Ozempic and Wegovy are being heralded as ‘revolutionary’ weight-loss drugs disrupting the entire weight loss industry, but is there a trade-off? We delve into the science behind semaglutide drugs.
Semaglutide, an injection medication initially used for regulating blood sugar levels in Type 2 diabetes patients, is being hailed around the world as a weight loss “wonder drug” – just ask Elon Musk, who credits the blockbuster drug for his recent weight loss.
Known under the brand names Ozempic, Wegovy and Mounjaro, semaglutide has generated excitement in the pharmaceutical and medical industries, all but promising a new frontier in tackling obesity. Astonishingly, US health care providers wrote more than 9 million prescriptions for Ozempic and similar drugs in the final three months of 2022.
Its rising popularity began after the FDA approved Wegovy, a higher-dose version of Ozempic, as a treatment for chronic obesity in June 2021. Since then, whispers are rife on the red carpets that a growing number of celebrities and influencers are taking the drug off-label for rapid weight loss.
Despite semaglutide’s optimistic headlines around the globe, rumoured (and confirmed) uptake in Hollywood and impressive clinical trial results (more on that later), the drug is not without its controversies. Many remain cautious about side effects and the implications of its widespread off-label use – including accessibility to those medically in need and a possible link to cancer, as well as its potential impact on societal beauty standards and perpetuation of unattainable ideals.
What is semaglutide?
Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue, which is approved for treating type 2 diabetes in adults and mitigating cardiovascular risks in individuals with both type 2 diabetes and heart disease. It is delivered through subcutaneous (under the skin) injections at doses up to 1mg once a week.
This medication imitates the natural hormone GLP-1, which slows down stomach activity and helps individuals feel full for a more extended period. Additionally, it seems to impact the way the brain regulates appetite.
In an earlier study to observe the ‘effects of GLP-1 on appetite and weight’, US scientists at the Mayo Clinic explained that GLP-1 originates from the pre-proglucagon gene expressed in various parts of the body, such as the pancreas, intestines, and specific neurons in the brain.
They described how GLP-1 ‘is of relevance to appetite and weight maintenance because it has actions on the gastrointestinal tract as well as the direct regulation of appetite. It delays gastric emptying and gut motility in humans. In addition, interventricular injections of GLP-1 inhibit food intake, independent of the presence of food in the stomach or gastric emptying.’
The Mayo Clinic researchers also highlighted that GLP-1, when administered peripherally, impacts central feeding regulation. Thus, the combined actions of GLP-1 in the gut and brain, interacting with central and peripheral receptors, seem to be responsible for the hormone’s effect on satiety.
Shedding 16% body weight
In a major US clinical trial conducted at the University of Pennsylvania, researchers examined 611 participants to explore the effects of semaglutide drug, Wegovy. The research focused on adults who were overweight or dealing with obesity but had no diabetes.
In the study, the overweight or obese volunteers without diabetes were injected once-weekly with either 2.4mg of subcutaneous semaglutide (407 volunteers) or a placebo (204 volunteers) for 68 weeks to determine the effect on body weight when added to intensive behavioural therapy with an initial low-calorie diet.
Alongside these injections, all participants followed an intensive behavioral therapy program which included an initial 8-week very low- calorie diet that transitioned to a low- calorie diet, weekly exercise routines scaling from 100 to 200 minutes, and 30 visits from a dietitian.
The results, published in the renowned Journal of the American Medical Association (JAMA), revealed a remarkable difference in weight loss between the two groups. Those receiving semaglutide injections experienced a 16.0% decrease in body weight, averaging a loss of 16.8kg, whereas the placebo group only saw a 5.7% reduction. This notable difference was determined to be statistically significant. The study authors highlighted the importance of semaglutide as a supplementary treatment alongside an intensive therapy program and an initial low-calorie diet. This combined approach led to significantly increased weight loss among overweight and obese adults.
Additionally, they emphasised the benefits of weight loss in terms of improving cardio-metabolic risk factors: ‘Weight loss improves cardio-metabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective non-invasive weight loss approaches.’
A new frontier in weight management
Commenting on the University of Pennsylvania study of semaglutide, The Sydney Morning Herald declared: ‘The emergence of the new drug, marketed locally as Wegovy, promises to revolutionise weight-loss treatments.’
Professor Brian Oldfield, a leading obesity researcher at Monash University, told SMH: ‘As these drugs become more effective and available, it will be harder for people to ignore them.’
Although governments worldwide have invested significantly in public health campaigns to promote healthy eating and exercise, these efforts have not caused significant weight loss.
‘While healthy eating and physical activity are vital for good health, decades of evidence suggest they simply do not lead to large amounts of weight loss,’ said Prof Oldfield. ‘They are not enough by themselves. They typically give a 3-5% reduction in body weight.’
As such, introducing a new drug like Wegovy could make a significant difference in the fight against obesity.
Tiffany Petre, director of the Obesity Collective, shared a similar sentiment, expressing her hope that semaglutide drugs like Wegovy will change conversations about obesity in society. ‘People with obesity haven’t been able to get appropriate healthcare. Now
there is something on the market,’ she said.
Risks and Controversies
Ozempic and Wegovy’s rise in popularity have also been accompanied by various claims and controversies surrounding its usage and side effects.
