Cardiovascular Impact of Diabetes Meds

Listen in as our expert panel discusses which diabetes meds have cardiovascular (CV) benefits.  We’ll review the evidence and discuss the pros and cons of SGLT2 inhibitors (dapagliflozin, empagliflozin, etc) and GLP-1 agonists (dulaglutide, semaglutide, etc) in patients with or at risk for CV disease.

Special Guests:

• Lauren G. Pamulapati, PharmD, BCACP
  • Associate Professor, Ambulatory Care
  • Virginia Commonwealth University School of Pharmacy
  • Clinical Pharmacist, Hayes Willis Health Center/VCU Health
• Christie Schumacher, PharmD, BCPS, BCACP, BCCP, BC-ADM, CDCES, FCCP
  • Professor, Pharmacy Practice
  • Director, PGY2 Ambulatory Care Residency Program
  • Midwestern University College of Pharmacy, Downers Grove Campus
  • Clinical Pharmacist, Northwestern Medicine

TRC Editorial Advisory Board Participant:

• Stephen Carek, MD, CAQSM, DipABLM
  • Clinical Associate Professor of Family Medicine
  • Prisma Health/USC-SOMG Family Medicine Residency Program
  • USC School of Medicine Greenville

For the purposes of disclosure, Dr. Schumacher reports a relevant financial relationship [CGM for diabetes management] with Abbott (speakers bureau).

The other speakers have nothing to disclose. All relevant financial relationships have been mitigated.

This podcast is an excerpt from one of TRC’s monthly live CE webinars, the full webinar originally aired in February 2025.

TRC Healthcare offers CE credit for this podcast. Log in to your Pharmacist’s Letter, Pharmacy Technician’s Letter,or Prescriber Insights account and look for the title of this podcast in the list of available CE courses.

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The clinical resources mentioned during the podcast are part of a subscription to Pharmacist’s Letter, Pharmacy Technician’s Letter, and Prescriber Insights: 

• Chart: Diabetes Medications: Cardiovascular and Kidney Impact
• Chart: Drugs for Type 2 Diabetes 
• Algorithm: Stepwise Treatment of Type 2 Diabetes
• Chart: Comparison of GLP-1 Agonists
• Toolbox: Improving Heart Failure Care

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Chapters

• 0:01 Introduction
• 1:48 CE Information
• 2:31 Cardiovascular Impact of Diabetes Meds

Transcript

This transcript is automatically generated. 

00:00:07 Lauren G. Pamulapati

So I feel like when you're first starting a patient, you think about what is their compelling indication and so are you choosing the GLP agonist or the sglt 2 inhibitor?

00:00:18 Lauren G. Pamulapati

But ultimately, most of these patients are going to require additional pharmacotherapy, not just for their glycemic control, but when you start to think about all of the other benefits that we've already talked about today, right, the cardiovascular health, the kidney health and the liver health, you start to.

00:00:36 Lauren G. Pamulapati

Why wouldn't I add this on?

00:00:43 Narrator

Welcome to medication talk, the official podcast of TRC Healthcare, Houma pharmacist letter prescriber insights and the most trusted clinical resources. Proud to be celebrating 40 years of unbiased evidence and recommendations.

00:00:57 Narrator

On today's episode, listen in as our expert panel discusses which diabetes meds have cardiovascular benefits.

00:01:04 Narrator

We'll review the evidence and discuss the pros and cons of sglt 2 inhibitors and GLP 1 agonists in patients with or at risk for CV disease.

00:01:13 Narrator

Our guest today are Doctor Lauren G Pamela Patti from the Virginia Commonwealth University School of Pharmacy, and Doctor Christy Schumacher from the Midwestern University College of Pharmacy.

00:01:25 Narrator

You'll also hear practical advice from TR CS Editorial Advisory Board member Doctor Steven Carrick from the USC School of Medicine Greenville.

00:01:34 Narrator

This podcast is an excerpt from 1 of Trc's monthly live CE webinars. Each month, experts in frontline providers discuss and debate challenges in practice.

00:01:42 Narrator

Evidence based practice recommendations and other topics relevant to our subscribers.

00:01:48 Narrator

And now the CE information.

00:01:52 Narrator

This podcast offers continuing education credit for pharmacists, pharmacy technicians, physicians and nurses.

00:01:59 Narrator

Please log into your pharmacist letter pharmacy technicians letter or prescriber insights account and look for the title of this podcast in the list of available CE courses.

00:02:09 Narrator

For the purposes of disclosure, Dr. Schumacher reports a relevant financial relationship as a speaker's Bureau participant with Abbott.

00:02:17 Narrator

The other speakers you'll hear have nothing to disclose.

00:02:20 Narrator

All relevant financial relationships have been mitigated.

00:02:25 Narrator

Now let's join TRC editor, Doctor Sarah Clockers and start our discussion.

00:02:32 Sara Klockars

So to get us started, Christy, could you give us a high level overview of which diabetes meds can reduce cardiovascular risk?

00:02:41 Christie Schumacher

Yeah. So when we look at the different blood glucose lowering medications, there's really 2 main types of drugs right now that have shown benefit reducing cardiovascular risk and their respective cardiovascular outcomes trials.

00:02:53 Christie Schumacher

So if we look at the different cardiovascular outcomes trials, they were designed by looking at historically the three-point Mace which included non fatal mi non fatal.

00:03:01 Christie Schumacher

And then cardiovascular.

