The Quest for a Weight-Loss Drug That Actually Works

Researchers and pharmaceutical companies have poured time and money into developing an effective drug to combat obesity. But time and again, the drugs have failed to deliver. In episode five of Prognosis, Bloomberg's James Paton talks to scientists on the cutting edge of weight-loss research, and the companies that may finally be close to finding a medical solution to the obesity crisis.

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Episode Transcript

Speaker 1 (00:03):
Two studies out today. They draw the same disturbing conclusion.
Americans are not winning their battle against obesity. One study
found that obesity raised for adults actually obesity. It seems
like it should be easy to treat calories in, calories out, simple,
but it's actually incredibly difficult. And that goes both for

(00:26):
the people who are trying to slim down and the
drugmakers who have struggled to find treatments to help. Welcome
to Prognosis, a podcast about health, medical technology, and the
mind blowing innovation underway across the globe. I'm your host,
Michelle fay Cortes. More than seven hundred million people around

(00:46):
the world are considered obese. If you're five ft eight
inches tall and way more than two hundred pounds, that's obese.
If you're shorter, say five ft four inches and more
than a hundred seventy five pounds, that's also obese. It's
about much more than how you look. It increases the
risk of diabetes, heart disease, and cancer, and it's expensive.

(01:09):
The health costs in the US alone top a hundred
and fifty billion dollars a year. If drug makers could
find a way to help people achieve safe and significant
weight loss, it would spur profound benefits, not to mention profits.
It hasn't happened yet. Every few years there is a
new hyped drug that seems to show up with outsized expectations,

(01:29):
but they've generally turned out to be disappointments. Some believe
that's about to change. Most people who succeed in losing
weight quickly gain it right back. Our bodies are programmed
to do that. Now, a promising new approach in the
lab aims to both suppress appetite and switch off the
signal that tells your slim down body to conserve energy.

(01:51):
That may be just the key to keeping those pounds off.
Here's Bloomberg's James Peyton with the story. To understand the
obesity crisis today, we need to start with some history.
Ancient history, like all the way back to the Stone
Age history. So let's rewind tens of thousands of years.

(02:15):
Humans are hunters and gatherers, and in order to survive
the cycles of feast and famine, they needed to consume
extra calories and hold onto them. Mad's CROs Guard Thompson,
the chief science Officer and Nova and orders the Danish
drug company puts it like this, so so we would
simply have a situation wherein the one half of the
year we would be really good at putting on a

(02:38):
lot of weight by eating a lot of food, and
then in the other half, the cold half of the year,
where the buffalo were no longer there to be hunted
and there were no vegetables and so on, we would
have a situation where where people would typically go into
their caves and basically just try to survive quite quite honestly,
and burn off as little energy as possible so that

(03:00):
they were still alive when the next spring would rise.
So those who were best at conserving energy and storing
fat endured the harsh winters and went on to reproduce.
Those famine beating genes are a problem for us today.
Matt says. Our unhealthy habits, combined with our genetic tendency
to hang onto calories, add up to a double whammy
a weight gain. Nowadays, we are living in a constant

(03:23):
feast situation. We're eating, eating, eating, and we're not exercising much.
So those very genes that were good for our survival,
that made those people survive with longer lives and have
more babies in the old days because they were good
at preserving energy and building fat stores in their bodies.
They are now at risk of obesity, type two diabetes,

(03:43):
and other conditions. So that's where we are now. Our
ancestors relied on storing fat to survive, but our current
lifestyle blows that out of proportion. It took society a
while to realize what was happening, though it's only within
the last few decades that scientists have come to understand
the biology behind obesity. Years ago, an increase in body

(04:05):
weight or obesity wasn't considered to be a disease. We
really didn't understand anything about weight regulating mechanisms. It was
thought to be purely a disorder of of willpower, that
people with obesity were lazy, they couldn't control themselves, and

(04:26):
therefore it wasn't something that was worthy of being treated
by a physician. Another important point is that the relationship
between obesity and other illnesses like diabetes, high blood pressure,
heart disease, sleep disorders was not understood at all. That's

(04:46):
Lewis Roney, a doctor and obesity specialist at wild Cornell
Medicine in New York. He started a weight Control Center.
There Now, groups such as the American Medical Association classified
obesity as a disease. The centers for Disease Control and
Prevention acknowledge that genes are a factor based on the
different ways people respond to an environment of high calorie food.

