Care is Primary: Practical Tips for Everyday Practice

Welcome to Care is Primary, a podcast dedicated to providing primary care clinicians with summarized latest insights, clinical updates, and expert discussions to enhance patient care. Join us as we explore essential topics and share practical knowledge for your everyday practice. Here are your hosts, doctors James Kim and Akshay Jain.

Welcome. I'm doctor Akshay Jain with doctor James Kim live on -site at the American Diabetes Association twenty twenty four Annual Conference in Florida. Now Doctor Kim and I have been very successful in dodging all the gators in Florida, just so that we can come and share the top pearls for primary care that we have learned in just two days of this conference so far. Doctor Kim, how's the conference been for you?

Yeah it's been, well first of all Orlando has been really hot, so it's been a bit of a problem for someone from Calgary so, but otherwise the conference itself has been absolutely fantastic, and today's what day three now, is that right? Yeah and we do have one more day but there have been so many interesting data that came out, I think it's worth to discuss some of these key points.

All right so for primary care doctors outside in Canada, what are the key things that you have learned that you wanna share with them?

Yeah, so I think sleep, sleep is one of the foundation of our health. You have diet and exercise and sleep. And I think in our practice, even in primary care, we often ignore the impact of sleep but we do know that if you have insomnia, then your risk of metabolic profile goes up really badly. Your BMI goes up, your A1C goes up, cholesterol goes up and so on just because you don't sleep. And one of the sessions that they talked about here is actually the impact of obstructive sleep apnea and some of the key findings from this one particular trial using this medication called tirzepatide.

So this study is called Surmont OSA. We do know that by treating OSA with whatever devices or means interventions it may be, it improves things like blood pressure, insulin sensitivity and they confirm those things as well. So Doctor. Jain, actually do you wanna talk more about what you thought about the Sumant OSA study?

For sure. So I think let's just break it down into small bites here. But if I understand correctly, what you're saying here is sleep matters a lot and both quality as well as quantity of sleep are very So what we learned is that if someone has less than six hours of sleep from a metabolic perspective, it is not healthy. It leads to very bad consequences, hypertension, dysglycemia, all the other bad stuff that happens, and the quality of sleep matter. So that's where obstructive sleep apnea comes into play.

Now tirzepatide that you mentioned Doctor Kim, that is an incretin medication. So it's in the class of medications called GLP-one receptor agonist combined with GIP. In Canada, the brand name under which it's currently available is called Mounjaro. And in this study, what they did was they looked at tirzepatide in individuals that are living with obesity and who have obstructive sleep apnea. They had two groups of patients, one who had obstructive sleep apnea and were not using a CPAP machine and the other who have obstructive sleep apnea and who were using a CPAP machine.

And on an average, these individuals had an AHI, which is an apnea hypopnea index. By the way, Doctor Kim, what exactly does it mean? I don't know much about this.

Yes, so that's when people basically stop breathing in the middle of the night and the numbers come to per hour. So if you have an AHI of let's say 10, then you basically stop breathing about 10 times per hour at night. So anything from one to 15 is considered to be mild and in this particular study, I mean they were looking at people who were having basically AHI of 51. So that means they were stopped breathing 50 times per hour. Now the crazy thing is that the patient doesn't know that they're stopped breathing, it's usually the spouses or partners that actually noticed this.

But 51 is a severe sleep apnea and we are obviously very concerned about these patients. And it's not just those, mean, oxygen saturation level actually went down pretty significantly whenever they had this apnea episode.

Wow. Now I don't know about you, but if my partner is snoring and having apnea episodes 50 times an hour, well, for one, my sleep would be disturbed, but more importantly, my is not gonna be a happy camper in the daytime, they'll be tired all the time.

So

these guys had a lot of AHI elevated there. And what they saw in the study was this medication has been approved for the management of diabetes in Canada, but in many other countries in the world, in The US for instance, it's also approved for the management of obesity, including in people who do not have diabetes. And what this saw was that in these individuals, when they started using tirzepatide, they had a weight loss of 18 to 20% on an average but at that same time their apnea hypopnea index, their AHI, dropped by 50%. That's phenomenal. So a drop of fifty percent in nearly half of these individuals on the medication.

So I mean I'm no expert but I think that sounds really good.

