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Ozempic and semaglutide have soared in popularity but how do they actually work and how safe are they?
It seems as though Ozempic and other weight-loss jabs are everywhere – and the appetite for them shows no signs of slowing down – with the industry accelerating so fast it’s projected to be worth $100 billion within the next decade.
Scientists are finding that semaglutide, the injectable drug within Ozempic pens, can not only help fight fat but reduce the risk of various forms of cardiovascular disease. Yet at the same time, given semaglutide’s side-effects, is Ozempic all it’s cracked up to be?
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Ozempic is a formulation of the drug semaglutide, which is used to treat Type 2 diabetes but which is prescribed off label for weight loss. In the UK, semaglutide is licensed for weight management and treating obesity under the brand name Wegovy.
Semaglutide is a synthetic drug that mimics the effects of a naturally occurring intestinal hormone called GLP-1, which is released after a meal. Developed by Danish pharmaceutical company Novo Nordisk, it targets multiple parts of the brain’s appetite control system, reducing hunger and cravings for food.
Dr Martin Whyte, associate professor of metabolic medicine at the University of Surrey, explains that semaglutide is one of several so-called GLP-1 drugs, which attempt to replicate the activity of the GLP-1 hormone.
“GLP-1 drugs lead to weight loss by creating a sense of satiety, meaning that people feel full up after eating less than they otherwise would have done,” says Dr Whyte. “This is achieved by the drug acting on the part of the brain called the hypothalamus, which tells us to feel hungry. I think these drugs have a huge role to play, although they are not a magic bullet for all the issues relating to obesity.”
As well as weight loss, studies have found that these drugs could have protective benefits for the heart. In August 2023, the results of a five-year study known as the Select trial were reported by Novo Nordisk, the manufacturer of Ozempic and Wegovy. The company revealed that a weekly 2.4mg dose of semaglutide could reduce the risk of heart attack or stroke in obese or overweight individuals with cardiovascular disease by a fifth.
The potential of semaglutide for treating weight loss first started to become known in 2021, after the results of a clinical trial were published in the prestigious New England Journal of Medicine.
Over 15 months, trial participants taking a weekly 2.4mg dose experienced an average of 15-17 per cent weight loss, with many shedding as much as 20 per cent of their starting weight. At the same time, they saw improvements in blood pressure and the levels of lipids or fats in their blood, both known risk factors for cardiovascular disease.
“This amount of weight loss is a lot more than you’d get from a diet,” says Prof John Wilding, a cardiovascular and metabolic medicine expert at the University of Liverpool, who ran the trial.
Prof Wilding explains that losing around 15 per cent of your body weight is associated with many health benefits for people who are overweight or obese. “If you’ve got diabetes, it’ll help with that,” he says. “If you’ve got pre-diabetes, there’s a good chance you’ll go back to having normal glucose regulation, and people’s ability to move is improved, which helps things like joint problems.”
Both Ozempic and Wegovy are injectable medicines that are self-administered on a weekly basis.
“It’s a once-weekly subcutaneous injection, via a pre-filled pen, into the fat under the skin of the belly, just in the same way that insulin is given,” says Dr Whyte.
It is not recommended to begin with the highest dose of either Wegovy or Ozempic. Instead, guidelines for Wegovy suggest starting with 0.25mg of semaglutide per week and then slowly going up to 2.4mg over the course of five months. This is to help mitigate against any side effects experienced.
The dose of semaglutide in Wegovy is slightly higher than in Ozempic. A maximum-strength Wegovy pen contains 2.4mg of semaglutide, compared to 2mg in a maximum-strength Ozempic pen.
“Most people will lose more weight with Wegovy as it has a higher maximum dose,” says Richard Holt, a professor of diabetes and endocrinology at the University of Southampton. “However, some people will achieve the weight loss they desire with lower doses.”
For diabetes patients using Ozempic, it is advised that they begin with 0.25mg for the first four weeks followed by 0.5mg for at least another four weeks. Patients are only suggested to step up to the 1mg or 2mg doses if they need additional blood sugar control.
As well as helping to regulate the appetite centre in the brain to create a sensation of early fullness, semaglutide also reduces hunger by slowing down the process by which food is emptied from the stomach and into the intestines.
“This process is called gastric emptying,” says Prof Holt. “By slowing the rate of food absorption from the gut, semaglutide also lowers blood sugar to a small extent.”
Research has suggested that there is a connection between fluctuating blood sugar levels and hunger. In 2021, a study in the journal Nature Metabolism found that so-called postprandial glucose dips, or the initial rise and subsequent crash in blood sugar levels two or three hours after a meal, are a good predictor of food cravings and subsequent food intake.