(05:08):
Although obesity is still often seen as a self inflicted condition,
there's a growing realization that its causes are more complex.
Louis is especially fascinated by how hard it is for
people to lose weight and keep it off. He suspects
that's because consuming too much fatty food can damage the
nerves that tell the brain how much fat is stored.

(05:31):
Faulty signals can trick the body into erroneously storing unnecessary amounts.
That explains why trying to shed pounds can be agonizing
for some patients. It's very frustrating for people trying to
lose weight. If if and I would challenge anyone who
doesn't think so to try to lose weight. You get hungry,
you think about food. You may wake up in the

(05:52):
middle of the night thinking about food. And in the
past people thought they were going crazy, that there was
something wrong with them, but now we know it's the
result of these physical changes in signaling that caused us
to occur. Six years ago, not a single state in
the US had an adult obesity rate above thirty that's

(06:14):
according to the CDC. Recent data show that seven states
have since moved into that danger zone. One is Louisiana,
where there's abundant fatty food, a lack of physical activity,
and all the other usual culprits. And now more regions
around the globe are starting to look like Louisiana. Eric
Rabson is an obesity expert who works at Pennington Biomedical

(06:36):
Research Center in Baton Rouge, the state's capital. Despite the warnings,
he says, many people simply don't comprehend the gravity of
the situation. It's like global warming. You know, what does
it take to be concerned? I mean, it takes these
climate disasters and all that, and we're going to face
the same when it comes to public health. Eric is

(06:59):
a former research or at pharma company Eli Lily, and
so he's well aware of the industry's long battle against
the condition. It's been a humbling experience for many of
the people pursuing a solution. The whole treatment of obesity
has been very disappointing, and this has been a train
wreck of failures. UH, and it started, you know, in

(07:21):
the nineteen thirties. Early products to tackle obesity included laxatives,
thyroid hormones and fetaments, and other drugs that came with
severe side effects. Similar approaches continued through the nineteen sixties.
Many of these products were pulled from the market. Then
in the nineteen nineties, researchers thought they had finally found

(07:41):
an answer. It was called fed fen, a weight loss
treatment that combined fin fleuramine, a nineteen seventies era diet drug,
with fentamine and appetite suppressant. The treatment became a huge success,
but the frenzy soon turned into a fiasco. Very early

(08:04):
we discovered that fan frew i mean, was causing heart
valve problems, and this was also withdrawn from the market. Personally,
I went to Eli Lily in the nineties late nineties
to work on obesiti drugs, and UH, at that time
there is a real hope that new drugs we're going

(08:25):
to target very specific receptors and being very efficacious, but
it didn't pan out. A high point that same decade
was the discovery of leptin, a hormone tied to hunger
When people at fat, leptin levels increase, telling the brain
that the body has had enough to eat. But leptin
also failed to live up to expectations. When researchers found

(08:47):
that many of these people were resistant to its effects,
several more dead ends followed. So why do scientists and
farming companies keep trying? Quite simply because an effective weight
loss drug would be among the holy Grail of meds,
right up there with treatments for cholesterol and arthritis. Novos

(09:08):
focused on a weight loss treatment dates back to the
nineteen nineties, so slightly more than twenty years ago. We
had a very philosophical discussion in the management of the
company whether obesity was a disease or a a lifestyle
driven condition, and we actually came to the conclusion that
it was not only a chronic diseased that was genetically predisposed,

(09:32):
it was also the precursor stage to diabetes. Lately, the
focus is on a hormone that plays a role in
regulating blood sugar and body weight. It's called glucagon like
peptide or g lp one, and it was first used
to treat diabetes. No Vo is now repurposing its new
diabetes drugs and relying on a synthetic version of the

(09:52):
hormone to mimic what's produced naturally in the body. This
work is at the core of the company's strategy to
develop a more effect of obesity treatment. The company developed
an injectable g LP one drug called Sassenda, designed to
make you feel less hungry. It's one of several available
today that deliver weight loss in the five to ten
percent range. But these drugs are expensive and the results

(10:16):
tend to stall after several months, prompting some patients to
stop taking them. Many insurers, employers, and governments are reluctant
to cover the cost, so no Vo is pushing the boundaries.
Its researchers are testing a next generation drug in the
same class, with hopes of getting closer to delivering fifteen
percent weight loss that's considered a kind of magical level

