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Good afternoon.
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I'm Jonathan Weber, and I welcome you to the latest webinar from the Cumbria Med Research Webinar Series.
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We're a collaboration of the new Pears Cumbria School of Medicine in Cumbria with our partners,
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Imperial College London, the University of Cumbria, and North Cumbria Integrated Care and HS Trust, NCIC.
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And we aim to bring webinars on aspects of importance and topicality in medical research,
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bringing experts from Imperial College together with local practitioners in Cumbria to talk about those aspects of medicine
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which we believe are important to all of us here. So welcome.
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So without further ado, I'd like to introduce our first speaker today on obesity,
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and that's Professor Tricia Tan from Imperial College London.
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She is a professor of endocrinology and also a consultant physician in endocrinology at Imperial College Healthcare NHS Trust,
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and was part of the group led by her mentor Steve Bloom,
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who really first identified some of the actions of the GLP -1 agonist on obesity.
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Tricia, over to you.
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Hi, Jonathan.
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Thanks for this kind invite.
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And I'm going to get straight to the talk.
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Let's just get this out.
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So just to check, can everyone see this?
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Yeah, we can see the slides.
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You can see the slides.
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Brilliant.
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Okay.
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Well, first, thanks for the kind introduction.
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I'm going to talk to you today about actions of GLP -1 on appetite.
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And I'm sure everyone, you know, has heard about all the drugs that are currently available with Govis and Tazepatide.
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And I hope today's talk, we will cover a little bit on the background, starting first on why we treat obesity,
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where pharmacological treatment fits in.
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I will give you a brief review on GLP -1 and its development,
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some clinical evidence for their use in obesity and associated conditions,
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and then just a little bit about future drugs on the horizon.
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so why do we want to treat obesity well one in four adults in the uk are obese
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and obesity we now know are associated with multiple comorbidities
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and we've listed over 200 plus the common ones include diabetes
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fatty liver disease heart disease high blood pressure arthritis obstructive sleep apnea associated with anxiety, depression, and cancer.
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So if you look at this person, the well -known person on the right, he had obesity, died at the age of 55,
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had edema, likely due to heart failure, leg ulcers, chronic ulceration infections, and likely to have been diabetic.
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He also had disability and was not able to walk or stand.
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So obesity is not a cosmetic problem.
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It is disabling and causes premature death.
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For many years, we have only had lifestyle and diet,
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which essentially leads to around 3 % to 8 % weight loss.
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But the problem we have is that with diet and lifestyle, it's often not sustainable.
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And then we see this yo -yoing of the weight over time.
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Then on the other spectrum we had bariatric surgery which remains very effective.
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It's a procedure that leads to long -term sustained weight loss
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and improvement in diabetes but it is really not a treatment option for everyone.
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And then what how about in between?
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Well for many years we didn't really have anything.
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We had olistat which you have led to only maybe 2 -3 % weight loss, but with lots of side effects.
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Since the development of GLP -1 agents,
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we now have drugs that actually can bridge this gap between lifestyle and surgery.
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And we're going to talk a little bit more about this.
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GLP -1 is a hormone that is secreted from our gut, from the L cells, and it's secreted after eating.
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Our gut will sense the nutrients, and the hormone secreted from our gut then signals to different areas,
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including the pancreas, the beta cells, to stimulate insulin release, and this brings blood sugars down.
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It also counter -regulates other hormones, such as glucagon, which is known to push blood sugars up.
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And the GLP -1 can also act directly on the appetite centers in the brain.
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So this therefore then triggers fullness and reduction in appetite.
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As I mentioned, this is a naturally occurring hormone.
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And the hormone itself that secreted only last for a few minutes in circulation.
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So what pharma companies have done over the last 20 years is that they have engineered and re -engineered the hormones.
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The hormones made up of, it's a peptide hormone, so made up of natural amino acids, so making it more resistant to break down by enzymes,
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and also adding something like a fatty acid tail here.
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And you can see this is semaglutide and tizepatide, where this then prolongs the half -life of the drugs.
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So now we're on to basically the third generations of these drugs.
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And the drugs can be given as injections and tablets.
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GLP -1, we have all been talking about this for the last year or so,
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lots in the media, but actually it's been around for 20 years.
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We've been using this to treat patients with type 2 diabetes
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and due to its beneficial effects of increasing insulin secretion and suppressing glucagon secretion.