As well as slowing gastric emptying, it is thought that semaglutide stabilises blood sugar by increasing the amount of the hormone insulin produced by the pancreas in response to eating, while reducing the levels of another hormone called glucagon which acts against insulin to increase blood sugar. These mechanisms are why the drug is used to control diabetes.
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Experts emphasise that Wegovy and Ozempic cannot be solely relied upon as weight-loss solutions. “Semaglutide is a prescription-only medicine that should be used in conjunction with appropriate lifestyle and dietary changes to help control blood sugars,” says Dr Unnati Desai, a national GP lead at Nuffield Health. “The trials showed that for weight loss to be really effective, semaglutide should be prescribed to people who also access intensive behavioural change therapy to support them adopting healthier lifestyles.”
Prof Holt explains that the medication is ultimately a stop-gap approach to help people lose weight in the short-term, rather than a permanent option. While Wegovy is freely available on the NHS for a limited number of patients, it is approved to be used for a maximum of two years.
“Exit strategies are important with use of the medication,” says Prof Holt. “If it is stopped most, but not necessarily all, weight is regained over the following six months or so. This is why diet and exercise are so important in addition to using the medication, so that a healthy lifestyle might be better maintained after stopping the drug.”
For the last 20 years, GLP-1 drugs have also been investigated as possible Alzheimer’s treatments. This is based on initial research in the early 2000s in rodents which suggested that these drugs might be able to help protect neurons and other cell types in the brain.
The mechanisms that contribute to the development of Alzheimer’s disease are complex and multifaceted. They range from chronic inflammation in the brain to damage in the brain’s finely tuned blood supply which prevents vital nutrients from getting through.
One of the reasons why semaglutide is thought to have potential benefits for Alzheimer’s patients is because it acts to reduce insulin resistance, a condition where the body’s cells no longer respond properly to insulin. Studies have linked insulin resistance with neuroinflammation, and even an increased accumulation of the toxic beta amyloid protein in the brain.
“Although the pathology of Alzheimer’s disease is very complex, we know that neuroinflammation is a feature that plays a key role,” says Dr Tomas Welsh, the medical director of the Research Institute for the Care of Older People (Rice). “Evidence suggests that over time, chronic inflammation in the brain could result in the inability of neurons to communicate so they eventually die.”
Multiple clinical trials are now attempting to assess whether semaglutide can benefit patients in the early stages of Alzheimer’s, including two studies known as Evoke and Evoke+, both collaborations between Rice and Novo Nordisk.
“It might stop or slow some of the deterioration in the nerve cells that occurs in Alzheimer’s disease,” says Dr Welsh. “So it’s really exciting because it’s a different angle to look at Alzheimer’s. It’s not targeting clearing amyloid from the brain, like a lot of other drugs, it’s targeting another part of the disease pathway.”
At the same time, researchers are keen to point out that the version of semaglutide being used in these trials is not Ozempic, but a different formulation of the drug. As such, they urge patients to wait for the results of these studies rather than looking to purchase the forms of semaglutide currently on the market.
“It would not be correct to describe this investigatory medicine as Ozempic because it is an unlicensed investigatory use of semaglutide, and Ozempic is the brand name for it in Type 2 diabetes,” says Prof Naji Tabet, the director of the Centre for Dementia Studies at Brighton and Sussex Medical School.
The new class of semaglutide medications could have “far-reaching benefits” beyond weight loss including putting back the biological clock. Scientists published 11 studies together that suggest millions of people, including those who are not overweight, could potentially benefit from the drugs to improve quality of life.
Prof Harlan M Krumholz, one of Yale University’s leading professors, said the “mind-blowing” results showed the drugs appeared to slow down standard markers for ageing, in a way no other medication had achieved.
The scientist and editor-in-chief of the Journal of the American College of Cardiology said the injections acted as a “multi-drug” and “health promoter” which could do far more than any supplement or pill to extend life.
He added: “We have really strong evidence that yes, we may be putting people in a position to live longer and better. There are measures of how fast we’re biologically ageing and it wouldn’t surprise me that improving people’s health this way actually slows down the ageing process.”
Scientists said the impact of the medications reducing inflammation in the body appeared to explain why they can protect against such a wide range of diseases.
The development of many common and deadly conditions, including diabetes, cancer, Alzheimer’s and Parkinson’s disease has been linked to inflammation of the immune system.
The studies showed semaglutide was able to achieve astonishing results for cardiac medicine and improved conditions including high blood pressure and heart and kidney disease.
It was able to cut deaths by up to one-third, control previously untreatable blood pressure, and reverse kidney disease.