00:03:04 Christie Schumacher

So the ones that showed gluco slurring reduction as well as decreasing cardiovascular death were actually lurglitide from the leader trial semaglutide from the sustained 6 trial and in deeleglotide for the rewind trial. So those are really the three GLP one receptor agonists that have demonstrated cardiovascular benefit.

00:03:23 Christie Schumacher

Ezentitide once weekly, was neutral in its cardiovascular outcomes trial and an oral semiglotide trial.

00:03:29 Christie Schumacher

So actually we just got the high level results for it from the sole trial which showed that oral STEM did have cardiovascular benefit, but that hasn't been published yet.

00:03:38 Christie Schumacher

Only have the high level data so.

00:03:40 Christie Schumacher

We know that potentially maybe oral semaglutide might have benefit as well. Based on those results.

00:03:47 Christie Schumacher

And then for the sglt 2 inhibitors, they've also shown cardiovascular benefit and those ones that have shown benefit in their cardiovascular outcomes trial where ConAgra flows into the cannabis program and impagl flows in and the infrared trial.

00:04:00 Christie Schumacher

As far as.

00:04:02 Christie Schumacher

I know that's the new one. We know it is.

00:04:04 Christie Schumacher

Is the brand.

00:04:05 Christie Schumacher

We're still waiting on the cardiovascular trial for that.

00:04:08 Christie Schumacher

So the surpassed cardiovascular outcomes trial is going to look at tirzepatide and compare it to delaylatide for its cardiovascular outcomes trial.

00:04:15 Christie Schumacher

That one's ongoing.

00:04:16 Christie Schumacher

So right now, we still don't know really if TIRZEPATIDE reduces cardiovascular risk.

00:04:22 Sara Klockars

Great. Thank you.

00:04:24 Sara Klockars

We'll shift to you which diabetes meds possibly have cardiovascular.

00:04:29 Sara Klockars

We always get a lot of questions about metformin and pioglitazone, and I'm hoping you can.

00:04:35 Sara Klockars

Enlighten us on their role and and their effects on mice.

00:04:41 Lauren G. Pamulapati

Absolutely thank.

00:04:42 Lauren G. Pamulapati

So Metformin obviously has been one of our backbone of therapies for so long and I think a lot of that obviously comes from the UKPDS child that showed the reduction in mortality and morbidity in patients who were prescribed metformin.

00:04:57 Lauren G. Pamulapati

And so I think that's where we're seeing some of the that possible benefit that you see with Mace. And then for pioglitazone really it's being driven by stroke reduction and primarily in recurrent stroke. So in patients who have had a history of stroke or Tia, that's what we.

00:05:14 Lauren G. Pamulapati

Seeing.

00:05:15 Lauren G. Pamulapati

That benefit that we see in the iris and proactive trials, but really we're seeing piaglitazone further down your algorithm when you're thinking about treating your patients with diabetes after you're using an sglt 2.

00:05:27 Lauren G. Pamulapati

Hivara GLP and really trying to prevent recurrent stroke in those patients.

00:05:34 Sara Klockars

Great. Thank you.

00:05:35 Sara Klockars

And then do we have any medications for diabetes that increase cardiovascular risk?

00:05:43 Lauren G. Pamulapati

So thinking about gluten specifically in tzds, that increased risk of fluid retention and heart.

00:05:50 Lauren G. Pamulapati

And so we really want to be avoiding any tcds pioglitazone being the one that we see often being used nowadays.

00:05:59 Lauren G. Pamulapati

That's the.

00:06:00 Lauren G. Pamulapati

We'd really want to be avoiding and patients who have a history of heart failure.

00:06:04 Sara Klockars

Great. Thank you.

00:06:06 Sara Klockars

So, Lauren, how do GLP 1 agonists and sglt 2 inhibitors reduce cardiovascular risk?

00:06:14 Sara Klockars

What's the mechanism behind this benefit, and do they impact inflammation or or what are their effects?

00:06:21 Sara Klockars

Based on what we.

00:06:22 Sara Klockars

Today.

00:06:23 Lauren G. Pamulapati

Right, I.

00:06:24 Lauren G. Pamulapati

Isn't this like the question that I feel like everyone was always trying to dive into when they started coming out? We saw these great benefits.

00:06:31 Lauren G. Pamulapati

So Geo Paganists and the sglt 2 inhibitors are reducing your cardiovascular risk by improving that metabolic control, lowering some blood pressure.

00:06:39 Lauren G. Pamulapati

Really reducing inflammation and improving endothelial function and in some cases really stabilizing those arthroscotic plaques.

00:06:47 Lauren G. Pamulapati

So we think about our GL PS really acting through the anti-inflammatory pathways.

00:06:52 Lauren G. Pamulapati

Or sglt 2 inhibitors are really impacting our hemodynamics via that urine sodium excretion and reducing that oxidative stress and so.

00:07:02 Lauren G. Pamulapati

I think that really helps when you're thinking about when we'll talk about as we continue, like what medications are we reaching for.

00:07:10 Lauren G. Pamulapati

Are we reaching for our GL PS with the acbd risk and our Sglt 2's first for heart failure risk and thinking mechanistically that really is helping you kind of make sense when you think back to how they're impacting your card?

00:07:23 Lauren G. Pamulapati

Disease.

00:07:25 Sara Klockars

Thank you.

00:07:26 Sara Klockars

And then Christy, can you comment on benefits of GLP one agonists on Mace?