That is a crazy number. Mean I'm not a sleep doc, sleep physician but I don't think anything, any devices has come anything close to that. And what's also really fascinating in this same study was, they were looking at the people where their AHI went so low that they almost called it sleep apnea remission to a point that maybe they may not require a CPAP machine. So imagine you're one of those person who carries a CPAP machine around all the time and it's quite annoying especially when they're traveling and stigmatizing in some sense and you can come off that machine, the quality of life in some patients can actually improve as well. So it's absolutely mind blowing data and their symptoms improved.

So they had a certain measurement to see if their daytime function actually improved as well and it was absolutely phenomenal. I haven't seen anything like that. It's incredible.

Now that's really important because I mean I don't know how many of us have actually seen those masks. They are very uncomfortable. A patient of mine, his wife said that he looked like the villain from Batman Begins when he wears his CPAP machine. So clearly, that thing can make a big impression. But most important, according to me in the study, what I saw that was most impressive was not only of course this dramatic drop in their AHI, but we also saw that there was a blood pressure reduction by 10 millimetres systolic just by virtue of using this medication.

So again, quality of sleep improving, quantity of sleep potentially improving, and an improvement in all these metabolic parameters, that's a win.

Well, that's a massive win. Mean, you're talking about 10 points drop. I mean, that's as good as some of the medications. Actually, it's probably better than some

of the

antihypertensive medication that we gave. That's All right.

Sleep apnea being discussed at a diabetes conference, that's new. Else did you think that was new at this conference?

Yeah. So inhaled insulin. Oh my gosh. There is actually insulin that you can now inhale. That's that's pretty interesting.

So what did you think of the inhaled insulin and the talker?

It was a breath of relief. Well, okay, no pun intended there, but what we are also seeing is for the longest time we've had patients who are just so needle shy that they feel that they just don't wanna start taking any insulin injections because that needle phobia, there's actually a term for that by the way Doctor Kim, did you know the fear of needles is called trypanophobia?

That sounds like something else but anyway.

So for a lot of patients, they don't want to start insulin because it's only been available in an injectable form up until now when we have inhaled insulin. So let me give you a little bit of a breakdown, how was it developed and what does it do? So inhaled insulin is currently not available in Canada and this is taught to be a replacement for short acting insulin. For those of your patients who are on bolus insulin, they're taking prandial insulin before their meals, that's what they are using inhaled insulin for. Now inhaled insulin that is developed is very similar to regular insulin or what many of us know as Humulin R or Novalin R, so that's the regular insulin.

Except they've managed to tweak this quite a bit and in this inhaled version, this insulin has actually developed quite a few very interesting characteristics. So number one, its pharmacokinetic and pharmacodynamic profile is hugely different there, so what tends to happen is this insulin starts working very very rapidly. So it'll start working very quickly and it's out of the body very quickly, so in fact its total effect would last only for about an hour or an hour and a half or so. So it'll have a nice big peak and then it's out of the body, which means that it can be dosed multiple times and the risk of stacking of insulin, so stacking is when you take too many shots of short acting insulin very close together and then all these insulin doses add up and then somebody has a very big low sugar. So the risk of stacking is not as much because it's in and out of the body very quickly.

One cool thing that they saw in this study was that because it's in and out so quickly, it can be even given at bedtime without worrying about a middle of the night hypoglycemia. So I think that's important.

That's very important. I mean, nocturnal hypoglycemia in patients or anyone who has diabetes or any medication that can cause hypoglycemia is a massive concern. This is really interesting. However, I am just wondering from a family doctor's perspective, what about people with asthma and the people with COPD where their lung function may not be very good, especially in some of these really bad COPD patients, they can struggle to take a deep breath in and can they actually inhale this properly to actually have some effect. I wonder if that was discussed.

That's a good point. Hold your breath. I'll get

to the answer. So the answer to that is that we should not be using it in individuals who have asthma and COPD. More importantly, it's very important to get baseline pulmonary function testing. Now this can be something as simple as a spirometry testing, that should be done at baseline, and then six months after initiation on inhaled insulin. And then after that annually, and this is even if people have no pulmonary symptoms, these need to be monitored on a regular basis.

If you notice that the FEV1 drops by 20% or more from baseline, that's when we got to stop the inhaled insulin.

That's a decent drop but I am looking forward to see more data because obviously right now I have more questions than answers at the moment. But regardless it is exciting, the technology is moving and yeah and the next thing I'm guessing patients will ask me is, can we snort insulin too? So hopefully we don't have to answer those questions.

