GLP-1s: Your No-Nonsense Guide To The Latest Science Behind The “Skinny Jabs”

Everybody’s talking about GLP-1s. These drugs, first used in patients with type 2 diabetes and more recently as apparently “miraculous” weight loss aids, have become inescapable in online discourse over the last couple of years. Ozempic, Wegovy, and Mounjaro are almost as recognizable as Tylenol and Tums. But what does science actually know about these drugs?

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Glucagon-like peptide-1 receptor agonists, shortened to GLP-1RAs or often simply GLP-1s, were born out of an unlikely discovery involving Gila monsters, the largest and only venomous lizards in the US. Scientists found that a compound in these lizards’ saliva could bind to naturally occurring GLP-1 receptors in the human body, promoting the production of insulin and improving blood glucose control.

The first drug synthesized from lizard saliva was called exenatide and was licensed for use in type 2 diabetes. A few years down the line, the next generation – semaglutide – arrived. 

It was semaglutide, an active ingredient in both Ozempic and Wegovy, that really kickstarted broader awareness of these drugs, helped along no doubt by some frustratingly catchy ad campaigns. There’s also tirzepatide, marketed as Mounjaro or Zepbound, and liraglutide. 

They’re still used for blood sugar management in people with type 2 diabetes, to great effect – a recent survey reported that 25 percent of US adults with a diabetes diagnosis were using a GLP-1RA in 2024, often in combination with insulin or other treatments. But the real buzz around these drugs grew as it became clear they could also be used as weight loss medications. 

GLP-1RAs as weight loss drugs

There’s no doubt that GLP-1RAs can be effective for weight loss. Just how effective is trickier to pin down. Obesity is highly complex, despite what snappy TikTok soundbites might want you to believe. There are many factors that contribute to someone’s weight and body composition, and it really can’t all be narrowed down to simply what people are eating. 

But it’s also true that diet has a role to play. People who have lost weight with the help of a GLP-1RA often talk about how the drugs silence “food noise”, allowing them to focus less on food and consequently eat less. That’s because these drugs literally decrease your appetite, sometimes significantly, and slow down the emptying of the stomach. 

The lack of appetite can also be compounded by side effects like nausea and diarrhea. The frequency of these side effects, as well as the high cost of the medications, have been identified as factors that can discourage people from continuing to take the drugs, which may then result in weight regain. 

Access to these drugs also varies considerably. For example, in the UK, prescribing guidelines at time of writing state that the drugs should only be offered to people with clinically defined obesity or diabetes, “and not if you want to lose weight for aesthetic or cosmetic purposes.” Mounjaro and Wegovy can be offered to people for weight management in combination with exercise and diet plans, whereas Ozempic is currently only available to those with diagnosed type 2 diabetes.

Restrictions on prescribing haven’t stopped a thriving black market for GLP-1RAs and products touted as alternatives. The World Health Organization is one among many authorities to warn of the dangers of counterfeit semaglutide, which can contain incorrect or undisclosed ingredients and come with considerable health risks. 

So, it’s not just about whether a GLP-1RA would work for an individual on a pharmacological level – it’s whether they can access it, can afford to continue taking it long-term, and can withstand any side effects. 

We hear a lot about these acute side effects, like gastrointestinal distress. Some people won’t get these at all; some will get them only mildly or temporarily; some will find them unbearable. But there’s another aspect to consider, one science is really only starting to learn about: what are the long-term effects of GLP-1RAs?

What we know – and what we don't

Some people are concerned that the rapid and significant weight loss that can come with taking a GLP-1RA can have the knock-on effect of decreasing lean muscle mass, and that the loss of appetite could cause nutritional deficiencies. One study found that 20 percent of adults taking a GLP-1RA had a nutrient deficiency within the first year, and the authors suggested that patients be offered support from professionals like dieticians as part of their care. 

As for muscle loss, this is a particular issue as people age because it puts them at greater risk of falls and physical disability. A recent study found lots of conflicting data in the literature about just how significant this issue could be – some research suggested that up to 60 percent of total weight loss could be from lean muscle mass, while others found it was more like 15 percent. More research will be needed to fully unpack the scale of this problem and how best to tackle it. 

Off-target effects

GLP-1 receptors don’t only exist in the digestive system – they’re found in cells throughout the body, so it stands to reason that taking a GLP-1RA can have what scientists call “off-target effects”. This just means that a drug does something else beyond what it was designed and approved to do, and it’s not always a negative thing. Just look at Viagra. 