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And on average, it's been shown to be effective in reducing the HbA1c,
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which is a way that we monitor the long -term control of diabetes by 1 .4 to 2 .1%,
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and also has the advantage over drugs like insulin and the sulfonylureas without significant hypoglycemia risk,
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so low blood sugars.
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But when used for treating people with type 2 diabetes,
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on average, we only see around five plus kilogram weight loss with the diabetes doses of the drug.
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But we have shown clear benefits in type 2 diabetes for cardiovascular disease,
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chronic kidney disease, heart failure, and stroke prevention.
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So this data has been generated for many years now.
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And examples of the earlier GLP ones includes exanatide,
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dulaglutide, but now more commonly people are using semaglutide or otherwise known as azempic, and also the oral version, which is ribelsius.
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And all these drugs for diabetes have been recommended.
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by NICE and other guidelines for treatment of diabetes,
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particularly for atherosclerotic patients with atherosclerotic cardiovascular disease and chronic kidney disease.
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How about obesity?
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Well, the trials really came out in the last six to seven years,
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And I'm going to now just take you through some of the key trials on the newer generations of GLP -1.
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Semaglutide, which is also used for type 2 diabetes, but known as a Zempic, but when used for treating obesity,
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it's called Wigovi, but they're the same drugs.
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For diabetes, we use one milligram weekly, but for the treatment of obesity,
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we use 2 .4 milligrams weekly.
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So basically, over the years, the trials have escalated the dose of the GLP -1.
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And you can see here that inpatients living with obesity but without diabetes,
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we achieved much better weight loss of around 15 kilograms over 68 weeks.
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How about tazepatide?
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Well, tazepatide, the same, initially licensed for treating diabetes, now also licensed for obesity.
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SUMOUT -1 trial is one of the pivotal trials.
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Tazepatide is a GLP -1 agent, but it is also a dual agonist.
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So it basically not just acts on the GLP -1 receptor, but it also acts on the GIP receptor,
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which is also an incretin hormone.
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GIP is also released naturally from the gut together with GLP -1.
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So it's thought to have a double action and the double actions thought to increase insulin secretion after eating.
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So technically targeting better glucose control and possibly also better appetite suppression.
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But the thing about GIP is that there's some interesting biology, which we still don't fully understand.
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But the thinking is that it has effects on our fat tissue,
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our adipocytes, increasing the breakdown of the fats and hence also improving glucose and fat clearance.
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And you can see here from the Surmount -1 trial that the terzepatite at around 68 weeks,
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you know, results in about 20 percent weight loss.
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And the extension study over three years have shown that if you stay on the high dose,
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you continue to maintain this weight loss over three years.
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And what's also really important here is if you look at the graph down here,
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if you are on the drug and you have pre -diabetes or risk of development,
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diabetes will very much suppress the development of diabetes from 15 % in placebo towards 1 % to 2 % over time.
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and um surmount five trial it's a trial
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that uh came out a few months ago essentially
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it's a head -to -head trial of tezapatide at its top
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dose 10 to 15 milligrams versus semaglutide 2 .4 milligrams
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and this essentially shows that tezapatide uh can achieve around six percent better weight loss than Wigovi or semaglutide.
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But Novonordis, who develops semaglutide,
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then came back with a higher dose study, what they call the step -up trial,
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where they then showed that actually if you increase the semaglutide dose to 7 .2 milligrams,
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you can also achieve even better weight loss with an additional approximately 3 % weight loss.
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So that essentially covers the weight loss side.
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But when we look at these drugs, we need to be thinking about other goals apart from weight loss.
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And there are many trials that have explored this, and I won't have time to go through them,
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but here is a table that essentially summarizes some of the benefits of GLP -1 outside weight loss.
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And this is a summary of randomized controlled trials.
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You can see here that there's now trial data showing improvements in diabetes, prevention of development of diabetes in people with pre -diabetes,
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cardiovascular disease, heart failure, fatty liver disease, chronic kidney disease, obstructive sleep apnea, and even peripheral vascular disease.
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I will now take you through some of these key trials, just highlighting some of the key findings.
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So the select randomized controlled trial essentially is a trial using semaglutide 2 .4 milligrams in patients living with obesity
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and with pre -existing cardiovascular disease, a study over four years.
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And this study showed over 20 % reduction in major adverse cardiovascular endpoints,
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which is very exciting.