Well, right now patients ask us, don't wanna take something that I have to shoot in my veins. So we pick the drug route of choice.

Yes, totally.

Now we've got a surprise package for our pilot episode. We have a very special guest joining us, someone that needs no introduction, Doctor Alice Cheng, endocrinologist from Toronto, who is actually the co chair of the American Diabetes Association Conference this year. Welcome Doctor Cheng.

Thank you very much for having me.

So one thing that really caught my eye was the fact that they showed some data regarding fenofibrate in individuals with retinopathy. Doctor Chang, what were your impressions regarding this study?

So the LENS trial was presented for the first time in the world here at the ADA and simultaneously published. And and I think what's very cool about it is that it's it's taking an old drug, fenofibrate, hundred and forty five milligrams a day that we've had forever, and repurposing it, I guess, and and showing its value in a completely different space. I mean, it was born in the lipid space. Traditionally, it's been used for lowering triglycerides. But here, it was actually studied to see if it could reduce the progression of diabetic retinopathy as well as maculopathy.

So meaning regular diabetic retinopathy that we all think about, but also, macular edema. And they were able to, in fact, show that fenofibrate, an old drug, has was very effective in terms of reducing progression of diabetic retinopathy and maculopathy. So I think something that all of us can remember and use because all of us will see people that have diabetic retinopathy. And to be honest, I'm not sure that our ophthalmology colleagues will be as comfortable initiating an oral systemic therapy, Whereas us, all of us part of this, all of us, certainly all of you who are listening are definitely in the position to make that difference.

What was very interesting in my opinion was that these individuals didn't even have high triglycerides. Right? So this is irrespective of the triglyceride that the phenofibrates were still working. James, do you use a lot of phenofibrates in your practice and if so for what patients?

Yeah, so I work in the immigrant population area, so a lot of Asian populations and they tend to have a lot of elevated triglyceride and some of them do have a pretty high triglyceride as well. So those are the main people that I would use the medication to lower the hypertriglyceride. So that's a

really important point. Doctor Cheng, at what triglyceride level if you're using fibrates for triglyceride, at what level should we be using, fenofibrates?

So if we're using it for triglyceride purposes, then it's typically greater than 10. Because greater than ten millimoles per liter is when we need to be concerned about potential for pancreatitis. But we know that using it for levels that are lower than that has not been demonstrated to reduce cardiovascular outcomes. But that's if we're using it for that purpose. And I think now we need to start getting used to seeing this prescription or this medication being offered to someone whose trigs are not even up, and they're just someone who has eye disease from their diabetes.

It's quite the eye opener. So if you think about it, we now have two disease conditions overlapping with eye disease and other metabolic aspects where we're using medications. So let me let me tell you what I'm thinking of. So we have fenofibrates that do not have any cardiovascular protection, but they do have eye protection from retinopathy. And then we have fish oil supplements.

So we know that ophthalmologists use it quite often, but they don't have any cardiovascular benefits. So that's the other reason why someone might be taking these medications from an ophthalmology perspective. And they probably don't have much cardiovascular benefit, which is the first reason why we initially developed these medications. One quick question for you. So gemfibrozil does have increased interaction with people who are on statins, increased risk of rhabdomyolysis and myalgias.

Is the risk similar or lower with fenofibrates?

So it appears to be lower with fenofibrate. The the main concern is with gemfibrozil, which frankly is not being used a whole lot anymore. Whereas fenofibrate, I guess, took over, if you will, from gemfibrozil for that very reason. And within the context of this clinical trial, there would have been lots of people who are also on a statin because these were people living with diabetes and, obviously, diabetes with a complication already. So for sure, they should have been on a statin.

And there was no reports of any any issues surrounding that. So I'd be very comfortable using fenofibrate in someone who's also using a stent.

Thank you, doctor Cheng. Now we always ask our guests to if they had just one minute to share a key piece of information with our audiences. And maybe let's put it say one minute that if you had to share something very important that you learned at this conference with our primary care audiences in Canada, what would you say?

Well, she thinks about that. Also just want to mention that quite elevated triglyceride level can also cause neuropathy, and that is really, really difficult to treat, with medications. So, even another reason I think we should actually pay more attention to triglyceride. And I do believe that there are some ongoing studies on the impact of triglyceride on cardiovascular disease and actually some cardiologists are saying that we've underestimated the impact of triglyceride on cardiovascular disease, it probably is playing a lot more or bigger role than we appreciate. So it's a very interesting area.

