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Health

Obesity doctors are finally beginning to understand how to

really treat the problem
Third-generation drugs can change people’s lives in the same way statins turned
heart disease on its head

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Treating obesity is important because of its complications, which include type 2 diabetes,
cardiovascular disease and several types of cancer

Professor Carel le Roux

November 15 2022 07:30 PM

At long last, the biology of the disease of obesity is being unravelled. This may
help the one in four people in Ireland who have obesity.

Treating the disease is important because of its devastating complications, which

include type 2 diabetes, cardiovascular disease and several cancers.

Previously, obesity was thought to be a disorder of willpower, resulting in people

living with obesity being stigmatised, very often by healthcare professionals who,
at the time, didn’t have access to the latest scientific evidence.

But as an obesity physician working in Ireland today, I have experienced first-

hand a revolution happening in the way we think about the disease of obesity and
how we treat it.

There is a risk that if we don’t get this right, we will move the field several steps
back, but we now have the scientific evidence we need to take several leaps
forward.

We now understand that hunger and fullness signals are generated in parts of the
brain that are not related to conscious awareness. Obesity is thus considered a
consequence of diseased areas of the brain that we cannot control by thinking.

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Researchers in Ireland, such as Professor Carel le Roux, are at the forefront of the revolution in
understanding obesity as their work, ranging from the laboratory to the research clinic, is now
focussed on understanding the disease better

So, we now consider obesity a neurological disease. This is especially clear when
we consider genetic disorders resulting in the loss of specific nerve functions in
the brain that can lead to severe obesity, especially in children.

Targeting the disease itself in the brain areas responsible for obesity by using
nutritional therapies, pharmacotherapy, or surgical therapies results in the
disease coming under control.

If the disease is controlled, then people naturally feel less hungry and fuller after
smaller meals. Ultimately this results in significant and sustained weight loss and
remarkable improvements in the quality of life.

Understanding how the disease of obesity causes harm in the brain allows a more
focused treatment approach to help people.

 A frequently asked question is whether these third-generation obesity


drugs will displace the need for bariatric surgery in Ireland
Researchers in Ireland are at the forefront of the revolution because their work, 
 
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ranging from the laboratory bench to the research clinic, is now focussedSubscribe
on
understanding the disease better.

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A major European Research project, IMI SOPHiA (www.imisophia.eu), is

coordinated from UCD to understand the predictors of risk of obesity and the
predictors of response to obesity treatments. The biggest advances are being
made with new drugs.

Third-generation medications for obesity are based on naturally occurring

hormones from the gut. The purpose of these hormones is to signal to the brain
when a person can feel satisfied enough to stop eating. These hormones are often
lower in people with obesity, so using these naturally signalling pathways can
address the disease at its origins.

Some of these third-generation medications are once-weekly injectable

treatments which have been approved as a treatment for obesity and or diabetes
by the Food and Drug Administration in the USA, Health Canada, the Medicines
and Healthcare Products Regulatory Agency in the UK, and most recently by The
European Medicines Agency.

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Third-generation medications for obesity are based on naturally occurring hormones from the
gut, the purpose of which is to signal to the brain when a person feels satisfied enough to stop
eating

The drugs appear to act on the dysfunctional nerves which cause obesity. Initially,
the medications stimulate fullness, reduce hunger and food intake, and ultimately
allow patients to maintain a body with less fat tissue. So, these medications should
be considered as a treatment for the disease of obesity rather than weight loss
drugs.

Ireland contributed to the Semaglutide Treatment Effect in People with Obesity

(Step) programme, an assembly of 15 international high quality trials. The patients
treated with the drug semaglutide lost 16pc more weight (13kg), while those on
the dummy drug with lifestyle treatment lost 2pc (3kg).

The drug also had health benefits, including improvements in inflammation,

cholesterol, blood sugar and blood pressure.

The safety of the drug was also similar to medications used to treat diseases such
as diabetes. Mild tummy symptoms were the most frequent complaint of patients.
The latest data emerging from this programme now show that semaglutide with
very minor lifestyle changes results in the same amount of weight loss as
semaglutide with the most intensive lifestyle changes.
Additionally, when semaglutide is used to treat children with obesity, the same 
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of weight loss is achieved as in adults. This really raises the question of
whether lifestyle changes are even needed for the benefits of the medication to be
realised.

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Professor Carel le Roux says obesity is considered a consequence of diseased areas of the brain
that we cannot control by thinking

The Surmount programme from Eli Lilly is another international programme

comparing the efficacy and safety of tirzepatide to a dummy drug in adults who
have obesity. The first of these studies reported average weight losses of
22pc (22kg) with a similar safety profile as semaglutide.

The drug is now approved for the treatment of diabetes but not yet for the
treatment of people who do not have diabetes.

The catch, however, is that these drugs treat the disease of obesity and when the
drugs are stopped the disease relapses, resulting in patients becoming hungry,
eating more food, and gaining weight. These drugs are thus not a cure for this
disease but rather an effective long-term treatment.

This reminds us of what happened when we started using statins to prevent

people having heart attacks. Statins today are among the most extensively
prescribed drugs universally, because they are well tolerated and have proven
benefits to reduce heart attacks and help people live longer.

Likewise, the third-generation drugs for obesity have the potential to transform
the field of obesity care and change the paradigms of managing obesity.
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Scientists now understand that hunger and fullness signals are generated in parts of the brain
that are not related to conscious awareness

A frequently asked question is whether these third-generation obesity drugs will

displace the need for bariatric surgery in Ireland, where only 1 in every 1000
people who is eligible to receive bariatric surgery receive the operations.

These third-generation obesity drugs are unlikely to be the preferred option for
these patients but are more likely to be prescribed to those who may not wish to
have surgery.

If the drugs penetrate only 100 in every 1000 people living with obesity, then
approximately 20 of these patients may have a suboptimal response.

Many of these patients may wish to escalate their therapy to include surgery. So, it
is likely that the total number of patients wanting surgery may increase tenfold in
the short term.

In a nutshell, third-generation obesity drugs are likely to revolutionise obesity

treatment in the same way statins impacted the treatment of heart disease.

These drugs are highly effective, likely to be well tolerated, and require very little
effort from patients or clinicians. Similar to statins, the hope is that the new
obesity drugs will allow patients to live longer with a better quality of life.

Professor Carel le Roux is an obesity specialist at St Vincent’s Healthcare

Group. He is a contributor to Future Island, which airs on RTÉ One & RTÉ
Player Tuesday, Wednesday and Thursday at 7pm all this week as part of
Science Week.

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