00:07:36 Christie Schumacher

Yeah. So when we look at the original cardiovascular outcomes trials, most of the patients in the trial were over the age of 80 and they had a history of cardiovascular disease, chronic kidney disease and heart failure or they were a little older over the age of 60 with.

00:07:49 Christie Schumacher

Or more risk factors for cardiovascular disease.

00:07:52

So.

00:07:52 Christie Schumacher

When we think about the GOP one receptor agonist and looking at.

00:07:56 Christie Schumacher

There may benefit with Trulicity or Deeleglatide subcutaneous semaglutide or ozempic, and in Laryglotide, Victoza.

00:08:03 Christie Schumacher

These are all people that have had established cardiovascular disease or high risk for cardiovascular disease now.

00:08:10 Christie Schumacher

Based on the results of the cardiovascular outcomes trials, there have been other trials that have subsequently been done, such as, for example, step half PF looked at people that just only had obesity without diabetes and the benefit of the GLP one receptor agonist subcutaneous. The Meglotide on heart.

00:08:26 Christie Schumacher

Preserved ejection fraction.

00:08:28 Christie Schumacher

So we're starting to see some different studies come out that are looking at populations of people without diabetes.

00:08:33 Christie Schumacher

That don't high cardiovascular.

00:08:35 Christie Schumacher

And then they're just looking at how these agents work and more healthy individuals, so to speak, without diabetes, with high cardiovascular risk.

00:08:45 Sara Klockars

Thank you.

00:08:47 Sara Klockars

Are there specific GOP one receptor agonists that are more effective for Mace?

00:08:52 Sara Klockars

Is there a best one to reduce risk of Mace?

00:08:56 Lauren G. Pamulapati

Yeah. So when we think about Mace for our GLP agonist, the ones that have shown benefit are dalaglutide.

00:09:03 Lauren G. Pamulapati

Specifically the injectable format and lorazlotide. When we look at some of the other.

00:09:10 Lauren G. Pamulapati

So with like tirzepatide that trials ongoing and so we don't really have that evidence, although I would suspect it would be a hard sell.

00:09:17 Lauren G. Pamulapati

See that?

00:09:19 Lauren G. Pamulapati

But when we look at the other ones.

00:09:21 Lauren G. Pamulapati

Ezena tide. And when we used to have luxy xenitide on the market, those really showed neutral benefit. And so when you're thinking about your patients who have cardiovascular risk.

00:09:32 Lauren G. Pamulapati

You're really reaching for dalaglutide and semaglutide.

00:09:37 Lauren G. Pamulapati

From a prescribing perspective, really from ease of use as well. Obviously depending on formula as we'll get into, you might be reaching for loraglia tide for some of these patients depending on what they're able to get based on cost and availability. But really for me in my pract.

00:09:54 Lauren G. Pamulapati

For high end smart.

00:09:58 Sara Klockars

Thank you.

00:10:00 Sara Klockars

Christy, which diabetes meds reduce risk of heart failure exacerbations.

00:10:07 Christie Schumacher

Yeah. So the hdlt 2 inhibitors reduce the risk of heart failure hospitalizations. As many of you know, they're now recommended based on the 2022 ACCHA.

00:10:16 Christie Schumacher

Failure guidelines.

00:10:18 Christie Schumacher

As actually one of the four pillars for heart failure, reduced ejection fraction therapy.

00:10:22 Christie Schumacher

We really should be initiating sglc 2 inhibitors and people not only with diabetes, but also in.

00:10:27 Christie Schumacher

With heart.

00:10:28 Christie Schumacher

Right away, within their recent clinical.

00:10:33 Christie Schumacher

So they are now first line therapy for heart failure as well, just based on some of the original data that we've seen from the court evidence or outcomes trial and subsequent.

00:10:41 Christie Schumacher

Failure trials.

00:10:44 Sara Klockars

Excellent. And then when?

00:10:46 Sara Klockars

Say heart failure, can you just describe are we talking about heart failure with reduced ejection fraction or heart failure with preserved ejection fraction or both?

00:10:57 Christie Schumacher

Yeah. So we're actually talking about both for the pagal flog and our farceiga and an.

00:11:03 Christie Schumacher

So it's been interesting because historically there really haven't been any medications that have been shown to reduce hospitalizations for heart failure, cardiovascular death.

00:11:12 Christie Schumacher

In the heart failure, preserved ejection fraction population.

00:11:15 Christie Schumacher

Here we have two.

00:11:17 Christie Schumacher

The Pegophiles and the liver trial and then pegophilosine in the emperor preserved trial that showed a benefit in the preserved ejection fraction population.

00:11:26 Christie Schumacher

And then as far as the reduced ejection fraction, population dipego flows and pagal flows in as well showed benefit. However, if you look at the cardiovascular outcomes trials, what you see is in the subgroup analysis looking at heart failure benefit or in the secondary outcomes, you see that.

00:11:41 Christie Schumacher

All did show a trend in reducing hospitalizations for heart failure that was statistically significant.

00:11:46 Christie Schumacher

So all of the sglp 2 inhibitors did show that heart failure benefit in their cardiovascular outcomes trials, however with.

00:11:55 Christie Schumacher

They actually did not study it.

00:11:57 Christie Schumacher

Not available.

00:11:57 Christie Schumacher

You try to look up the data.

00:11:59

So that one.

00:12:00 Christie Schumacher

'S a little bit controversial because it is the most affordable sglt 2.

