Obesity is a complicated public health issue that can be devastating on both the societal and the individual level. On one hand, it costs our economy millions and is a strain on our underresourced health system. On the other hand, it is a psychological and physical burden to those who are acutely affected – individuals who inevitably face stigma at every turn, with undeserved overlays of blame and shame.

The conventional approach, telling patients to diet and exercise, fails on its own. Some experts have even described it as “cruel”. New medicines that have been shown in clinical trials to be remarkably effective and relatively safe are priced so high that very few can afford them. Any intervention on its own will not solve the crisis, but will adding these drugs to the arsenal help turn the tide?

‘An uphill battle’

“I have been trying to lose weight, I’d say for at least 20 years,” says Claire (not her real name), a 43-year-old woman who lives in the south of Johannesburg.

“I’ve tried all the diets, cut sugar, cut carbs – I do end up losing a little if I follow them to the T, but the weight always comes back. I was on a diet last year that I followed religiously for four months and I only lost 4kg. All that effort and stress and at the end of it I thought, what’s the point?”

In February, Claire visited her GP because she was experiencing fatigue. She was diagnosed as pre-diabetic with elevated insulin levels. Her doctor offered her Ozempic, a drug registered to treat diabetes in South Africa that is being used off-label to treat overweight and obesity.

Just more than two months later, Claire has lost 17kg. The combination of the drug, a good diet and moderate activity levels has resulted in a massive drop in weight from 140kg to 123kg. It is the kind of success story that sounds almost too good to be true, but Claire’s story chimes with findings from several large clinical trials.

Mind-blowing. Breakthrough. Liberated. These are some of the words she uses to describe the impact the drug has made on her life and health in only a couple of months, on the back of more than two decades of trying and failing to lose weight the conventional way.

The reality is that almost every medical condition is associated with obesity and the cost to the country is enormous.

“It’s just been an uphill battle that I believed I was never going to win. The more I tried, the more depressed I got. For the first time in forever, I’m positive, motivated, hopeful. It’s not just the physical weight – but the weight that’s been lifted from me psychologically,” she says.

It hasn’t come cheap. At R2,500 a month, she has had to make sacrifices to be able to afford it.

“But it’s worth it. For the first time, I don’t have to constantly focus on how many breadcrumbs I’m eating. I can get on with life. I feel free,” she says.

The obesity epidemic

Excess weight is a public health problem of epidemic proportions across the globe, particularly in South Africa, where half of all adults are considered to be overweight (23%) or obese (27%).

Rates in children and teenagers are also extremely high. According to Unicef, almost one in every three girls between the ages of 15 and 19 is living with obesity or is overweight.

In South Africa, half of all adults are considered to be overweight (23%) or obese (27%). (Photo: MagnusD / Flickr)

The World Obesity Federation estimates that, by 2030, adult obesity rates in South Africa will increase to 37%.

According to the head of wellness at Discovery Vitality, Dr Mosima Mabunda, obesity is defined as a body mass index (BMI) over 30. BMI is calculated using a person’s total weight divided by their height squared. A BMI over 27 is considered overweight. She said BMI alone is insufficient to assess risk and waist circumference should also be taken into account.

The perception that excess weight is an aesthetic problem instead of a public health problem is still rife, according to Professor Julia Goedecke from the South African Medical Research Council (SAMRC). “But the reality is that almost every medical condition is associated with obesity and the cost to the country is enormous,” she says.

For example, women with a BMI over 30 have a 12 times higher risk of developing type 2 diabetes compared with those with a healthy BMI. People who are overweight have a 32% higher risk of developing coronary heart disease, while those with obesity have an 81% higher risk. There is also a fourfold increased risk of developing severe Covid-19 in people living with obesity.

These elevated risks extend to a host of other serious and even life-threatening conditions, from strokes, various cancers, lung disease, and musculoskeletal disorders to things like depression, gout, gallstones and chronic kidney disease.

There is a big focus on willpower when it comes to obesity, but it’s not down to willpower when the body is doing its damnedest to conserve calories.

In 2020, the total combined direct cost of overweight and obesity in South Africa was estimated to exceed R33-million, according to research conducted by the South African Medical Research Council and Wits Centre for Health Economics and Decision Science (Priceless SA). This figure equates to 15% of the total government health spend and represents 0.67% of the country’s GDP. The true economic toll is much higher, since these estimates don’t take into account all the indirect costs from lost productivity or obesity-related premature death.

“For me, these statistics are a wake-up call for us to make concerted efforts to slow down and reverse the trend,” says Mabunda.