(10:38):
the drug companies figure they need to reach to really
open up the market. The company has just started a
late stage trial to evaluate the treatment's heart benefits in
more than seventeen thousand people. It's the largest study in
the company's history. Now, if Nova can show the medicine
extends lives, reducing heart attacks and strokes on top of

(10:58):
slashing weight will no doubt bolster the case for the
drug and help the company win over skeptics. But that
would be just step one. No Vo has bigger plans
in mind. It's betting on combinations of complementary hormones to
try to create a super drug that will overcome the
body's tendency to put the pounds back on after weight loss,

(11:19):
or in other words, fight our caveman like tendencies. It's
a radical approach and ambitious weight loss north of tent
or even more. To get there. No those scientists will
have to attain results comparable to gastric bypass and other
weight loss surgeries, but the idea is that the treatments

(11:41):
won't have the risks and complications such as blood clots
and infections that can occur with those major operations. No
Vo has been able to extend the impact of an
appetite regulating hormone called ammlin by boosting its half life.
It was just a few minutes, now it's about one week.
Early studies suggest that increasing the amount of time it

(12:03):
circulates in the body could enable weight loss of roughly
one percent every seven days. And the good news is
that this is an effect that seems to be additive
to what we know from GLP one. So if you
actually add the two compounds together, you get twice as
much if you can see twice as much bank for
the box, so to speak. This is often what human

(12:23):
beings need because if you don't deal the system and
one to blow, so to speak, then there will be
compensation compensatory mechanisms that are kicking in to try to
regain the body weight. So we believe to real large
extent that combination therapist will be a good way forward
for people with the cbobt ma's. This team is working

(12:44):
hard to come up with drug combinations that boost the
amount of energy the body burns while it's the same
time suppressing appetite that takes us to mitochondria. Mitochondria, you
may recall from your high school biology class, are those
any structures inside cells that, among other things, converted sugars
into energy. Nov researchers are looking at ways to stimulate

(13:08):
energy expenditure in a way that doesn't affect heart rate
and blood pressure, a feat that others have tried but
failed to pull off safely. Eric, the researcher in Louisiana
recognizes how beneficial that could be. He studied contestants from
the reality TV show The Biggest Loser. Previously on The
Biggest Loser at the Way in the red en Blute

(13:30):
had disappointing numbers. We have to reassess what is going
on because sometimes gotta changshing. The contestants metabolism slowed dramatically
after shedding significant amounts of weight, and many of the
Biggest Losers regained a lot of the weight they had dropped.
Eric realized the importance of somehow keeping energy expenditure up.
After someone sheds pounds, Let's say you lose ten percent

(13:53):
of your weight, you have a decrease in your resting
metabolic rate, which is going to be more than ten percent.
We did studies in the Biggest Loser who lose up
to half of their body weight, and these people become
tremendously energy efficient. In other words, they have a very
very low metabolic create. And I believe that in the

(14:16):
first phase of treatment in appetite suppression, drug is the
most adequate way to go. But after reaching a plateau
let's say five, ten or even fifteen percent weight loss,
you need to introduce something else which is going to

(14:36):
boost up your energy metabolism. One mixture of drugs won't
work for everyone, and scientists are seeking to understand why
Eric is optimistic. They will thread the needle. I have
heard many times, you know, within ten years will have
this magic pill or whatever. And and now I've I'm

(14:58):
wise enough not to say that at but I know
we are making progress, and these progress are important, and
I think that eventually, yes, we will be more successful
in treating people. No Vo isn't the only entity trying
to better understand that rate at which the body converts
food to energy. Scientists at a number of universities are

(15:19):
finding answers that reside inside the brain. Rachel Lippert was
previously involved in studies in mice at Vanderbilt and the
University of Michigan. She studied the function of a brain
protein called m C three R and how it helps
balance the amount of energy we take in and use.
The workings of m C three R have long baffled scientists,

(15:40):
and a better understanding of the protein may open up
a new path towards obesity drugs. Rachel now works at
the Max Planck Institute for Metabolism Research, in Germany. She
says epigenetics, the study of how genes are turned on
or off by factors in the environment, are also providing
new clues. There's so many layers of complex city that
have been discovered recently because of all of the advancement

(16:04):
and genetic tools that we have in the basic research laboratories.
That is really just kind of it's like peeling back
layers of an onion in terms of the levels of
complexity that we deal with in the basic research. Because
obesity leads to so many other serious diseases, the potential
impact from an ultra effective drug could have a big

(16:26):
ripple effect on patients and help governments all over the
world deal with the obesity crisis. So just imagine that
you take the medicine, you lose the weight, and you
don't have to take something for your pre diabetes or
your blood pressure or your cholesterol, and your sleep disorder
gets better. You know, that is the promise of obesity treatment.