John Deanfield, a professor of cardiology at University College London, said that by targeting inflammatory biology, medicine could “alter the evolution and the consequences of multiple diseases”.
One of the reasons that Wegovy has attracted so much attention is because it is markedly more effective than any previous weight-loss therapeutics to have reached the UK market, such as:
Dr Varadarajan Baskar, clinical lead at the Birmingham-based Weight Loss Clinic and an endocrinologist at the South Warwickshire NHS Foundation Trust, explains that before GLP-1 drugs emerged, the only weight-loss medication approved on the NHS was orlistat. During one clinical trial, published in 2011, participants lost an average of more than 5 per cent of their starting weight over the course of six months.
“Orlistat blocks the intestinal absorption of fat by a third,” says Baskar. “Alongside diet and exercise, over a year you would find that the average additional weight loss with orlistat was to the tune of 3-5 per cent of starting weight.”
Another GLP-1-based weight-loss drug. A clinical trial published in 2015 found that participants lost an average of 7.9 per cent of their starting weight in just over a year.
Baskar points out that semaglutide not only yields greater reductions in weight, but is also more convenient for patients as it only requires weekly injections, compared to Saxenda which has to be injected on a daily basis.
“On average, weight loss achieved by patients on semaglutide is around twice that of Saxenda and three times that of orlistat,” says Baskar.
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Ozempic is currently only available on the NHS for the treatment of Type 2 diabetes. In September 2023, the NHS began prescribing Wegovy alongside a reduced-calorie diet and exercise, but only to individuals who had been referred to specialist weight-management services and had a body mass index (BMI) of 35 or greater and at least one weight-related health problem.
Both Wegovy and Ozempic can be obtained via a private prescription at select high-street chemists. However, Dr Desai cautions that not everyone can just buy the medication from their community pharmacy. It still requires assessment, prescription and ongoing support.
“Semaglutide is a prescription-only medicine,” she says. “The licenced use of Wegovy is in the management of clinically overweight patients with at least one weight-related comorbidity such as hypertension, hypercholesterolaemia, diabetes, cardiac disease, osteoarthritis or obstructive sleep apnoea. It is not recommended for those who have a normal or otherwise healthy weight.”
Baskar says that from his experience, the major side effects associated with Wegovy and Ozempic include:
“Early in the treatment course, these side effects are quite common,” he says. “Up to two thirds of patients may encounter some side effects. But studies have suggested that less than 7 per cent of people discontinue treatment altogether because they can’t tolerate them.”
According to Prof Holt, there are various proven strategies that people can adopt to ease any discomfort they might be experiencing. “Starting on a low dose and gradually increasing is one approach,” he says. “Or reducing the dose if necessary and eating smaller meals with less fat. With this, most people can continue treatment.”
Some rare but more serious side effects include:
Yes, especially if people are self-administering the drug. Taking too much can induce severe dehydration, fainting, headaches or migraine. One of the biggest risks of taking too much Ozempic is that it can cause severe hypoglycemia (low blood sugar). Symptoms can begin with increased heart rate, sweating and dizziness. More serious cases can cause confusion, delirium and coma.Other complications include severe gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain, constipation and pancreatitis (inflammation of the pancreas).
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While Dr Whyte says that long-term data on semaglutide is still being collected, the safety profile so far looks promising.
“To date, trials have gone up to two years,” he says. “It is noteworthy that GLP-1 drugs for diabetes became available in 2007 and long-term records of these drugs haven’t shown any increased signs of adversity, apart from nausea and constipation or diarrhoea in about 5 to 10 per cent of people and an increased risk of gallstones.”
Some of the more serious concerns around semaglutide are linked to pancreatitis, acute kidney injury and anxiety. In addition, studies in lab animals pointed towards a heightened risk of a rare type of thyroid cancer, but this occurred under much higher doses and no signs of this have been observed in humans.
Dr Desai says that because of the potential contra-indications to the medication, it is crucial that semaglutide treatment is only commenced after a full medical evaluation, including a blood test to ensure there are no underlying medical concerns. “Side effects that can occur, requiring the medication to be stopped immediately, include inflammation of the pancreas, gallstones, kidney disease, severe depression, allergic reaction or palpitations,” she says. “This medication cannot be prescribed in someone who has had or has a family history of thyroid or other endocrine cancers.”
According to Prof Wilding, while gallstones are a known hazard of weight loss that can occur with bariatric surgery or dieting, the risk of other severe side effects is small.
“Most of the other side effects that are talked about with these drugs are either very rare or may not be genuine issues, but they still have to be looked at, reported and considered,” he says. “But from what we’ve seen from the big trials [of semaglutide] in diabetes, these usually turn out to be non-issues.”
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