The status quo

The World Health Organization classified obesity as a disease in 1948. Almost 80 years later, the stigma and debate about accepting obesity as a disease and independent health risk factor continue to stymie anti-obesity efforts.

The accepted medical advice, the standard “prescription” given to patients by healthcare workers – diet and exercise – “doesn’t work and often only makes it worse”. This is according to Professor Francois Venter, who heads up Ezintsha, a multidisciplinary research centre at the University of the Witwatersrand.

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“It has become quite clear that, for the majority of people who have excess weight gain, it is next to impossible to shift it over the medium to short term. Crash diets and exercising frantically do shift weight down but it almost always comes back and often even overshoots,” he says.

No one can deny the fact that lifestyle factors such as unhealthy eating habits and a lack of physical activity drive obesity rates and that a strong focus on these two interventions is important to prevent obesity as well as to prevent someone with obesity from gaining more weight. But for patients who already find themselves in the obese or overweight categories, he says, the lifestyle prescription alone is a completely inadequate treatment that fails much more often than it succeeds.

Venter points to the “body weight set point theory” or “thermostat theory” by way of explanation. The body’s weight regulation mechanism is continuously reset upwards as a person gains weight and is “triggered by the amount of adipose tissue in fat cells or the size of fat cells at that time”. At a certain point, the body recognises the higher level of fat as the norm and will work to maintain it, interpreting weight loss as a threat to the equilibrium.

Some experts say the accepted medical advice given to patients to diet and exercise falls short and more is needed. (Photo: Nenad Stojkovic / Flickr)

“For example, a person who weighs 90kg may lose 5kg. In response, the body will fight tooth and nail to get back to 90kg,” explains Venter.

The body does this by releasing hormones that promote hunger in an effort to gain calories that can be returned to fat cells where they will be stored.

“Hunger is such an unpleasant feeling and sensation, and it is very hard to fight. There is a big focus on willpower when it comes to obesity, but it’s not down to willpower when the body is doing its damnedest to conserve calories,” he says.

The bottom line is that this thermostat is much more easily reset up than down.

He says it is “cruel” to continue to only offer this advice to patients, knowing it won’t achieve positive results but only adds to their psychological burden.

Obesogenic food environment

“Problematising individuals and their lifestyle choices in isolation is short-sighted. The problem is actually a policy issue, a failure to regulate the food environment,” says the Healthy Living Alliance’s Lawrence Mbalati.

He says we are living in an “obesogenic” environment that encourages and promotes the consumption of high-calorie processed food with little nutritional value.

According to Mabunda: “It turns out that the environmental effect on behaviour is a lot stronger than most people expect.

“Excess consumption of sugar contributes to the rising obesity epidemic. Yet sugar remains widely available/accessible in the foods and beverages that many of us consume. Research tells us that sugar activates our brain’s pleasure centre, thus making it difficult for individuals to resist high-sugar foods and beverages.”

Mbalati says that compared with unhealthy options, healthy food is costly – a problem that can only be solved through regulation, for example, by subsidising healthy options and taxing products high in sugar, salt, and fat.

Other factors like regulating advertising, especially to children, and enforcing clear and easy-to-understand labelling on packaged food products are also important, he says.

Mabunda explains that the environment works in ways we can’t mediate through willpower alone. She said that, when we are tired or stressed or rushed, the rational part of the brain is compromised and automatic behaviour takes over.

“If you have a plate of cookies in front of you in a meeting or a workshop, at some point you will most likely fall into the temptation to grab a cookie. Motivation and willpower wane, which is why we need regulation and collaboration between public health bodies, food retailers, and manufacturers. [So] how do we design an environment where people are psychologically nudged to choose healthier food?”

After a lengthy process that was vehemently opposed by industry, a tax on sugary beverages, called the Health Promotion Levy, was introduced in South Africa in early 2018. It has resulted in relatively modest reductions in consumption of these drinks but notably resulted in positive actions by industry. For example, many products were reformulated to contain less sugar, and packaging sizes were made smaller.

While these bigger-picture issues are important, they will take a lot of time and political will to change. Passing legislation is a protracted and difficult process.

But public health experts argue that it is unethical to do nothing in the short term.

“We need a solution to offer patients right now,” says Venter.  

GLP-1 agonists

Enter Ozempic and its counterparts – the wave of anti-diabetic agents that have been found to be effective for weight loss.

The glucagon-like peptide-1 agonists (GLP-1) are a class of drugs initially developed for the treatment of type 2 diabetes, but more recently, they have been shown to be highly effective for the treatment of obesity and overweight.

“These drugs have essentially hacked the system,” says Venter. “They trick the brain into thinking the thermostat is lower than it is.”