00:12:03 Christie Schumacher

So if you did need to use it, I would say you could probably assume a clash effect.

00:12:10 Sara Klockars

Great. Thank you.

00:12:12 Sara Klockars

That's a little bit of the data behind the scenes and now we're going to transition to what do we do with this data.

00:12:19 Sara Klockars

How do we apply it to our patients?

00:12:21 Sara Klockars

I'm going to pull in Stephen from a prescriber perspective.

00:12:25 Sara Klockars

And how do you decide which Med to prescribe first for your patients with diabetes?

00:12:31 Sara Klockars

Can you walk us through your decision making process?

00:12:37 Stephen Carek

Yeah, sure.

00:12:38 Stephen Carek

I'll try to cover my high points and obviously.

00:12:40 Stephen Carek

The goal is to individualize.

00:12:43 Stephen Carek

What is going to be best for the patient? What are they going to be able to remain on for long term for hopefully controlled over diabetes and definitely reduction in the risk of those cardiac events?

00:12:53 Stephen Carek

Or exacerbations, of their underlying chronic disease like heart failure. I think the first thing that I'll typically look at though is when I see a patient trying to decide initiate is what's a.

00:13:00 Stephen Carek

1C.

00:13:01 Stephen Carek

The reason is this is that if they are floly uncontrolled, like an A1C greater than 10, I'm really gonna be pushing for.

00:13:07 Stephen Carek

Go ones, maybe along at the insulin to help control their hyperglycemia with things like stld twos. I do worry about potentially the diuretic affect that they may have for those uncontrolled diabetics. You know that glucose, urea may cause dehydration.

00:13:23 Stephen Carek

Otentially unmask that you glycinic.

00:13:25 Stephen Carek

We talked about the urinary tract infections as well that in a that cause I tend to hold off on initiation of that unless they may have you know you know severe heart failure and already Max out another goal directed medical therapies.

00:13:38 Stephen Carek

Let's say their a.

00:13:38 Stephen Carek

1C is somewhere between that 7 to 10 range, which is really going to focus on what are those compelling indications? Are we trying to manage cardiovascular risk factors?

00:13:49 Stephen Carek

Are we trying to manage obesity?

00:13:51 Stephen Carek

Are we trying to manage heart?

00:13:53 Stephen Carek

I think this table lays out pretty.

00:13:55 Stephen Carek

Which one? You may or may not want to choose.

00:13:58 Stephen Carek

In my clinical practice, I probably say most of my patients that I see have.

00:14:03 Stephen Carek

Cardiovascular disease risk factors as well as obesity. And so I tend to start with the GOP one, but definitely those that have like heart failure, CKD are more likely going to lean towards initiation of sclt 2 for their management of their Type 2 diabetes.

00:14:20 Sara Klockars

Great. Thanks, Steven.

00:14:21 Sara Klockars

And are you adding metformin onto these drugs, or are you using metformin first?

00:14:30 Stephen Carek

Oh, that's a that's a really good question too. And I think one that's sort of seeing some evolving practices as well. I mean, it used to be metformin for everyone.

00:14:37 Stephen Carek

I'm slowly starting to eat in my own practice kind of preserve metformin, and it is so cheap for readily available.

00:14:45 Stephen Carek

Kind of minimal side effects for most patients that have like chronic kidney disease and at least kind of tolerate some of the initial GI side effects that I still tend to use.

00:14:52 Stephen Carek

32 bit esecially if they're A1CS are relatively again that 7 to 10 range, and there's so many cost barriers for patients that may have Jo one or maybe have indications for GLP one or SLT 2's?

00:15:04 Stephen Carek

It's a great cheap medicine still part of my kind of tool kit for managing.

00:15:09 Stephen Carek

Diabetes. I think these newer medicines, these GLP ones, sglt 2.

00:15:13 Stephen Carek

I mean, there's so many benefits and I think the effect of their benefits is really profound and significant and not only treating diabetes but preventing these cardiovascular endpoints.

00:15:22 Stephen Carek

That I'm starting to use them without metformin, articular for those patients that may have the means of getting it affordably, like insurance means or just have access to it.

00:15:33 Sara Klockars

Great. Thank you.

00:15:35 Sara Klockars

Lauren, do you have any other considerations or thoughts when you're recommending these medications for patients?

00:15:43 Lauren G. Pamulapati

I think Stephen really hit some of the high points. I mean, I really think you know, starting from the top like where he was talking about metformin and how you know, there are patients who when they come into your clinic and you're like, I would, you really need.

00:15:56 Lauren G. Pamulapati

Some glucose lowering and you also look at their past medical history and you see they have a strong cardiovascular history or a strong you start looking at their labs and you're like, hey, your kidney function is starting to decline, right?

00:16:09 Narrator

So.

00:16:10 Lauren G. Pamulapati

Starting to have that conversation with them and say, here's all of our options that we have. Here's the evidence. You know, we could.

00:16:17 Lauren G. Pamulapati

Start you on.

00:16:18 Lauren G. Pamulapati

We're going to get you a pretty decent A1C lowering depending on how far we titrate up that dose. You typically think about every 500 milligrams.

00:16:26 Lauren G. Pamulapati

Being about a .5%, a 1C lowering is still working your way up to potentially getting anywhere from one to two percent A1C lowering.

00:16:33 Lauren G. Pamulapati

Depending on where they're how far away.

