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Tackling obesity with medication: New hope and real challenges

- Wits University

Pharmaceuticals could be manufactured and sold at reasonable profit, far below the current eye-watering prices, according to a paper in the journal Obesity.

Using similar methods to those used for HIV antiretrovirals, this study showed that it’s possible for patients to be able to access life-saving therapies while pharmaceutical companies can profit fairly and ensure sustainability.

Authors on the paper have used similar methods to show the same outcome for hepatitis C and drug-resistant tuberculosis (TB) therapies.

It’s no small deal.

The Southern African region is in the midst of a complex obesity epidemic, that probably includes an interplay of a rapidly changing diet driven by an aggressive processed food industry, and a genetic hand that predisposes to obesity.

Of the South Africans over the age of 15 years, 41% of women and 11% men were reported to have ‘obesity’ – an imprecise but usable definition of being overweight at a population level –  in the 2016 South African Demographic and Health Survey. And it’s only getting worse.

But we are HIV researchers. How on earth did we get into obesity?

In 2019, our team at Ezintsha, a division of the Wits Health Consortium, published one of the most important HIV antiretroviral treatment studies of recent times. The study, called ADVANCE, compared new HIV regimens against the then gold standard.

As expected, we showed that the new regimens were very safe and worked better than the gold standard.

Unexpectedly, we demonstrated a remarkable and very worrying rise in weight.

A long and complicated story short: the old drugs were masking this weight gain, and our HIV positive patients, recruited in central Joburg, were suddenly gaining weight – just as the general population were – on the new regimens.

It is not entirely clear whether the new drugs, or even HIV, may be playing a role in this weight gain but what was clear was that our participants on ADVANCE had a real problem.

We pivoted to what we were taught at medical school – ‘lifestyle changes, move more and eat less.’ We dispensed dietary advice – which is difficult to follow when you live in central Joburg and can’t afford expensive organic ‘healthy’ food. We advised exercise – also a bit presumptuous, as colleagues in Physiology at Wits had done actigraphy tests on some of the participants, and many would make the Discovery 10 000 steps targets proud, but they gained weight anyway. (Actigraphy is a non-invasive method of monitoring human rest/activity cycle).

Participants began to complain about the cost of replacing their entire wardrobe. One participant hit a body mass index (BMI) of 60 despite all the lifestyle help (a ‘normal’ BMI is below 25). BMIs are not a great single marker of health, but at the more extreme, in the 35-40 zone, they start being associated with poorer health outcomes including diabetes, problematic pregnancies and some cancers.

Another participant broke down in tears in the clinic: “I keep doing what you tell me, but it is not working. Why can’t you help me?”

Why indeed?

Mostly because what we were taught at medical school in the ‘80s and’ 90s about deliberately losing weight was not helpful.

The results of ADVANCE forced us out of our HIV bubble and into a new world of weight physiology, exciting new treatments, and even new non-stigmatising language around obesity.

We learned that exercise and dieting only occasionally achieve sustainable weight loss. Make no mistake, eating properly and being active is very, very important for good health. But it won’t make you lose weight, except in the very short term, other than in a small percentage of people.

Weight is like a thermostat; the body is constantly trying to reset to a set weight it considers ‘normal’, often through increasing hunger – and that set point can only go up. Remarkably, and depressingly, the only reliable thing that leads to sustained weight loss is bariatric surgery and the currently expensive medications discussed in the Obesity paper.

We began to dispense these medications to our patients (those who would afford them), under the watch of an experienced Wits endocrinologist. All the medications suppress appetite, thereby fooling the ‘set point’. Some medications are oral, often taken twice daily; some are injectable, either taken daily or weekly, depending on what you can afford or on stock availability. They are all very fiddly, most needing the dose to be slowly increased, which requires a health worker nearby. All the medications have minor side effects and need monitoring; serious stuff is rare, although experience with the very new agents is limited.

Results are pretty predictable and amazing! Every person that we have treated who tolerated the drugs, including lots of HIV negative people, have lost significant weight. The clinical trial reports vary – from about 7% to as much as 20% weight loss in just over a year. Regrettably, if you stop the medication, weight steadily comes back, just as what happens with high blood pressure and diabetes medication, so people with obesity may be on some form of these drugs permanently.

It feels like we are back to HIV in the year 2000: We have a condition affecting millions of South Africans that has stigma and prejudice attached to it. We have a complex therapy that is hopelessly and unjustifiably unaffordable. And we have medical aids that won’t pay for it, and governments with no plans for it. Yet again, activist organisations like the HEALA coalition and Wits’ Centre for Health Economics and Decision Science (PRICELESS-SA) are wading in to take on the sugar and food industries, which don’t want labels on what you are eating.

But the reality is that people living with obesity have no options unless they have deep pockets and a switched-on doctor.

Of course, countless unanswered questions remain. What is actually a healthy weight? Can we address weight loss for health without reinforcing weight stigma? Are we playing into weight-obsessive behaviour with a medication-prone approach? What about long-term side effects? What are we doing about better food security in tandem? Can we make dosing simpler? Can we get more data in local populations? What about safety in pregnancy? The list goes on.

The good news is that we are starting to gain traction. Now we need to get firmly behind two clear areas: prevention legislation and programmes that gets healthier food to the population at a lower price, as well as treatment option into local clinics.

We also need a broad-ranging activist movement that gets angry at all the things the galvanized the HIV movement – inequity, stigma, inaction. The science has made a start, we need everyone else to catch up.

Dr Nomathemba Chandiwana, Dr Simiso Sokhela, Professor Francois Venter, Ezintsha, Faculty of Health Sciences, University of the Witwatersrand