by Paul Joyce,The Conversation

Credit: Unsplash/CC0 Public Domain

You've probably heard of Ozempic or Wegovy. These are the injectable drugs that have become household names for weight loss and diabetes.

Now, researchers are investigating whether these medications known as GLP-1 agonists or GLP-1 drugs could treat everything from cancer and brain disease to depression, addiction and endometriosis.

Some findings are genuinely exciting. Others are being oversold. Here's what the science actually says.

First, how do these drugs work?

GLP-1 (glucagon-like peptide-1) is a hormone your gut naturally releases after eating. It tells your pancreas to produce insulin and signals to your brain that you're full. These drugs mimic that hormone.

But GLP-1 receptors aren't just in the gut. They're found in the heart, kidneys, liver and brain. That's what makes scientists think these drugs might do far more than manage weight.

Where the evidence is already solid

Beyond diabetes and obesity, GLP-1 drugs have now earned regulatory approval in several new areas.

Atrial of more than 17,000 peoplefoundsemaglutide(the active drug in Ozempic/Wegovy) cut the risk of serious heart attacks and strokes by 20%, even in people without diabetes.

In atrial of almost 1,200 patients, semaglutide outperformed a placebo in treating a type of advanced liver disease.

Tirzepatide (Mounjaro) has also been shown to significantlyreduce the severity of sleep apnea, mostly because weight loss puts less pressure on the airways.

GLP-1s and cancer: Promising but no clinical trial evidence

Obesity is a risk factor for at least13 cancers, so reducing weight using GLP-1 drugs can also be expected to limit cancer risk. This was shown in astudyof 86,000 adults with obesity. It foundGLP-1 usershad a 17% lower cancer risk.

New datasuggests GLP-1 users were also less likely to see cancer spread to other organs, but this work is yet to be verified by other researchers. The anti-inflammatory effects of these drugs, which appear to work independently of weight loss, may be playing a role.

However, there have not yet been any well-controlled clinical trials that establish the link between GLP-1 drugs and preventing cancer.

Endometriosis: Early but promising signs

Endometriosis affects roughly1 in 10 womenof reproductive age. This is where tissue similar to the womb lining grows outside the uterus.

BecauseGLP-1 receptorsare also present in reproductive tissue, these medications have shown promise in improving symptoms, with asurvey of 161 womensupporting this.

But, similar to cancer, there are no randomized human trials.

Addiction and smoking

GLP-1 receptors are concentrated in the brain's reward pathways. These same circuits drive cravings for alcohol, nicotine and drugs.

An analysis ofmore than 1.3 million peoplefound GLP-1 users had significantly lower rates of opioid overdose and alcohol intoxication.

A randomized trialfound semaglutide reduced drinking in people with alcohol use disorder.

Earlyquit-smoking trialsare encouraging, too.

The brain: The least clear picture for GLP-1 therapy

This is where the story gets genuinely complicated.

There are real biological reasons GLP-1 drugs could help with neurodegeneration and mental ill-health. They reduce brain inflammation, interact with dopamine (the brain's motivation chemical) and support the gut-brain axis (the communication network that carries signals to and from the gut and brain).

However, current clinical evidence is conflicting.

For Alzheimer's disease,researchers gave 204 participantswith mild to moderate disease liraglutide (a GLP-1 that pre-dated Ozempic) and measured how much brain volume they lost. Those taking the drug showed significantly lessshrinkagein key brain regions, including their temporal lobe and overall gray matter.

However, alarge phase 3 trialof oral semaglutide found it wasn't effective at slowing clinical disease progression.

Similarly, exenatide (another earlier GLP-1) showed no evidence for disease modification in aphase 3 Parkinson's disease trial.

For mental health, current evidence is also mixed.Meta-analysesandlarge cohort studiesshow significant reductions in depression and anxiety scores among GLP-1 users.

But a separateobservational studyfound people on these drugs had almost double the risk of major depression.

Anotherpaperfound that people with a genetic tendency toward low dopamine levels may face higher risk of depression and suicidal thoughts on these medications.

There are alsocase reportsof serious psychiatric episodes appearing within weeks of starting treatment.

We don't yet know who these drugs will help, and who they could seriously harm.

What we need to be cautious about

Crucially, most of the new uses for these medications haven't yet been tested in proper clinical trials. Large real-world studies are useful, but they can't rule out crucial confounding factors. This means the effects may be due to external influences.

For example, most major GLP-1 trials have enrolled people with obesity or diabetes. People with mental health conditions, neurodegenerative diseases, or addiction were largely excluded. Yet, these are the very populations now being considered for treatment.

Long-term effects are also unknown. Astudy of more than 200,000 patientsfound a 2–2.5 times higher risk ofdrug-induced pancreatitis(dangerous inflammation of the pancreas).

Rapid weight loss also strips lean muscle, not just fat, affecting strength and metabolism, especially in older adults.

Studies have also indicated these medications carry arisk for thyroid cancer, prompting a warning on drug labels, but evidence is highlyconflicting.

Time and further research will tell, but there are genuine safety concerns associated with the widespread use of these medications.

So, while the science here is genuinely exciting, we should continue to approach with informed caution.

This article is republished fromThe Conversationunder a Creative Commons license. Read theoriginal article.

Key medical concepts GLP-1 Receptor Agonist [EPC] Semaglutide Tirzepatide Alzheimer's Disease Endometriosis