00:16:36 Lauren G. Pamulapati

Goal, but as I start to see patients who have declining kidney function, I say well, this is really only helping us with one thing by doing metformin.

00:16:44 Lauren G. Pamulapati

Why don't we try to see if we can help you also preserve your kidney function and put you on an sglt 2 inhibitor?

00:16:51 Lauren G. Pamulapati

And so I think in that aspect, you're looking at just your oral options and can be an easy sell for some patients.

00:16:57 Lauren G. Pamulapati

But what I've really seen a ton of patients coming in is really looking for that weight management with the GOP agonist and especially when we are looking at our GOP agencies, not just helping with wheat and cardiovascular health, but really now the evidence with our kidney function as.

00:17:12 Lauren G. Pamulapati

You can really start to say like, why don't we really focus on three things for you and saying we're gonna really target all three of these issues that you have happening without adding on additional medications. And we can do it with just one injection a week. So I,

00:17:27 Lauren G. Pamulapati

That's really how you can start to.

00:17:29 Lauren G. Pamulapati

To tailor your conversation with your patients and really start to give them all the options.

00:17:35 Lauren G. Pamulapati

Think that's the most important? Is really laying out, you know, hear all your.

00:17:39 Lauren G. Pamulapati

Here are the risks and benefits of each and saying I often tell them if you were my parent, this is what I would probably.

00:17:46 Lauren G. Pamulapati

Recommend for you at this point and I that tends to really help in trying to relate to your patients and having them understand where you would be. And then with the metabolic liver disease.

00:17:55 Lauren G. Pamulapati

Thinking about mazel to mash and really saying that a lot of our patients.

00:18:00 Lauren G. Pamulapati

With diabetes have this liver disease and so how can we start to also impact this additional aspect of their care?

00:18:12 Sara Klockars

Great. Thank you.

00:18:14 Sara Klockars

I'm going to transition us over to heart failure and was hoping you could kind of walk us through when you would start an sglt 2 inhibitor for heart failure with reduced ejection fraction.

00:18:27 Sara Klockars

And then kind of.

00:18:28 Sara Klockars

Outline the differences for preserved ejection fraction.

00:18:35 Narrator

Of course.

00:18:35 Christie Schumacher

So really sglt 2 inhibitors now should be started right away for someone with heart failure, reduced ejection fraction.

00:18:42 Christie Schumacher

So you see here on this slide is the four pillars of heart.

00:18:44 Christie Schumacher

So the 8th Arbor, Arnie and Trusto, which is a combination of the Cubitral and valsartan.

00:18:50 Christie Schumacher

A beta blocker, aldosterone antagonist, or MRA, and in the GL2 inhibitor.

00:18:55 Christie Schumacher

So here what they recommend now in the heart failure guidelines is getting all four different medication classes on board just because they have different mechanisms of action that can improve the heart function and reduce hospitalizations for heart failure.

00:19:07 Christie Schumacher

So it is recommended to get the sglt 2 inhibitor on board very early in the disease progression now. So as soon as they have that heart failure diagnosis.

00:19:15 Christie Schumacher

And that would be, I would even consider that for preserved ejection fraction as well.

00:19:18 Christie Schumacher

We've been putting it on earlier and earlier and not waiting until the heart failure progresses or until their first hospitalization for heart failure.

00:19:26 Christie Schumacher

And then also too with reduced ejection fraction. I think there has been studies too that it's been beneficial to even start it at hospital discharge.

00:19:34 Christie Schumacher

Making sure their hemodynamically stable not dehydrated.

00:19:37 Christie Schumacher

You don't precipitate you glycemic Dec.

00:19:41 Christie Schumacher

However, just making sure they're stable and they can take it and it should be added on at the same time as like a spatula, mineral corticoid receptor antagonist to protect the heart.

00:19:51 Christie Schumacher

So for patients with heart failure preserved ejection fraction, we should be thinking about sglt 2 inhibitor therapy.

00:19:57 Christie Schumacher

So as I mentioned previously, with the deliver trial for DIPEOPLOS in and the Emperor preserved trial for Mpegophosen sglt 2 inhibitors have been shown to reduce cardiovascular death and hospitalizations for heart failure.

00:20:09 Christie Schumacher

In the preserved ejection fraction.

00:20:10 Christie Schumacher

So this is really starting to become the most robust data we have in this population. We've been. We know that historically preserved ejection fraction patients do tend to accumulate a lot of fluid, have severe edema.

00:20:22 Christie Schumacher

So we always want to make sure we're.

00:20:24 Christie Schumacher

Their loop diuretics.

00:20:26 Christie Schumacher

Recently, there's been some studies out with the non steroidal MRA, finer known which has shown benefit in the heart failure, preserved ejection fraction population as well.

00:20:35 Christie Schumacher

So that's another new tool in Venerinos marketed as kerndia. And then we also have been shown some modest benefit.

00:20:42 Christie Schumacher

With the cubitral, valsartan or Entresto.

00:20:45 Christie Schumacher

So we can consider that combination to cure Patrol Vulcan as well, especially beneficial in men with an ejection fraction less than 55 to 60 and then all women had better results with this succubatrevals valsartan.

00:20:58 Narrator

Trial.

00:21:01 Sara Klockars

Great. Thank you.

00:21:04 Sara Klockars

And I am going to transition us to this question that we've had multiple times from our subscribers and that's what's the role of combination therapy with the GLP one agonist with.