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And you can see here also on the graph on the right
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that the primary cardiovascular composite endpoint curves actually separates very early on within three to six months of being on the drug.
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So even before we achieve significant weight loss.
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And to also compare the SELECT trial to the STEP1 trial, which was the obesity trial,
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patients in the SELECT trial only lost on average about 10 % weight loss so indicating here that there are
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weight loss independent mechanisms that is happening here with the use of these drugs.
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And as you can see on this list here on the left -hand side, it's not only reduced mace, but also all -cause death,
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development of kidney disease, development of diabetes, and risk of heart failure hospitalization and urgent visits.
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the mechanisms that you know
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that it's currently sort of being postulated behind some of these
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benefits is sort of multiple sort of contributions really from amelioration of high glucose to reduction in postprandial hyperlipidemia
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because the drugs also lead to reduction in chylomicron assembly in the gut.
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And if you have a dual agent with the GIP, there's a reduction in adipose uptake of lipids.
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The GLP -1 also leads to reduction in inflammation, which are drivers of atherosclerosis.
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And there is also a direct effect on myocardium leading to protection from ischemia.
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And at the same time,
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there is also a natriotic effect of the drugs leading to diuresis and contribution to reduction in blood pressure.
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But not to forget, with the reduction in weight, patients also become more active and more mobile.
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And this also leads to better health outcomes.
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So moving on, we will now talk a little bit about fatty liver disease, otherwise known as MASL or MASH,
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and both semaglutide
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and tazepatide have been trialed in patients with biopsy -confirmed metabolic dysfunction associated steatohepatitis
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and fibrosis stage 2 and 3 versus placebo -controlled.
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And both trials basically have shown resolution of the steatohepatitis and without worsening of the liver fibrosis,
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and also evidence of improvement in liver fibrosis.
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So this is very exciting.
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And from the heart failure perspective,
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again, both drugs have been assessed in patients with heart failure with preserved ejection fraction.
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And as you can see here, both led to improvement in symptoms,
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symptom scores, and tazepatide also showed a reduction in the adjudicated death from CV disease.
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Moving on to obstructive sleep apnea.
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Well, I've just highlighted this trial here, which is from Tizapati.
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Again, significant improvement in obstructive sleep apnea symptom scores.
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And there's also been similar study data for other GLP -1 agents, but they're much smaller study,
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so I've not highlighted it.
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So there is an overall class effect.
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In terms of chronic kidney disease, well, we're still awaiting definitive trials in the non -diabetic people with obesity.
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But these trials here, the FLOW trial, essentially is a trial in patients with diabetes,
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have shown favorable effects on composite kidney outcomes, onset of kidney failure, greater than 50 % reduction in EGFR,
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death from kidney -related OCV causes.
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And this is, as mentioned, in the context of type 2 diabetes and CKD2 and 3 and microalbuminuria. And equally,
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the post hoc analysis of the SELECT trial also demonstrated favorable effects in kidney outcomes in people without type 2 diabetes.
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So to round this off, I think I just wanted to talk a little bit about
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sort of the weight loss effects versus the direct effects of these drugs.
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And it's often difficult, but it's something that we need to think about when we start using these drugs in the clinic,
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because it may not always be due to the weight loss benefits as shown in the SELECT trial.
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And Navid Sitar and all put together this paper,
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which essentially tried to weigh out whether it's a weight loss effect,
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which we think is related to reduction in fat mass, mechanical loading, versus the direct effects on organs,
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where, for instance, leading to increased insulin secretion, anti -inflammatory effects, endothelial effects, reduction in lipids, reduction in blood pressure,
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etc. So if we go back to the comorbidities that we discussed,
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the conditions where we think weight loss has bigger benefits versus direct effects include things like joint problems,
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osteoarthritis, obstructive sleep apnea, fatty liver disease,
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hypertension, and heart failure versus the conditions where you've got atherosclerotic cardiovascular disease
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and type 2 diabetes the thinking is that there's more to it than just weight loss.
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There's a direct benefit.
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And something like CKD, we think more of a balance effect.
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And certainly this is something to think about a little bit more in terms of when considering treatments for these patients.
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So I hope I've given you a quick overview on the broad use of these drugs.
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I'm now going to just quickly take you through what else is on the horizon.