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He says that the drugs allow patients to eat healthily, without needing to conform to a strict diet, without “the constant craving and background noise that makes you so tired all the time” and helps people “maintain a health plan with much less effort than before”.

How do they work?

“GLP-1 is actually a naturally occurring hormone found in the human body,” explains Johannesburg-based endocrinologist Dr Sundeep Ruder.

In response to food, cells in the intestine release GLP-1 as a normal part of the metabolic process. “The hormone travels to the brain and links to the appetite centre, reducing hunger and increasing satiety. Satiety is not just feeling full but feeling satisfied,” says Ruder.

Excess consumption of sugar contributes to the rising obesity epidemic. (Photo: PHM-SA)

According to Ruder, GLP-1 also has other effects that we are only beginning to understand, and the exact mechanism for weight loss is not yet completely understood.

“It delays the stomach from emptying too quickly. This means you stay full for a longer stretch of time, resulting in lower urges to snack. This also aids in the proper digestion of food. The other effect is that it enhances the efficacy of insulin. This results in lowered blood sugar, a decrease in blood pressure, and even reductions in levels of cholesterol,” he says.

“There is also some data to suggest that GLP-1 may improve the gut microbiome to a pattern that is more favourable to weight loss. We also think there is some other direct effect on fat because appetite alone does not explain the level of weight loss that we see,” he says.

Ruder said that research has found that, in obese diabetic patients, “the production of this hormone in response to a food load is suboptimal”.

“So, you give the patient more of this hormone from the outside to make up for the deficit. In obese patients, higher doses are required to get significant weight loss compared to those with type 2 diabetes.”

How well do they work?

“The weight loss is significant enough to make a clinical difference, in other words, to have a positive impact on health outcomes,” says Ruder.

“Losing 5 to 10% of body weight in addition to improved blood pressure or cholesterol is considered clinically significant. In obese diabetic patients, a 10 to 15% reduction in body mass can even put diabetes into remission in some cases.”

According to Andy Gray from the University of KwaZulu-Natal’s Division of Pharmacology, there are a number of GLP-1 agonists on the global market, including albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide and tirzepatide. Only four of these have been registered in South Africa.

Glucagon-like peptide-1 agonists (GLP-1) like Ozempic are a class of drugs initially developed for the treatment of type 2 diabetes, but have been shown to be highly effective for the treatment of obesity and being overweight. (Photo: FocalFoto)

However, only two products are appropriate for the treatment of obesity – the well-known semaglutide (brand name Ozempic) and liraglutide (brand name Saxenda).

The other two drugs have not been studied in people with obesity and, according to Ruder, it is unwise to prescribe them to patients for this purpose, although he has come across a handful of local doctors who do.

Semaglutide and liraglutide, on the other hand, have been studied in people with obesity and have been approved by many regulators for this indication. However, in South Africa, only Saxenda is approved for the treatment of obesity. Ozempic is only approved for diabetes treatment but is being widely prescribed on an off-label basis.

According to a 2022 study published in JAMA, a leading medical journal, after 68 weeks of taking the drugs, obese patients on semaglutide lost an average of 16% of their body weight compared with 6% for those taking liraglutide.

Side-effects

Although considered relatively safe, it is accepted that the benefit outweighs the risks in most cases as there are some side-effects and contraindications.

“The most common side-effects are nausea, indigestion and bloating. Less commonly, some patients experience severe vomiting and diarrhoea. This usually only lasts a few weeks before the patient develops a tolerance,” says Ruder.

This is why patients are started on low doses that are gradually increased over a couple of weeks or months.

“In very rare cases these drugs should not be prescribed to those at risk of a specific type of thyroid cancer and those at risk of pancreatitis and gallstones,” he says.

In terms of long-term side-effects, much less is known. Liraglutide was approved for weight loss in the US and Europe in 2014. Venter says one can take comfort in the fact that it has been on the market for 10 years and has been used by a large number of people. He says it is likely that any dangerous side-effects would have been picked up by now.

Semaglutide, however, was only officially approved for weight loss in 2021 by leading regulatory authorities. Ruder says clinicians should proceed with caution and patients should be closely monitored in the coming years in order to pick up on any unanticipated side-effects.

Obstacles to access

According to Venter, the drugs are “ludicrously expensive” and “continuously going out of stock”, which are massive hurdles to access.

Some have raised concerns that the injectable nature of these medications will be difficult for patients. Ozempic comes in the form of a once-weekly injection and Saxenda is a daily injectable – both need to be stored at a relatively low temperature, preferably in a fridge.

However, Venter says patients get used to injecting themselves in his experience.