Commonly reported side effects include reflux, nausea, vomiting, constipation, diarrhoea and abdominal pain. In some instances, more serious side effects can occur, such as severe allergic reactions, kidney problems, pancreatitis and diabetic retinopathy.
Ozempic has also been linked to an increased risk of developing thyroid cancer in animal studies. Although there is currently no definitive evidence that the medication poses a similar risk in humans, it has resulted in a warning on the drug label.
There is also the question of what happens to your body after stopping Ozempic or Wegovy. Like many medications, semaglutide only works for as long it’s used. As soon as you stop taking it, any weight loss is likely to come back. More worryingly, if you abruptly stop using it, the amount of glucose in your body can spike due to sudden shifts in blood sugar levels and may cause serious medical complications.
Concerns have also been raised about the massive uptake in individuals who do not have diabetes or obesity and are using the drug for “quick fix” weight loss. This hyper-demand for off-label weight loss – seemingly reserved for the wealthy elite who can afford paying prices of up to US$1,300 a month – has led to a shortage of semaglutide medications for people who medically need them.
‘We’ve had instances where patients have not been able to get some of their current medications for their diabetes, because there is a shortage of those due to the uptick of patients using this off label for weight loss,’ says Dr Andrew Straw, associate professor of pharmacy practice at Cedarville University in the US.
Dr Steven Heymsfield, a professor of metabolism and body composition at Louisiana State University in the US, agrees that unintended use, as opposed to prioritising semaglutide for treating chronic obesity, is worrying.
‘I’m very concerned about this rage for these GLP-1 agonists,’ he told Verywellhealth.com. ‘These drugs should be used for people who really need them and have health risks from obesity who’ve tried many times to lose weight, and not by Hollywood actors and actresses who are trying to lose 10 pounds.’
Further, Dr Paul Jarrod Frank, a dermatologic surgeon in New York, warns that off-label use of semaglutide may come with more than just weight loss. ‘Using this drug to maintain a body weight that is low for one’s frame is not the intended purpose and is most likely a dangerous and unsustainable use of the medication,’ he told Allure.com.
Malnutrition & ‘Ozempic Face’
Another risk of Ozempic use is malnutrition. Dr Andrew Wong, an internal medicine specialist in the US, told healthnews.com: ‘Some patients who have been taking Ozempic for a while have reported symptoms of eating disorders, such as abnormal eating patterns, meal skipping and late-night munching. Others lost the elasticity and the collagen in the muscles in the face, which may be a symptom of malnourishment.’
US plastic surgeons have reported an increase in patients seeking treatment for ‘Ozempic face’ and ‘Ozempic body’ – the loose, sagging skin caused by rapidly losing weight after taking Ozempic and Wegovy.
Semaglutide drugs themselves do not cause loose skin, but it can cause patients to lose weight faster than other forms of weight-loss methods, including bariatric surgery. Dr Paul Jarrod Frank first coined the term ‘Ozempic face’ after many of his middle-aged patients would come in with gaunt faces after losing a lot of body weight in a short period of time while on the weight- loss drug.
Dr Dhaval Bhanusali, a NY dermatologist, told The New York Times that he’s seen an increase in patients on semaglutide medications who are concerned about facial ageing and sagging. ‘We are seeing more and more patients on the medications coming in,’ he said. ‘Generally, it’s people in their 40s and 50s who are losing significant amounts of weight and are concerned about facial ageing and sagging that occurs as a result.’
New York plastic surgeon Dr Ryan Neinstein, who regularly treats patients seeking treatment for loose skin after bariatric surgery, told insider.com that he’s increasingly seeing people with the same issue, or ‘even stretchier, looser skin than bariatric patients’, after taking Ozempic – due to ‘muscle mass and fat decreasing so quickly’.
Dr Neinstein noted loose skin after weight loss can be temporary, and most people see skin return to normal 6-18 months following bariatric surgery; hence, his first approach in helping Ozempic patients is the same as with bariatric surgery: encouraging patience and plenty of exercise.
Exposing cracks in the body positivity movement
Many social commentators believe the run on Ozempic and the attention- grabbing headlines it’s garnering is reinforcing and perpetuating unattainable beauty. They argue the Ozempic craze has revealed some major cracks in the self-love movement and is undoing much of the body positivity progress we as a society have fought so hard to achieve.
A recent article in Time.com says, ‘the popularity of this new drug [Ozempic] is increasing the weight of the pressure to pursue thinness’ and that ‘it’s clear that the unlearning and undoing of a century’s worth of harm by the rise of the “body positivity movement” is regarded as just another trend.
‘The Ozempic craze is a swift wind that has revealed that we’ve spent the past decade building a house of cards.’
Risk & Reward
It’s important to remember Ozempic and Wegovy are not magic solutions and carry risks and side effects. Like all prescription medication, they should only be prescribed when medically necessary. They should also be accompanied with lifestyle changes including a nutritious diet and regular exercise.
Nevertheless, many experts agree this new set of weight-loss drugs signal significant progress. The pursuit of an efficient, reliable method for weight control to address the long-standing public health issue of obesity has been challenging. This new class of drugs, repurposed from diabetes treatments, represents an entirely new therapeutic area and suggests a promising novel approach to obesity treatment.
As Tim Spector, a professor of genetic epidemiology at King’s College in London, told NYPost.com, ‘The field has been waiting for a blockbuster drug in this area for decades and this group of drugs looks like it fits the bill.’ CBM