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So multi -agonist hormone as a treatment strategy is something that is currently the next exciting thing,
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really, and basically using GLP -1 as a backbone.
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OK, and this essentially is something that actually at Imperial we've been working on for many years.
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And we've done sort of many experimental human studies where we've shown that combining hormones,
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this actually results to not one plus one benefit, but actually synergistic effect.
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And if you look at bariatric surgery as a model, you can see that post -bariatric surgery,
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patients secrete three to four times higher levels of combinations of these gut hormones.
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So using those principles, we've shown that combining, for instance, GLP -1 and glucagon,
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this not only leads to reduction in food intake, you get more reduction than when using a single hormone,
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but you also get an increase in energy expenditure.
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And this is important because when we lose weight, we metabolically adapt.
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So how you burn energy drops.
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But if you have a drug that can then keep that energy expenditure at a good level,
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it can actually prevent the more rapid weight regain.
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So these are the principles that I think the next generation combination hormones will be thinking about.
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And here are just some examples of some of the combination studies that we've shown.
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And with the human studies that we've done, it essentially has shown that multi -agonism is an acceptable strategy.
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So what's on the horizon?
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Well, first, the GLP -1 plus glucagon is very much sort of close to becoming licensed and available.
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Quite a few early development of these combination drugs I'd like to also mention have discontinued,
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but these are the drugs that are currently still in place,
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suvidutide and mastutide, sort of completed or in phase three phase.
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And actually, in fact, mastutide is now approved for use in China.
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And the idea behind here, as mentioned, is synergistic appetite suppression, increased energy expenditure.
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And the other thing to mention is having glucagon on board means there's a direct effect on fat clearance in the liver.
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Retrotrutide, which is an Eli Lilly compound, is actually very exciting.
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It combines GLP -1, glucagon, and GIP.
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And the data to date shows that it's achieving even better weight loss than to zapatite,
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up to 24 % over 48 weeks in people with obesity.
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And in people with diabetes, more than 2 % drop in HbA1c,
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which is quite significant, and also improved weight loss over the other trials, about 17 % reduction.
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Prisha, I need to encourage you to wind up.
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To wind up?
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Okay, will do.
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So the next is just to mention, there's also GLP -1 plus amylin.
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Again, exciting combinations.
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So combinations, so far, preliminary data showing better weight loss.
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This other drug here is a GLP -1 and GIP antagonist,
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okay, and extremely sort of confusing, really, within the field.
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But again, you know, all that agonist and antagonist both working as well
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and certainly it's something
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that in the field lots of people including us at imperial are trying to unpick
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but here this drug here is interesting because you may be able to use this once monthly
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okay and then of course there are the oral agents ribelsius semaglutide but for obesity you'd be higher dose, 50 milligrams versus diabetes.
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And Ophaglipron is a small molecule.
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So it's not peptide based.
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It's easier to take.
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And data as shown here, you know, fairly good weight loss, you know, not as good as injections, but good enough.
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Okay.
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So I think just to sum up, These drugs are exciting.
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They do have side effects, but we know that the side effects can gradually reduce over time,
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and there are ways that you can mitigate this by slower dosing
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and slower dose escalations but real world data have shown
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that adherence is low so more than 50 percent people using database study mainly us
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and outside uk data have shown
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that more than 50 percent people discontinue treatment after a year
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but i think this could reflect either side effects or the fact
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that the drugs are expensive
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and people are having to pay for this in the uk unfortunately it's sad to say
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that there's inequality of access okay very few people in the nhs currently can access
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and people who can access the treatment
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you know need to be able to afford between three to five hundred pounds per month
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and to summarize we have these very effective drugs in use they're exciting.
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I hope I've shown you that these drugs bring many benefits,
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but in the long run they make no good if we're not able to use these drugs for people living with obesity.
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Obesity is clearly recognized as a key driver of multiple morbidity
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and we need to have proper funding
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and treatment for these drugs uh to be prioritized thank you sorry
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if i overran thank you trisha
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so without further ado i'm going to introduce dr ashara ranatunga from ncic based down in white haven
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at uh west cumberland hospital dr ranatunga hi yes
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okay so um thank you for the kind introduction
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and i will be talking about obesity is it the next pandemic
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and the role of a tier 3 weight management service today this is my topic outline
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and when we are talking about obesity it is important
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that we understand the scale of the issue what is obesity who is affected and what are the complications of the disease
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Obesity is a complex relapsing condition with multiple causes and significant implications for health.