That is the triglycerides do have that persistent cardiovascular risk, although reducing triglycerides may not necessarily help with cardiovascular protection, it's only a marker to suggest that these individuals are at a higher risk and that's where some something like icosapentatile, a medication that has been shown in the REDUCE IT trial to reduce the risk of cardiovascular risk can be very helpful. But we'll probably cover that in more detail in the future at some other episodes. So Doctor Cheng, key clinical pearl that you want to share with our audience.

So one of the panel discussions that that I thought was fantastic at this session was a panel consisting of endocrinologist as well as a gastroenterologist as well as anesthetist to discuss the question of incretin therapies, GLP one plus or minus GIP receptor agonist in the perioperative setting, which has become an extremely hot topic with patients having procedures canceled, stuff they've been waiting for for nine months being canceled last minute because the anesthetist was concerned about the potential for food still being in their stomach and therefore aspiration when they had an anesthesia. What I loved about the panel was that they came together and actually came up with a consensus recommendations. Now these are not formal associations, but just three clinicians who care coming together to make make, some recommendations, which were fantastic. And and a couple of big ones that I'll I'll just say here that I think are relevant is that we should avoid elective surgeries during the titration phase of someone starting a GLP one plus or minus GIP receptor agonist. And then the other one is perhaps altering the dietary habits leading up to the surgery.

So most patients will be NPO after midnight prior, but one could consider implementing fluid diet or having a couple of days of, fluids without solids prior to the surgery. And I I said two, but I meant three. And the third one that's important is that if someone is having symptoms, GI symptoms, then that person might be at higher risk and therefore someone that we might wanna implement maybe liquid diet leading up to the surgery itself.

Fantastic. That is the awesome trial. Thank you so much, doctor Chang, and we look forward to having you back at a future episode as our guest.

Fantastic. Thank you.

So doctor Jane, you're a huge fan of the SELECT trial and the data. So what do you think of the SELECT trials?

In one word, landmark. It is a game changer trial. Have, as you mentioned, we've never seen a study this big, right? We had seventeen thousand people living with obesity, who have, you know, that we are looking at cardiovascular risk perspective and what the occurrence of MACE events was. So MACE is major adverse cardiovascular events, which includes heart attack, strokes and cardiovascular death.

And we saw a stupendous drop in the occurrence of these MACE events in people living with obesity who are giving the semaglutide two point four milligram per week. Now what I especially want to point out is that every single person in this study did not have diabetes. However, there was a big group of individuals there who had pre diabetes and what we saw at the American Diabetes Association conference was they looked at these individuals with pre diabetes who were started on semaglutide two point four milligrams, and they saw how many of these individuals actually go on to develop diabetes. So it's very interesting. Doctor Kim, if you have a patient in your practice with pre diabetes, and if they ask you a question that, hey, I'm gonna start exercising, control my diet, What do you think?

How many of those individuals would go ahead and develop diabetes in the next five years say? Oh my gosh.

I don't know, maybe twenty percent, thirty percent.

So if even with the best diet and exercise, it's roughly about forty to fifty percent of these individuals will still end up developing diabetes. Guess how many of these individuals in this trial who were on semaglutide two point four milligrams actually went on to develop diabetes in the four years that the study went on for?

Wow, with this impact probably like fifty sixty percent. Oh, sorry. No, they probably didn't go into diabetes. Maybe ten percent.

Oh, so close. It's twenty three percent of people actually went on to develop diabetes over four years, which is much better than what you have seen with any medication. So we have previous studies that have been done with metformin, with acarbose, all these medications showed that the overall risk of developing diabetes is still quite high, but only twenty three percent of these individuals are now going on to develop diabetes in this trial. So I think that is also very important because when we tell these individuals who obviously because of obesity they are at a higher risk of developing diabetes, If we can help prevent progression to diabetes, that's also a very big win. Oh, that's

a massive win. Yeah, agree. There was also presentations on the one of the very fashionable diet intermittent fasting, talking about whether you can actually prevent people going from pre diabetes to diabetes. And we are just waiting for some bigger trials but the data's are quite interesting. It definitely reduced the HOMA IR which is reflective of insulin resistance that went down, the whole metabolic profile actually went down as well.