00:21:15 Sara Klockars

An sglt 2 inhibitor in patients so.

00:21:21 Sara Klockars

Boron, would you want to tackle that one?

00:21:25 Lauren G. Pamulapati

Absolutely. I use this all the time, so I feel like when you're first starting a patient, you think about what is their compelling indication and so are you choosing the GLP agonist or the sglt 2 inhibitor?

00:21:38 Lauren G. Pamulapati

But ultimately, most of these patients are going to require additional.

00:21:43 Lauren G. Pamulapati

Pharmacotherapy not just for their glycemic control, but when you start to think about all of the other benefits that we've already talked about today, right, the cardiovascular health, the kidney health.

00:21:54 Lauren G. Pamulapati

And the liver health, you start to say, why wouldn't I add this on?

00:21:59 Lauren G. Pamulapati

And so I'd say most of my patients, especially in my clinic who have long standing diabetes and we know what that comes, these cardiovascular and kidney disease, we're adding both of these all so they can get the most benefit from these medications.

00:22:13 Lauren G. Pamulapati

So I'd say, you know, absolutely, I think where you start just depends on patient preference, tolerability and really what their first initial compelling indication was.

00:22:23 Lauren G. Pamulapati

Again, thinking back to Stephen's comment about how far they are from goal.

00:22:27 Lauren G. Pamulapati

Would also help me determine, you know, am I starting the sglt 2 inhibitor versus the GLP agonist first and?

00:22:33 Lauren G. Pamulapati

You can get into some really healthy debates with people about, you know, personal preferences and where people choose to start, but I think ultimately it's just giving the patient.

00:22:42 Lauren G. Pamulapati

Their bonus over their own health and where they feel comfortable with starting based on maybe what they've talked about with their coat or their family members and really using them. But ultimately having that conversation of here's where I'm starting you today.

00:22:56 Lauren G. Pamulapati

This is what I'm thinking. You know, down the line, we'll probably add this on at some point.

00:23:01 Sara Klockars

Excellent. Teven, can you comment on the discussion you have with patients on combination therapy and what monitoring you ensure happens when patients are on both of these?

00:23:16 Stephen Carek

Yeah, totally. And and so I think just speak to some of some of our points where it's patients being on both of these, my typical communication them is they all have a respective job, some of them do some of these jobs better than others like GLP 1's.

00:23:30 Stephen Carek

With.

00:23:30 Stephen Carek

Weight loss.

00:23:31 Stephen Carek

So T2 S may be helping with preservation of kidney function, but ultimately these hope is that these are working well together and hopefully synergistically to help control your blood sugars and hopefully live healthier lives longer.

00:23:46 Stephen Carek

And hopefully prevent any of these cardiovascular events that we know of.

00:23:48 Stephen Carek

What are the main causes of morbidity mortality for patients with that?

00:23:51 Stephen Carek

Diabetes in terms of monitoring these therapies.

00:23:55 Stephen Carek

Specifically for things like GLP ones always keeping track of, I think wait is that that big.

00:24:00 Stephen Carek

Just you know, a lot of patients are very surprised by how much weight they can lose. These they do have a lot of patients who that you know, are sometimes disappointed by the amount of weight do they lose.

00:24:08 Stephen Carek

Of ties into maybe some of the lifestyle changes that they also have to participate in with this Medicare for some of those sort of biliary symptoms that patients.

00:24:16 Stephen Carek

Whether it's like Billy Kolek or Otentially sort of galbile related issues, articularly in kind of our female population that are on it for long.

00:24:24 Stephen Carek

Time resto 2 inhibitors, typically marketing electrolytes kidney function as well, making sure there's not sort of adverse electrolyte abnormalities or or decline in kidney function that could occur because of that kind of persistent over diuretic effect that these medicines may exacerbate.

00:24:40 Stephen Carek

Then, particularly for females as well, just talking about the frequency of maybe urinary tract.

00:24:45 Stephen Carek

Symptoms are they having more frequent or severe urinary tract infections? Fungal.

00:24:51 Stephen Carek

Kind of the secondary side effects that these medicines can cause, I can get rid of compliance and prevent them from want to kind of maintain these for a long period of time.

00:25:02 Sara Klockars

Thank you.

00:25:03 Sara Klockars

And transitioning to risk. So you mentioned several of them.

00:25:06 Sara Klockars

Lauren, are there other risks that you would warn patients about with SGLT 2 inhibitors and GLP 1 agonists?

00:25:15 Lauren G. Pamulapati

Yes, I think Steven had, you know, the ones that we typically start with, the one when we think about their genital, urinary infections and really I think that goes back to getting a good history with your patients too to say what has been your history with yeast infect.

00:25:28 Lauren G. Pamulapati

And just counselling on making.

00:25:31 Lauren G. Pamulapati

You know good general hygiene.

00:25:33 Lauren G. Pamulapati

Especially some of our older population, if they have any urinary.

00:25:37 Lauren G. Pamulapati

Like inability.

00:25:38 Lauren G. Pamulapati

Get to the bathroom on time and they have, you know, wet underwear saying, like, making sure you're changing out of any wet underwear or urinary pads and then talking about, you know, you can treat this over the counter, but also like letting them know that.

00:25:50 Lauren G. Pamulapati

Here for them, if they needed to have a medication on board.

00:25:54 Lauren G. Pamulapati

And saying, hey, you know, there might be a point where there isn't, you know, a line in the sand, at which point we would stop your sglt 2.