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It has health implications at every stage across the life course from pregnancy through to childhood and adulthood.
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And as my colleague mentioned, living with obesity increases the risk of developing chronic diseases, including type 2 diabetes, heart disease,
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many cancers, liver and respiratory diseases.
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So, this is the prevalence of overweight and obesity data from the Health Survey for England 2021.
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You can see almost 6 out of 10 women and 7 out of 10 men were having overweight and obesity.
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And if we only look at the obesity data, 3 out of 10 women and 2 out of 10 men were living with obesity.
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This is the distribution according to gender, on the top graph you can see the women, and on the bottom graph you can see the men,
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so according to the age distribution as well, and again you can see starting from early adulthood up until late adulthood,
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the prevalence of both overweight and obesity is quite high, indicating that it has affected the working population,
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in turn affecting the productivity of the country.
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This is the prevalence of obesity on the top graph
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and prevalence of overweight and obesity on the bottom graph according to the year.
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So you can see again it has gradually increased over time.
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This is the prevalence of overweight and obesity according to the geographical distribution
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and you can see living in north of England we have very high prevalence of both overweight and obesity.
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Before talking about the management of obesity, it is important to understand the etiology of obesity.
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It is a complex multifactorial disease which has a complex interplay between many factors,
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biological, behavioral and environmental.
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Biological factors such as genetics, brain gut axis which is the communication between the brain and the intestinal tract,
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prenatal determinants such as pre -pregnancy weight of the mother and the maternal weight gain during pregnancy,
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stages of our life such as pregnancy, menopause, hormonal conditions such as underactive thyroid,
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Cushing's disease, certain medications such as antidepressants,
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antipsychotics, physical disability, gut microbiome and certain viruses such as adenoviruses can lead to weight gain.
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Behavioral factors such as excessive calorie intake, eating patterns, sedentary lifestyle, reduced physical activity,
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insufficient sleep and smoking cessation are some of the factors that can contribute to weight.
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Environmental factors such as food abundance,
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built environment is the environment which has component of social and physical determinants,
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socio -economic status, cultural factors, bias and discrimination and certain environmental chemicals can also lead to weight gain.
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As we all as we discussed before obesity is associated with multiple metabolic conditions.
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In this graph I have summarized that
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so you can see due to accumulation of fat tissue there's release of certain chemicals including inflammatory adipokines,
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cytokines and chemokines which in turn lead to vascular endothelium dysfunction which can lead to diseases such as hypertension,
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fatty liver disease and type 2 diabetes.
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With further progression of the disease there's development of chronic kidney disease and cardiovascular disease and beyond that some cancers.
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before
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when we are discussing about the management of obesity as we discussed before the disease itself is multifactorial in origin
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so it is important that we approach the management in a multidisciplinary manner
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so exercise both resistant training
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and aerobic exercise can lead to a fat tissue loss dietary changes such as low carbohydrate diet low fat diet
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and high fiber diet can lead to weight loss.
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Bariatric surgery procedures such as gastric banding,
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gastric bypass, duodenal switch and sleeve gastrectomy can lead to weight loss by reducing energy intake,
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by altering gut hormones and gut microbiota.
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Healthy gut microbiota can also lead to weight loss.
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The ways that we can modify that is by changing our dietary habits, by doing physical exercise and undergoing bariatric surgery,
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consumption of prebiotic, symbiotic and probiotics.
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Psychological management also plays a key part including behavioral therapy.
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It is important in weight loss as well as maintaining the lost weight.
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With regard to the weight loss medications my colleague explained in detail the available options
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and how they work and future treatment options such as micro RNA might have a place in the future.
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So these are the available anti -obesity medications we discussed about liraglutide,
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semaglutide and tersepatide which is the newest medication that is available for us.
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Coming into weight management services, what are weight management services?
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They are multi -component programs that aim to reduce a person's energy intake,
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improve their dietary health and help them to be more physically active by changing their behavior.
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There are different levels or tiers of weight management services and these different tiers cover different aspects.
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This is the structure of the weight management services in UK.
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Tier 1, it includes preventive services, which are dietary advice, physical activity, and behavioral changes.
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Tier 2 services include lifestyle, multi -component weight management, and both
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Tier 1 and Tier 2 services are provided by local authorities.
