Rates of overweight and obesity in Australians since the 1990s have skyrocketed – and men have been leading the charge.
Cathy O’Leary looks at how doctors are using a more nuanced approach with anti-obesity medications to help turn the tide.
Australians – young and old – have stacked on the weight in the past few decades and the reasons why are part of a complex web of evolutionary, physiological, environmental and societal changes.
According to the most recent data from the Australian Institute of Health and Welfare, two-thirds of adults – about 13 million people – were overweight or obese in 2022, a significant increase from 56% in 1995.
Men in particular have become a lot bigger – with a staggering 71% of them carrying too much weight in 2022 compared to 61% of women.
It comes at a hefty cost to individuals as well as public health. Overweight and obesity are red flags for a range of diseases and chronic conditions, including cancer, cardiovascular disease, type 2 diabetes and musculoskeletal disorders.
Men are more likely than women to die prematurely of heart disease and cancer, and weight is often a key factor.
At the pointy end of the weight crisis are the 32% of Australian adults who are obese and therefore potential targets for anti-obesity medications such as the semaglutides Ozempic and Wegovy and the newer kid on the block tirzepatide (Mounjaro).
A watershed moment
Many doctors believe healthcare has reached a watershed moment, where the undeniable results from these blockbuster drugs have changed forever the way obesity is viewed and managed – with it no longer seen and approached purely as a lifestyle choice.
But how best to use them, to get the biggest bang for their buck, is now attracting big interest from scientists, doctors and the government bean counters under pressure to fund the medicines on the Pharmaceutical Benefits Scheme (PBS).
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And there could be other benefits from anti-obesity medications beyond weight loss, with research presented at the European Congress on Obesity in Spain in May this year finding that first-generation weight-loss medications like liraglutide and exenatide appear to have anti-cancer benefits.
Ozempic (semaglutide) is probably the best-known name among the group of medicines known as glucagon-like peptide-1 receptor agonists (GLP-1RAs), which mimic the naturally occurring hormone GLP-1 to tell the brain that the stomach is full.
But like many of the new anti-obesity drugs, it is approved on the PBS only as a diabetes treatment, so patients using them only for weight loss have to pay hundreds of dollars for each private script.
It is a sore point with them and the GPs who are increasingly being asked to prescribe these popular medicines.
The RACGP recently called for effective obesity management medication to be subsidised on the PBS to address what it says are big health inequities – with the medicines currently only available to those who can afford them.
The change in the peak body for GPs’ position on medication for weight loss follows the RACGP’s release of a new position statement on obesity prevention and management in February this year.
The College said more government funding for longer GP consults was also essential in supporting people who were overweight or obese.
RACGP Specific Interest Obesity Management Chair Dr Terri-Lynne South said there was growing evidence that semaglutide medicines were an effective way for patients to reduce their risk of developing complex and chronic conditions that were linked to overweight and obesity.
She said manufacturers had drawn “exceptional profits” from these medications and they needed to invest in reducing costs for patients.
“If a medicine is effective and safe, and the cost of a condition to the health system outweighs the cost of treating it with a medicine, there’s also a strong case to subsidise that medicine,” she said.
“The evidence for semaglutide and similar GLP-1 receptor agonists as effective weight loss medicines is if not at, then approaching, that point.”
New kid on the block
While Ozempic captures most of the headlines, the newer drug tirzepatide is garnering growing interest. Since last year, Australian GPs have been able to prescribe it to patients for obesity.
It is available to adults with an initial body mass index of ≥30 kg/m2 or ≥27 kg/m2 in the presence of at least one weight-related comorbid condition such as hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, pre-diabetes or type 2 diabetes.
Tirzepatide has been likened to a master key that unlocks two important doors in the body’s weight control system, by mimicking the hormones GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), whereas semaglutide only acts on GLP-1.
Both drugs trick the brain into making people feel full, so they eat less and instead burn fat stored in the body.
Some research suggests tirzepatide (Mounjaro) may have the edge over Ozempic and Wegovy, affecting feelings of hunger and fullness, as well as changing how the body processes food.
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The first head-to-head trial of two blockbuster weight loss drugs – undertaken in the US recently – concluded that Mounjaro is more effective than rival Wegovy.
Both drugs led to sub
stantial weight loss, but Mounjaro’s 20% weight reduction after 72 weeks of treatment exceeded the 14% from Wegovy, according to the trial’s findings.
Researchers who led the trial at the Comprehensive Weight Control Center at Weill Cornell Medicine in New York said both drugs had a role, but Mounjaro might help those with the most weight to lose.
In the UK, private sales of tirzepatide are now reportedly well ahead of those of semaglutide, but the huge amount of global research into weight loss drugs means it is a dynamic field of medicine, and more pharmaceuticals are already in the pipeline.
Perth research deep dive
In Perth, UWA researchers are taking a strong interest in tirzepatide, but with an important add-on which they believe makes it a better and safer weight loss treatment.
Their current study is investigating how to maximise the benefits of the new blockbuster anti-obesity medication by combining it with a tailored exercise program to address a potential downside of significant weight loss – a decrease in muscle or lean mass.
They have recently been trying to recruit more men to sign up for the study, known as T-REX.
Led by Professors Bu Yeap and Daniel Green, the research examines whether combining tirzepatide with structured exercise gives better outcomes for cardiovascular health, compared to medication alone.