00:26:01 Lauren G. Pamulapati

Inhibitor but we could have that conversation if it got to that point.

00:26:04 Lauren G. Pamulapati

The other thing I think about is you glycine.

00:26:07 Lauren G. Pamulapati

So just making sure if our patients are getting sick, talking to them a little bit about.

00:26:11 Lauren G. Pamulapati

Sick.

00:26:12 Lauren G. Pamulapati

Management. And so if they're having any volume depletion, any vomiting or diarrhea or if they have profound weight loss.

00:26:19 Lauren G. Pamulapati

We typically think about a three kilograms in two days.

00:26:22 Lauren G. Pamulapati

Making them understand that they should stop the medication until they're able to resume eating and drinking at their normal pace for at least 24 to 48 hours. And if there's anything that's happening that's causing them to not be able to keep.

00:26:36 Lauren G. Pamulapati

Fluids or food down for 72 hours to give us a call so we can talk to them about their management of their sglt 2 and have.

00:26:43 Lauren G. Pamulapati

And then thinking about, you know, I think our inpatient team does a really good job of when patients are coming in for surgeries, about when to stop these medications.

00:26:51 Lauren G. Pamulapati

But really, making sure that when I see that a patient has an appointment scheduled talking to them as well about when you would stop your sglt 2 inhibitor.

00:27:01 Lauren G. Pamulapati

So three to four days before any of those surgeries to prevent any of your kidney damage or potentially for these patients with the glycemic decrease.

00:27:09

OK.

00:27:11 Sara Klockars

Craig and Christy, would you want to comment on risks with GLP one agonist use?

00:27:19 Christie Schumacher

Yeah. So with GLP one receptor agonist, I think the big thing is obviously they do increase the risk of nausea, vomiting.

00:27:26 Christie Schumacher

So counseling people to eat smaller, more frequent meals so they don't have those unpleasant side effects.

00:27:32 Christie Schumacher

Stop eating when they feel full.

00:27:34 Christie Schumacher

Overall, in general, possibly considering a more low fat diet to prevent some of that 'cause, we don't want those GI adverse events one to have them stop the drug 'cause we know the cardiovascular kidney benefit that they have is great.

00:27:46 Christie Schumacher

Overall, so we want to do the best we can to counsel people to make sure that they tolerate it very well.

00:27:51 Christie Schumacher

Also recommending to rotate injection sites preventing injection site.

00:27:55 Christie Schumacher

Proper counseling on how to administer the medication and as far as warning and precautions.

00:28:01 Christie Schumacher

Pancreatitis, we know that people that have had a history of pancreatitis are at higher risk for having it again.

00:28:07 Christie Schumacher

With the GOP one receptor agonist, we don't quite know what that risk is. Just because people with pancreatitis have been historically now removed from the trial as part of the exclusion criteria. When we look at GP1 receptor agonist. So in general it's a bit of a GR.

00:28:21 Christie Schumacher

Whether or not to start it in someone with a history of pancreatitis, it would depend.

00:28:25 Christie Schumacher

If we knew what that ideology of their pancreatitis was and how long it had been since they had an episode.

00:28:30 Christie Schumacher

Gallbladder disease. If they have a history of gallbladder disease, I do feel comfortable using it as long as it's not currently.

00:28:36 Christie Schumacher

Gallbladder disease. We want to avoid using these agents and patients with a history of medullary thyroid carcinoma and then also we have to be careful about pulmonary aspiration during anesthesia and sedation.

00:28:48 Christie Schumacher

This is a question we get asked a lot is should I?

00:28:51 Christie Schumacher

Glp one receptor agonist prior to my colonoscopy endoscopy, different procedure which would require anesthesia.

00:29:00 Sara Klockars

Excellent. Thank you.

00:29:02 Sara Klockars

Steven, what are some barriers or hurdles to getting patients on GOP antagonists or sgot 2 inhibitors or the combo that you see in your practice?

00:29:18 Stephen Carek

I think some of the barriers, I mean one barrier is just the GLP ones for the most part come injectable for all medication available. But in terms of the endpoints that we look for and I don't believe there's the evidence out there to support that yet, although I.

00:29:33 Stephen Carek

Feel optimistic that it hopefully will be.

00:29:35 Stephen Carek

But some patients are just have the needle phobia and the injections for those medications may just be a significant bearer for.

00:29:41 Stephen Carek

I think the other two broad ones that we will see are cost and insurance coverage depending on what a patient's hair source maybe can definitely influence the monthly cost and a lot of patient at least I take care of just don't have the means.

00:29:55 Stephen Carek

To afford these medications, if they are not covered under their insurance or part of some sort of charity.

00:30:01 Stephen Carek

I think the other thing too is just availability of these medications. We oftentimes hear of shortages, supply or shipping around having to order online, have to use compounding pharmacies. And so I think just the economics of these medicines just go in there in such high demand.

00:30:17 Stephen Carek

Has limited access for patients to take these and you have some patients that take them for maybe a month or two at a time and then join a shortage and aren't getting it for about 6 months and then get back on it. So daily and weekly monthly, Ann.

00:30:28 Stephen Carek

Use of that may be fluctuating depending on the patient as well.

00:30:31 Stephen Carek

Those are.

00:30:31 Stephen Carek

Of the main barriers to startup patient and there's other kind of medical issues talked about some of the getting a good history, understanding past medical history, some of the risk factors associated with medicines. If you talk with these patients about them, they may just be.