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Tier 3 service is the specialist multidisciplinary weight management service, and Tier 4 service is more or less similar to Tier 3,
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but in addition, patients can undergo bariatric surgery if they are eligible.
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Both Tier 3 and Tier 4 services are provided by local commissioning groups.
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So as healthcare providers and some of the patients who are listening to this,
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and especially the commissioners who are providing funding for the weight management services, it is important we understand why we have to invest in weight management.
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Studies have shown
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that a moderate weight loss of 5 -10 % of body weight is associated with reduction in blood pressure and cholesterol,
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improved control of blood sugar and reduced incidence of type 2 diabetes, reduction in chronic conditions such as osteoarthritis of the knee,
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hepatic steatosis and non -alcoholic fatty liver disease.
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Weight loss can lead to improvement in quality of life,
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depression, mobility, sexual dysfunction and urinary stress incontinence and it can improve the symptoms of polycystic ovary syndrome and infertility in women.
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There's also reduction in the incidence of cancers and overall reduction in healthcare costs and mortality.
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And studies have also shown that interventions with best evidence of success include the following elements.
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They address both eating and physical activity.
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They provide well -established behavior change techniques such as specific goal setting, relapse prevention and self -monitoring.
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They encourage the development of social support in the plan changes and include a strong focus on maintenance.
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Coming to tier 3 weight management service, it is a clinician -led multidisciplinary team,
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potentially including a physician, specialist nurse, specialist dietitian, psychologist, psychiatrist and a physiotherapist.
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They provide non -surgical intensive weight management with medical therapy with an MDT approach.
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This is the structure of the tier three weight management service at North Cumbria Integrated Care NHS Foundation Trust.
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Our core clinical group is formed by a bariatric physician,
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dietician, physiotherapist, CBT therapist and a psychologist.
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We provide eight weeks of weekly group education
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and one -to -one consultations to the needy patients
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and we signpost the patients for further support if needed and we provide onward specialist referrals as well.
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Once the patients complete the tier 3 weight management service
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they will be eligible to be referred to tier 4 weight management service if they're eligible.
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In parallel to this co -clinical pathway we have our medical pathway where we prescribe weight loss medications
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and it runs from 12 months to 24 months.
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These are our entry criteria for the tier 3 weight management service which I will not go into detail.
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At NCIC we provide eight weeks of group sessions.
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We initially provide an introductory session where the patients go through everything
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that we provide as a brief introduction and thereafter they can opt into the service to undergo the eight -week course.
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We follow the NICE guidelines.
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We offer practical and safe advice about physical activity and healthy eating.
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We use evidence -based behavioral change techniques, provide ongoing motivation, motivational support and follow -up.
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We aim a target weight loss of 5 to 10 %
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of body weight at a realistic pace of 0 .5 to 1 kilogram per week.
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And it's just beyond 3 years since our inception.
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These are some of our data.
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3 ,745 patients have been referred to us
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and we have accepted 3 ,274 patients our average patient has a weight of 129 .7 kilograms
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and a BMI of 46 .2
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so they are severely obese these are our referral trend
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you can see over time the number of referrals has gradually increased
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this is the distribution of our referral according to the age group
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Again, you can see majority of our referrals are to young to late adults.
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This is the distribution of referrals according to the geographical area, and majority of our referrals are from Carlisle.
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This is the distribution of referrals according to the deprivation index, and you can see majority of our referrals are coming from highly deprived areas.
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We have 2 ,836 females in our service and 16 patients with learning difficulties.
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These are some of our outcome data.
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What I would like to bring your attention to is the average weight loss.
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Average weight loss post group is 2 .45%.
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At six months, it is 5 .56%.
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6%.
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And at 12 months, it's 6 .5%, indicating that we have met our targets.
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And we have referred 83 patients to tier 4 weight management service, and most of them have already undergone bariatric surgery.
389
These are some of our data from the medical pathway.
390
We have started 50 patients on liraglutide, which is succenda.
391
At three months, our patients had 10 .3 % weight loss.
392
At six months, 15 .7 % weight loss.
393
At 12 months, 16 .3 % weight loss.
394
I don't have any data from our VGOVI patients because we recently started it.
395
And we have plans to start test hepatite in the near future.
396
In this graph, you can see in addition to the weight loss, our patients had improved HbA1c depicted from the red line
397
and liver enzymes depicted from the orange line and the cholesterol depicted from the gray line.