A large study published in January this year attempted to assess the scope of off-target effects of GLP-1RAs by looking at 175 different health outcomes. Unsurprisingly, given how common gastrointestinal side effects are, the study confirmed that there’s a risk of more serious issues, including gastroparesis (paralysis of the stomach) and inflammation of the colon, as well as pancreatitis. Other potential negative effects included sleep issues and an increased risk of kidney stones.

The authors of the January study stressed that it was observational, so it’s impossible to tell from the data if any of the effects are a direct result of taking a GLP-1RA. For example, an increased risk of kidney stones could come from dehydration caused by lack of appetite, rather than an effect of the drug itself. 

And the picture painted by the study was not all negative – far from it, actually. These drugs also appear to be associated with a range of health benefits, some of them surprising. 

Dementia

It’s possible that these drugs could decrease the risk of Alzheimer’s disease-related dementia, something that’s since been corroborated by other researchers. A recent study suggested that in dementias involving the pathological protein tau, such as Alzheimer’s, faulty processing of glycogen (stored glucose) could be at fault, which might explain why GLP-1RAs look like a promising avenue. 

Cancer

One concern that’s been raised repeatedly is whether taking a GLP-1RA can increase the risk of cancer, particularly pancreatic cancer. However, a range of recent studies have found the opposite – that these drugs may actually protect against certain forms of cancer. 

On the pancreatic cancer question specifically, a study of over 540,000 adults found “no support for an increased pancreatic cancer incidence over 7 years following start of GLP-1RA treatment.” The authors note that longer follow up is still needed, however, and it’s important to consider how the use of these drugs has skyrocketed recently. 

One paper in March this year concluded that there was “significant heterogeneity in the effects of GLP-1RAs across different cancer types.” There’s some evidence they might protect against colorectal, prostate, and liver cancer, but may increase the risk of thyroid cancer. 

Bringing things right up to date, a paper published just last week also added to the evidence that GLP-1RAs can protect against certain cancer types in patients with obesity. This was especially clear for endometrial and ovarian cancers, and meningiomas. However, the study did find a non-significant increased risk of kidney cancer that would merit further investigation. 

Commenting on the study for Science Media Centre, Professor of Cancer Epidemiology Paul Pharoah said, “While these results suggest that GLP1 receptor agonist have an effect on cancer risk the presence of an association does not mean that the association is a causal one.”

“An observational study, no matter how carefully conducted, cannot replicate a randomised controlled trial, which would be regarded as gold standard to evaluate the effects of a drug.”

Inflammation

We said some of the documented effects of GLP-1RAs were surprising, and that pretty much all bodily systems could be fair game. A recent study that illustrates this well discussed the potential of these drugs as treatments for chronic inflammatory skin disease hidradenitis suppurativa (HS). The condition causes excruciatingly painful lesions associated with apocrine sweat glands, which are found in certain regions of the body – the underarms, groins, and genitals are often affected.

The small study followed patients for six months and found that 54 percent experienced a reduction in their symptoms after taking a GLP-1RA. Most of the patients had type 2 diabetes and the median BMI of the cohort was 39.4, which is classified as within the obese range.

Higher body weight is considered to be among the risk factors for developing HS, though the causes are not fully understood, so it’s possible that in these patients the weight reduction was what alleviated their symptoms; but it's possible these drugs have an anti-inflammatory effect, so the authors suggested that further randomized clinical trials could be warranted.

The bottom line

A new survey from RAND found that almost 12 percent of American adults surveyed had taken a GLP-1RA, and 14 percent said they were interested in doing so. Of course, that leaves almost three-quarters who said they had no interest in taking them, but even at these percentages, we’re talking about quite a lot of people.

The most notable usage was in women aged 50-64, among whom 20 percent reported having used a GLP-1RA at least once.

GLP-1RAs are still comparatively new, and they have not previously been in use on this scale. There are a lot of open questions that scientists are actively researching, and we’re going to learn more and more about their potential applications and side effects in years to come.

For now, the decision to start taking a GLP-1RA, as with any prescription medication, is one that should be taken under careful consideration of the known benefits and harms, and in collaboration with medical professionals.

The content of this article is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of qualified health providers with questions you may have regarding medical conditions.