Claire says she was “scared” to inject herself in the beginning, but after a couple of weeks, she has become completely comfortable with the process. Her father, who is also taking Ozempic, is “terrified of needles”. But even he has largely overcome this “psychological terror” to a large extent. But Claire still administers the injection for him.

Stockouts are a big problem in terms of access and, according to Ruder, have been fuelled by patients who are not diabetic or classified as obese or overweight, pressuring clinicians to prescribe Ozempic in particular for “vanity or cosmetic or simply aesthetic purposes”.

This scenario has come about, in part, because of the social media furore and celebrity endorsements of GLP-1 agonists which have created massive hype and demand.

“When considering pharmacotherapy, it should be to treat obesity as a disease. It is not intended for a person who wants to lose a few kilos before a wedding, for example. It is important,” according to Ruder, “to have a thorough consultation with patients before prescribing these medications to determine whether they are appropriate for clinical reasons, instead of giving them out to whoever happens to ask.”

Ruder says that local diabetic patients have been harmed by stockouts of Ozempic and have been forced to use inferior drugs at times.

Cost is the most glaring obstacle in terms of access for those living with obesity, as both drugs are still under patent in South Africa, according to Gray.

Depending on the dose, Ozempic can cost between R1,500 (minimum dose) and more than R6,000 (maximum dose) per month.

For Saxenda, patients can expect to pay between R2,500 and R4,000, depending on the dose.

The maximum dose per week of Ozempic for obesity is 2.4mg and 3mg for Saxenda.

However, according to Venter and Ruder, generic liraglutide is expected to be available locally within the next few years.

Unfortunately, this may not solve the problem of cost.

Venter says that without advocacy or creating some kind of pressure to bring costs down, it is unlikely that the price of new products will come down enough for the majority of people to afford.

“Often, with generics, they only drop the price a little, sometimes we only see a price drop of 30%,” he says.

Asked if this is enough to increase access in South Africa, he says: “Good heavens, no! R1,600 a month is still much too high for most.”

Is the high cost driven by production costs or simply by profit?

“The drug companies say there is no way to make these drugs cheaply, but they can, in fact, be made at a fraction of the cost and still provide handsome profits,” says Venter. He was involved with a study about the prices of anti-obesity medications that was published in February in the journal Obesity. The investigators found that manufacturers could still make a 10% profit with an almost 20-fold reduction in the current prices.

There are a number of GLP-1 agonists on the global market, including semaglutide (brand name Ozempic) and liraglutide (brand name Saxenda) that are appropriate for treating obesity. (Photo: Antefixus21 / Flickr)

Spotlight sent questions last week to Novo Nordisk, the manufacturer of Ozempic, including a question about pricing. The company indicated it would respond to the questions, but had not done so by the time of publication.

“We need a wave of activism to say enough is enough now. These companies should not be able to make obscene amounts of money off of these drugs at the expense of huge numbers of people,” Venter said.

According to Venter, advocacy is lacking when it comes to obesity because of the pervasive stigma that still exists.

“For me, obesity is the last great stigma. On the individual level, it’s terrible, even without other NCDs – there is a huge stigma attached to being obese. You are told it’s your fault. It feels a bit like HIV, bizarrely – brought on by yourself because you didn’t do x, y and z,” he says. “Unfortunately, access to these drugs is not seen as essential treatment but simply a vanity issue. This has to change if we have any hope of tackling the epidemic in any real way.”

Claire feels the stigma has followed her for decades.

“Eventually I got to a point where I don’t want to look in the mirror. I avoid it because when I see myself, I just imagine what everyone is thinking when they see me. Society is geared this way. To tell me I am wrong, I am lazy, I am gluttonous, I am weak, I have no self-control, I’m irresponsible. Over time I stopped doing more and more things thinking I’m too big to do this or to do that,” she says. “I know I am buying into the same rhetoric. It’s bad enough to deal with the world, but being constantly plagued by my own negative self-talk is soul-destroying.

“But I don’t feel like that with Ozempic. I’m not focusing on my weight all day. I wouldn’t describe it as a quick or easy way out, but it’s the first time I’ve been offered something that actually works for me,” she says. “You get to where you are for various reasons and you stay there for others. But it’s liberating to know that I’m not always going to be the big girl in the room.” DM/MC

NOTE: Professor Francois Venter is quoted in this article. Venter is a member of Spotlight’s Editorial Advisory Panel. The panel provides the Spotlight editors with advice and feedback on the quality and relevance of Spotlight’s public interest health journalism. The Spotlight editors, however, remain editorially independent and solely responsible for all editorial decisions. Read more about the role and purpose of the panel here.

This article was published by Spotlight – health journalism in the public interest.