Already they are urging doctors who are prescribing anti-obesity medications to be aware of the need for resistance exercise to combat changes in body composition such as muscle loss.
Prof Green, from UWA’s School of Human Sciences, said all participants in the randomised study were receiving 40 weeks of free treatment with Mounjaro and half of them also had the chance of getting a free state-of-the-art exercise program supervised by a specialised exercise physiologist at the UWA gym.
“The medication being studied has shown remarkable effectiveness in clinical trials, exceeding that of Ozempic and produces weight reduction of 15-to-20% over a 40-week period,” he said.
“However, questions remain about how to optimise their health benefits beyond weight loss alone.”
The researchers had already recruited more than 100 women and men when Medical Forum spoke to them but still had openings for more male participants.
Prof Yeap said several of the men who had already completed the treatment course had described their experience as “life-changing”.
The study allowed men and women to receive a highly effective treatment in a carefully supervised environment. As part of the study researchers are testing heart and artery function, so they need people who are not on blood pressure or cholesterol-lowering medication and have not previously been on Ozempic or other weight loss drugs.
Prof Yeap, an endocrinologist with UWA’s Medical School, told Medical Forum that with both semaglutide and tirzemide people could get decent weight loss in the obesity setting.
“But what we also now realise is that you lose a bit of lean mass as well, and a big chunk of that is muscle, and that might not be so good in the longer term,” he said.
“If you lose muscle, you’re losing a site where a lot of glucose is consumed, and if you lose muscle then it may increase your risk of becoming frail and having sarcopenia (progressive muscle disorder) frailty, so what we want to do is look at that in more depth.
“We also want to know whether if you’re going to use tirzepatide or semaglutide, or any of the other ones that are going to be coming up soon, is the best way to do it with a resistant exercise program that will protect your muscle mass?
“And apart from protecting the muscle mass, you maybe even lose more fat.”
Prof Yeap said the exercise needed to be weight-bearing resistance types – with upper and lower body exercises – and in the study it was being done in the gym at UWA so it could be monitored.
“We’re also going to look at the cardiovascular side of things in a lot more detail, so we’ll be looking at vascular and cardio function using echocardiograms, looking at what happens when you lose a lot of weight with these anti-obesity medications, and how is that affected when you’re combining it right from the onset with a resistant exercise program.
“So we should be getting some really good data on vascular function and cardio function.”
The researchers believe the scale of lean mass loss associated with some incretin therapies for diabetes could be greater than that seen during 10 years of ageing, while preserving lean mass in obesity treatments could also prevent rebound fat gain when people stop their pharmacotherapy.
“We know these drugs work, they’re really effective, and losing a huge amount of fat is very beneficial, but what we’re trying to figure out is the best way to use them with a proper resistance exercise program, as opposed to simply telling people to maintain their protein intake and exercise,” Prof Yeap said.
“In terms of overweight and obesity, in the past 20 years the figures have got worse, so if we’re looking at the early 1990s to 2018 across the Australian population, the average BMI has really gone up.
“It’s a problem that’s been getting worse in the past couple of decades, and we now have the chance to treat it effectively medically, so it’s exciting times but what we want to know is whether you get the best effect by having an exercise program as well as medications.”
Prof Yeap said they had a strong hypothesis, after canvassing the use of incretin therapy for type 2 diabetes in a paper published in Diabetes Care last year.
“We think there is a very sound rationale behind this, but we have to prove it scientifically. We have to get high quality evidence and the only way to do it is through a randomised trial, so everyone in the study is getting background medications, and the randomisation is for the exercise intervention versus the usual.”
Advice to GPs
Although the study is yet to finish, there was already some advice to share with GPs and other health professionals.
“It’s probably not a bad idea to draw to everyone’s attention that this is a possible concern – losing lean muscle mass – and obviously we’re looking at it very carefully,” Prof Yeap said.
“But it wouldn’t hurt when doctors are talking to patients about to start this treatment for them to discuss things like protein intake and resistance exercise and encourage all of them to take it onboard.
“We really should be recommending everyone in the Australian population do resistant exercise, but probably more so in this scenario.”
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Meanwhile, Monash University researchers recently cautioned that while the new anti-obesity medications were seen as wonder drugs, the approach to managing patients needed to be nuanced.
Their review in the Medical Journal of Australia said key considerations included funding models, prescribing pathways, and guidelines for treatment duration, including prevention of rebound weight gain after patients stop using the drugs.
“Because of how these new medications work, they’re transforming the way we view obesity as a condition,” Associate Professor Suong Le, a gastroenterologist at Monash University’s School of Clinical Sciences wrote.
“It’s clear that obesity is not just a lifestyle choice but should be regarded as a chronic inflammatory disease with links to cancer, brain function and autoimmune conditions.
“In Australia, we need to focus on researching more niche, specific-use cases where these medications can make a meaningful difference in our clinical practice while also developing a greater understanding on how exactly they lead to improved cardiovascular health, kidney function and neuroprotection.
“This will help us develop a more nuanced and scientifically comprehensive understanding of obesity as a condition and a risk factor for other diseases.”
ED: For more details of UWA’s T-REX study email the research team at trexstudy-shs@uwa.edu.au
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