00:30:42 Stephen Carek

Of.

00:30:42 Stephen Carek

You know it.

00:30:43 Stephen Carek

Like a little bit too much for.

00:30:45 Stephen Carek

I already have, you know, for the year and year tract.

00:30:47 Stephen Carek

That's a big reason that several patients that I have won't want to take these medications.

00:30:52 Stephen Carek

Ollie Pharmacy is a big thing, I think with some of these medications for patients that may be on a sglt 2, maybe on the ACE or an arm and their kidney functions just trending in the wrong direction. While there's on these medications, we have to decide which ones.

00:31:04 Stephen Carek

Be best for them to continue on if they can continue and Toler.

00:31:08 Stephen Carek

Then then there's also a lot of information online about what these medicines may be.

00:31:12 Stephen Carek

Had several patients that are worried about the formula staying green.

00:31:14 Stephen Carek

A warning that.

00:31:15 Stephen Carek

Be on for SLT 2 some that are worried about the amputation risk that it's been sort of disproving gesture T.

00:31:21 Stephen Carek

So patients will come with their own kind of perceptions of what these medicines, the consequences, side effects of these may be that it's also potentially a.

00:31:29 Stephen Carek

For why they may or may.

00:31:30 Stephen Carek

Want to use these?

00:31:34 Sara Klockars

Excellent overview and Lauren, could you comment on the cost piece?

00:31:40 Sara Klockars

What are some strategies you use to help get patients on these medications due to this higher cost?

00:31:50 Lauren G. Pamulapati

Yeah. So you know, I think it's really looking at the formulary. And so you know for a lot of the GOP, when we started to have this shortage is when you really started to see insurance companies require the indication to clearly state that these patients had Type 2.

00:32:06 Lauren G. Pamulapati

And really making sure that the agent prescribed matches up with the FDA approved indication.

00:32:11 Lauren G. Pamulapati

For me, it's been a a little bit of trial and error.

00:32:14 Lauren G. Pamulapati

So sometimes it's like, OK, you know, one year one agent is approved on their formulary and the next year it's something else.

00:32:21 Lauren G. Pamulapati

And so trialing, you know, different agents for those patients, sometimes we work through all the options that are approved for them and those patients have failed or really maxed out some of their benefit from a glycemic perspective.

00:32:32 Lauren G. Pamulapati

So we have to, you know, to do a.

00:32:35 Lauren G. Pamulapati

Prior authorization to get them on something that may not be on formulary.

00:32:39 Lauren G. Pamulapati

I really also utilize a lot of patient assistance programs for these patients. Unfortunately, some of those were paused when the supply.

00:32:48 Lauren G. Pamulapati

Dropped and so a lot of patients, they weren't accepting new enrollments. And so that was really limiting for some patients to be able to get on these if they couldn't afford them.

00:32:55 Lauren G. Pamulapati

There's also copay assistance cards that can help patients who maybe have commercial insurance.

00:33:01 Lauren G. Pamulapati

But I think it's really just.

00:33:03 Lauren G. Pamulapati

I think making sure you're utilizing your networks of your professional network.

00:33:08 Lauren G. Pamulapati

So whether it's your organization's, you're a part of or you know, I'm familiar with Kristy.

00:33:13 Lauren G. Pamulapati

Being able to like text a friend and say what are you all using?

00:33:16 Lauren G. Pamulapati

You know, up where you are and like, how are you getting access to?

00:33:19 Lauren G. Pamulapati

I think that's really beneficial and just talking with people about how they're getting them. There is some evidence out there about.

00:33:26 Lauren G. Pamulapati

Extending and so I know the FDA doesn't or the package inserts don't necessarily approve micro dosing of some of these, but sometimes patients might be micro dosing and so there's some new evidence out there about still getting some benefit from micro dosing of the GLP organisms maybe extend.

00:33:42 Lauren G. Pamulapati

During times where patients might have an insurance loss or a lapse in insurance.

00:33:47 Lauren G. Pamulapati

For the sglt 2 inhibitors, I do think again really we have.

00:33:53 Lauren G. Pamulapati

The cheaper option so with lexical flows in and being able to get that for patients. So that still comes at a pretty high cost.

00:34:00 Lauren G. Pamulapati

So some patients can really only afford a few dollars a month. And so when you're looking at even, you know, 30 to $40 a month for a prescription and it's only one of them that can still be a huge barrier.

00:34:12 Lauren G. Pamulapati

Understanding that maybe they don't have it on their.

00:34:14 Lauren G. Pamulapati

At all, as so they can get it through that.

00:34:17 Lauren G. Pamulapati

And so that's one option with the sglt 2 inhibitors and then looking for some charitable.

00:34:22 Lauren G. Pamulapati

So where I am, we do have some pharmacies that patients can go to if they've lost insurance.

00:34:27 Lauren G. Pamulapati

So these pharmacies are getting medications through the manufacturers or through other donations, and they're able to.

00:34:35 Lauren G. Pamulapati

Get these patients these medications at.

00:34:37 Lauren G. Pamulapati

Low cost or no?

00:34:38 Lauren G. Pamulapati

However, it does require often switching patients, so I might be switching patients from 1 sclt to inhibitor to another based on what they have.

00:34:46 Lauren G. Pamulapati

And stop.

00:34:48 Sara Klockars

Great overview.

00:34:49 Sara Klockars

You.

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