398
These are our patient feedback data as shown in the green area
399
you can see majority of our referral have been majority of our feedback have been really good.
400
I would like to finish my presentation with the story of
401
Mr. Alan Smith who is a 69 year old gentleman from Cockermouth.
402
He was diagnosed with prediabetes, hypertension, osteoarthritis, atrial fibrillation when he was referred to us.
403
He lost 28 .6 kilograms which account 20 .4 percent at 12 months.
404
His HbA1c normalized.
405
He came off most of the antihypertensive medications.
406
He would like to say a few words as well.
407
Hello, my name is Alan.
408
I was diagnosed as a borderline diabetic, so I was referred to a diabetic consultant.
409
I went through the benefits of weight loss to help
410
and alleviate years my condition i suggested tier 3 weight management and a 12 -week course to lose weight
411
i was skeptical at first as i've tried every day for
412
the past 50 years always yo -yoing back back again
413
so i joined the tier 3 weight management journey back in september 2022 right from the word go i knew
414
that this was different the organizational backup the consultant physio dietitian and the psychologist kept you on track
415
the support was something I had not experienced doing other weight loss weight loss journeys
416
it took a few weeks to get into the mindfulness
417
part of the course but the team helped cajoled and with an expert to move you along at a pace
418
I'd run it out of a saxophone daily injections after 5 weeks
419
these were a godsend helped me to come to terms with my eating habits.
420
Expressing my need to eat, I went down from 3 ,500 calories a day to 1 ,500.
421
After 12 weeks, I reached a good one. Would I manage?
422
Would I cope?
423
The answer was yes.
424
The weight dropped off me.
425
Initially, I have lost five and a half stones.
426
The words of psychologists still kick in, along with a dietician whose examples of when and what to eat.
427
The change in my lifestyle has been dramatic.
428
The diet base has gone.
429
I am fitter, more active and ideally achieved 10 ,000 steps.
430
I'd like to buy a new wardrobe to give me more chance than what I'd buy.
431
I had nothing but praise for the Tier 2 -3.
432
And thoroughly and wholeheartedly recommend
433
Tier 3 suits to anyone.
434
But at the end of the year, if you don't change, nothing changes.
435
It's in your own hands.
436
The programme will work if you want it to.
437
Thanks again Tier 3.
438
Thank you very much.
439
Bye.
440
This is the Tier 3 wage management service team at NCIC.
441
Thank you.
442
Thank you, Dr. Ranatunga.
443
That was excellent.
444
Come to the end of the webinar.
445
Can I thank most sincerely, Trisha Tan and Nishaya Ratatunga for their excellent presentations.
446
Thank you.
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Pronuncia con IAVoto per ogni frase
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Vocabolario e note di pronuncia per questa lezione
Questa lezione di conversazione si basa sul video “CumbriaMed Research Webinar Series: Obesity”. Le parole che ritornano più spesso: weight, loss, obesity, drug, disease. Questo video contiene 445 frasi e 5460 parole da ripetere con lo shadowing. Il parlato dura 46:14. Chi parla mantiene un ritmo costante di circa 118 parole al minuto, comodo per lo shadowing. Solo il 79% delle parole rientra nelle 3.000 più comuni dell’inglese, quindi il lessico è impegnativo.
