) do not address the cause of the disease, and they can cause problems in the cardiovascular, gastrointestinal, and renal systems. [19]
GLP-1 also has an anti-inflammatory effect. GLP-1 agonists may be more effective at reducing inflammation than endogenous (naturally produced) GLP-1 because these medications last significantly longer in the bloodstream. [20] GLP-1 agonists not only reduce pain in patients with osteoarthritis, but they may also address the cause.
Animal experiments suggest that osteoarthritis reduces the number of GLP-1 receptors in affected joints. [21] That same study found that using a GLP-1 agonist increased the number of these receptors, possibly reversing some of the effects of osteoarthritis. Other studies demonstrated that GLP-1 agonists can protect cartilage and reduce loss of bone density. [20] Given that GLP-1 agonists target many of the causes of osteoarthritis, these medications may be able to prevent the disease or stop it from progressing, but this still needs to be tested in humans.
Substance use disorder
GLP-1 agonists are postulated as potential treatments for substance use disorders. Their medication effects circulate throughout the body, meaning that they work wherever there are the correct receptors. GLP-1 receptors are not only found in areas of the brain associated with appetite, but they are also in areas responsible for processing reward, such as the ventral tegmental area (VTA) and nucleus accumbens. [22]
Studies have shown that GLP-1 agonists reduce alcohol consumption and alcohol-seeking behavior in rats. [23] This led researchers to wonder whether these medications could help treat substance use disorders in humans. Further studies in rats found that GLP-1 agonists reduced the amount of dopamine released following alcohol consumption and relapse-type behaviors. Similar effects have been found with cocaine, nicotine, and amphetamine use, as well as a reduction in preference for high-sugar diets. [3] It’s important to remember that animal studies are considered less reliable than human studies, as the results are not always reproducible.
Polycystic ovary syndrome (PCOS)
PCOS affects the fertility of up to 15-20% of women and is often associated with insulin resistance. [24] A combination of weight loss and restoring balance in the insulin system helps to restore fertility. [25] GLP-1 agonists may be able to treat PCOS, reducing the risk of adverse outcomes and improving fertility. [26]
Depression
Type 2 diabetes mellitus is associated with higher rates of depression. Studies found that patients taking GLP-1 agonists experienced less depression than those taking a placebo. [27] Researchers are exploring whether this effect also occurs for patients without diabetes.
Early in the use of GLP-1 agonists, concerns were raised about whether they increased suicidal thoughts in patients. Based on the evidence, the FDA has concluded that this is not the case, reducing the risks of taking GLP-1 receptor agonists for people with preexisting depression. [28]
Cardiovascular disease
Cardiovascular disease is the leading cause of death in people with diabetes, and some medications to control blood sugar can actually increase this risk. As a result, new medications for diabetes, such as GLP-1 agonists, are tested for their effects on cardiovascular disease. GLP-1 agonists have been shown to reduce the risks of cardiovascular disease for patients, whether or not they had diabetes.[29][30] This appears to be independent of their weight-loss effects.[ 31]
Current and future research
Research is ongoing to establish whether GLP-1 agonists can effectively treat all of these conditions. Of these, beyond type 2 diabetes, obesity, and sleep apnea, cardiovascular disease is the only illness for which there is enough evidence to receive FDA approval. Research on the use of GLP-1 agonists to treat some disorders, such as Alzheimer’s disease and substance use disorders, has mostly used animal models so far. Other uses, such as PCOS, have been tested on humans but still require larger-scale studies.
Another study looked at over 200,000 people who had taken GLP-1 agonists and compared the rates of different diseases with those of controls. This allowed researchers to spot diseases where GLP-1 agonists may be protecting patients, and future research could include psychosis, seizures, and coagulation disorders. [32]
-guide-detail.jpg?v=1722501965)
-guide-detail.jpg?v=1741692490)