So A1c went down, the fasting glucose went down and so on. So a really, really fascinating world right now. So maybe we can achieve a lot of people into the remission stage, not necessarily remission because by definition, you're in remission, you shouldn't be on any medication but, to put them into the normal sugar level, I think that's a massive win And think of all the complications you can prevent, it means unreal. Unreal world, yeah.

Totally. Any other highlights that you wanna talk about before we sign out today?

Yes, so there was a very interesting session on the impact of incretin, so the GLP-one receptor agonist in asthma. Now the moderator started by, or the chair of the session actually started by saying that, well, lung has never been part of diabetes conference before. And this is the first time that we are actually talking about lung conditions in diabetes conference, which is really interesting. And there's no lung or asthma COPD related guidelines in American Diabetes Association guidelines and not in Canadian guidelines as well. What was very interesting during the session was that if you have diabetes and worsening of diabetes, that actually worsens your asthma and COPD control, especially if they're obese patients.

There are some current studies going on with GLP-one receptor agonist and with metformin as well to see if you can actually reduce the inflammation and improve the control of our asthmatic patients. Because you have to understand that these obese asthmatic patients are so steroid resistant, it is difficult to treat them and get them under control because the most important treatment of asthmatic patients as you know is a steroid, corticosteroid. But they are so resistant to these medications therefore we land up using some of the off label medications and many of them actually land up being on biologics. Therefore if we can have another therapy, weapon in our armory and prevent them from using another steroid, another rounds of steroid, that's a huge win therefore this is a really, really interesting field and I'm sure in five to ten years time, we'll be talking a lot more about diabetes and lung conditions. So in the past, as you know, we focus a lot in diabetes and kidney disease and diabetes and heart disease and liver disease and all for good reasons.

And now the liver thing is exploding right now. And I think in about five, ten years, we'll be talking a lot about diabetes and lung. And they even coined an interesting term, they coined the term fatty lung disease. So it was just, I didn't think the speaker was very serious but it was quite interesting terminology. So yeah, so that was my highlight.

So these are people of South Asian heritage and we all have seen in our practices that, you know, there will be certain groups either based on phenotype, which is basically their body characteristics or their genotype, their genetic characteristics that increase their potential for developing diabetes. So case being in point, if somebody has obesity, that's a phenotypic risk of developing diabetes. And if somebody has both parents with type two diabetes then that's a genotypic or genetic risk of developing diabetes. Now in this lecture that was given by Doctor Veen Mohan from India, they showed data from over a 20,000 Indians all over India where they did some very elegant phenotypic and genotypic assessments. What they've discovered, and this is all very strong science that they showed us, is that when South Asians are born right at the time of birth, South Asian babies tend to have lesser amount of insulin and more leptin which does significantly increase their tendency to develop insulin resistance.

This phenomenon continues over through their childhood into adulthood And that's where it see we have seen that insulin resistance does increase also when we tend to gain weight. Where we store it becomes very important. So we've seen that for majority of individuals that are of white origin, they would be having increased deposition of fat in the subcutaneous region, whereas for South Asians it's deposited in the abdominal region, so it's in the viscera into the organ, so it's visceral adiposity. Also what was seen was that, remember I said how at birth they have a less amount of insulin production capacity? Well as we grow older, our pancreas is growing older and there can be exhaustion of beta cells, so a lot of times in what was seen in their studies is South Asians when they develop dysglycemia, impaired fasting glucose occurs first and impaired glucose tolerance occurs much later down the line.

So if we focus just on glucose tolerance, then we might be missing out the fasting glucose issue. There's of course a lot of life cell issues related to diet, perhaps sedentary life cells and so on and so forth. But it was very interesting to see how even though all humans are the same at a genotypic level because of ethnicity, some people are at a higher risk of developing diabetes. What the researcher showed is that typically South Asians could develop type two diabetes ten years earlier than other ethnicities and also at a much lower BMI. In fact once the BMI crosses twenty two point zero, South Asians are already at a much higher risk of developing diabetes compared at the same level as a white male who has a BMI of thirty.

So that is very interesting in my opinion. Well that's a take from James and I from sunny Orlando. We really look forward to catching you back at a future episode where we can continue to share with you primary care clinical pearls that we learn and would love to share with you.

Thank you very much for joining us.