Vocaboli chiave di questo video
15 parole del video che vale la pena imparare, con pronuncia e significato:
| Parola | Pronuncia | Significato |
|---|---|---|
| obesity sostantivo | /ə(ʊ)ˈbiːsɪti/ | obesità |
| diabetes sostantivo | /ˌdaɪəˈbiːtiːz/ | diabete |
| tier sostantivo | /ˈtɪɚ/ | strato, ripiano |
| reduction sostantivo | /ɹɪˈdʌk.ʃən/ | sgravio, taglio |
| hormone sostantivo | /ˈhoɹmoʊn/ | ormone |
| essentially avverbio | /ɪˈsɛnʃəli/ | in essenza |
| kidney sostantivo | /ˈkɪdni/ | rene |
| chronic aggettivo | /ˈkɹɑ.nɪk/ | cronico |
| graph sostantivo | /ɡɹæf/ | grafico |
| cardiovascular aggettivo | /ˌkɑːdi.əʊˈvæskjʊlə(ɹ)/ | cardiovascolare |
| versus | /ˈvɝsəs/ | contro |
| dose sostantivo | /ˈdəʊ̯s/ | dose |
| lifestyle sostantivo | /ˈlaɪfˌstaɪl/ | stile di vita |
| imperial aggettivo | /ɪmˈpɪɹ.i.əl/ | imperiale |
| overweight aggettivo | /ˌoʊvɚˈweɪt/ | in sovrappeso, sovrappeso |
I phrasal verb che sentirai
| Parola | Significato |
|---|---|
| go through verbo | attraversare |
| drop off verbo | addormentarsi, appisolarsi |
| put together verbo | assemblare, montare |
La grammatica di questo video
Le strutture che chi parla usa di più, con le parole esatte del video:
| Struttura | Nel video |
|---|---|
| Present perfect continuous have/has been + -ing — un’azione iniziata prima e ancora in corso | We've been using · we've been working |
| Present perfect have/has + participio passato — un’azione passata che conta ancora adesso | has heard · we've listed · have only had |
| Forma passiva be + participio passato — conta ciò che accade, non chi lo fa | are associated · is secreted · is known |
| Frasi relative who / which + frase — un’informazione in più su una persona o una cosa | glucagon, which is · version, which is · Semaglutide, which is |
Pronuncia a cui fare attenzione
Chi parla usa 41 contrazioni e forme ridotte, come we've, I'm, I'd. Pronunciale nella forma breve, così come le senti.
- I suoni “sh” e “zh”: reduction /ɹɪˈdʌk.ʃən/, essentially /ɪˈsɛnʃəli/, medication /mɛdɪˈkeɪʃən/, specialist /ˈspɛʃəlɪst/, tissue /ˈtɪʃ.(j)u/
- Parole lunghe — attenzione all’accento: obesity /ə(ʊ)ˈbiːsɪti/, essentially /ɪˈsɛnʃəli/, cardiovascular /ˌkɑːdi.əʊˈvæskjʊlə(ɹ)/, imperial /ɪmˈpɪɹ.i.əl/, medication /mɛdɪˈkeɪʃən/
I suoni difficili per chi parla italiano:
- /h/ — va soffiata, non è muta: hormone /ˈhoɹmoʊn/, behavioral /bɪˈheɪvjəɹəl/, horizon /həˈɹaɪ.zən/, habit /ˈhæb.ɪt/, highlight /ˈhaɪˌlaɪt/
- Consonante finale — senza aggiungere una vocale dopo: diabetes /ˌdaɪəˈbiːtiːz/, chronic /ˈkɹɑ.nɪk/, graph /ɡɹæf/, versus /ˈvɝsəs/, dose /ˈdəʊ̯s/
- /æ/ — più aperta della “e”: graph /ɡɹæf/, cardiovascular /ˌkɑːdi.əʊˈvæskjʊlə(ɹ)/, appetite /ˈæp.əˌtaɪt/, gradually /ˈɡɹæd͡ʒuəli/, pathway /ˈpæθˌweɪ/
Come esercitarsi con questo video
- Ascolta tutto il video una volta senza parlare e annota le parole che non conosci.
- Fai shadowing frase per frase a velocità normale, ripetendo ognuna finché il tuo ritmo coincide con quello di chi parla.
- Registrati e confronta con l’originale, facendo attenzione a parole come obesity, diabetes, tier.
Cos'è la tecnica dello Shadowing?
Shadowing è una tecnica di apprendimento delle lingue supportata da studi scientifici, originariamente sviluppata per la formazione dei traduttori professionisti e resa popolare dal poliglotta Dr. Alexander Arguelles. Il metodo è semplice ma potente: ascolti un audio in inglese di madrelingua e lo ripeti immediatamente ad alta voce — come un'ombra che segue il parlante con un ritardo di solo 1–2 secondi. A differenza dell'ascolto passivo o degli esercizi di grammatica, lo shadowing costringe il tuo cervello e i muscoli della bocca a elaborare e riprodurre simultaneamente i modelli di discorso reale. La ricerca dimostra che migliora significativamente la precisione della pronuncia, l'intonazione, il ritmo, il discorso connesso, la comprensione dell'ascolto e la fluidità del parlato — rendendolo uno dei metodi più efficaci per la preparazione alla prova di speaking dell'IELTS e per la comunicazione reale in inglese.