(16:46):
I joke around with our younger doctors and tell them
it's like one of those late night infomercials where you
get the miracle knives, and you get the friar and
you get every thing thrown into one. When you treat
the obesity, you get all the health benefits. Still, there
are plenty of naysayers out there. They say the focus

(17:09):
should be on preventing obesity, not treating it, and they
question whether drugs should be part of the strategy at all.
Others want to tax products such as sodas to really
make a difference. Lewis says he's even gotten pushed back
from some of his own colleagues. As many resources as
we can we should apply to preventing obesity, but the

(17:31):
fact is that once obesity is established, using strategies to
prevent obesity don't work. They're not enough. It's kind of
like someone's diagnosed with lung cancer and you tell them, Okay,
you have lung cancer now, and your treatment is going
to be to stop smoking. Right. That sounds absurd, but

(17:55):
trying to prevent the disease once it's established doesn't usually
work as a therapy because something physical has changed. For now,
few doctors and patients are relying on medicines to treat obesity. Diet, exercise,
and other changes are vital, but if those measures don't work,
some people should be treated with drugs before their situation

(18:17):
gets worse before they develop diabetes and other complications. That's
the view of experts, including Lewis. He believes more patients
will get drugs in the future as the science and
awareness among physicians accelerates. An Obesity board set up seven
years ago in the US certified more than six hundred
doctors in the past year. He says, that's comparable to

(18:39):
the branch of medicine focused on the digestive system and
its disorders. So these drugs are playing a limited role
right now. Are we at any kind of turning point?
Do you think when it comes to the treatment of
obesity with medicine. I can't tell you when the turning

(18:59):
point will come where there's widespread adoption of medical therapies
for obesity, but I strongly believe that it is coming,
and I'm not sure we're going to be able to
change the course of the obesity epidemic and the health

(19:23):
complications through behavioral management alone. While it's hard to know
when that might happen, researchers at least have a roadmap.
Two decades ago, Matt says type two diabetes was as
misunderstood as obesity is today, but that changed when scientists
showed controlling blood sugar levels would extend lives and lower

(19:46):
hearts and stroke risks. I do believe that we are
now standing at the inflection point where obesity in the
next few years to come will undergo the same you
can say, mitamaphosis from being considered a life style disorder
to being considered a serious chronic disease. And part of
that job is for us to do the studies I'm
discussing and and proving to society, just like we did

(20:09):
with diabetes twenty years ago, that this is the case,
and that will then drive rational uptake of of of
new therapists in that marketplace, giving people a healthier and
a longer life. We hope it's a new era for
obesity drugs. Novo is developing treatments that act like natural
hormones to try to avoid the bad side effects see
in the medicines the past that affected the central nervous system.

(20:32):
The company is also learning more about the hormones that
allow the stomach and the brain to talk to each other,
what he calls the gut brain access. I think combinations
of these mediators that exist in the so called dialogue
between the gut and the brain. They will be very
important to investigate, and also the ability to co administer

(20:54):
them so that you actually get maybe one, maybe two,
or maybe even through red signals that either signal society
or increase the energy expenditure. Mad says sometime in the
distant future, we may evolve in a different way, become
better at burning off energy and consuming less. For now,

(21:14):
Novo wants to help patients fight their inner caveman. I'm
quite optimistic that ten years from now, if people um
are actually treated, they will have longer and better lives.
And this is not wishful thinking. This is based on
clinical evidence that we're creating as we speak. And that's

(21:41):
it for this week's prognosis. Thanks for listening. Do you
have a story about help here in the US or
around the world, We want to hear from you. You
can email me at m Cortes at Bloomberg dot net
or find me on Twitter at the Cortes. If you
were a fan of this episode, please take a moment
to rate and review us. It helps new centers find
the show. This episode was produced by Lindsay Craterwell. Our

(22:05):
story editor was Rick Shine. Thanks also to Drew Armstrong
francesco Leavie is head of Bloomberg Podcasts. We'll see you
next week.