SGLT2 Inhibitors and GLP-1 Agonists Have the Potential to Change the Type 2 Diabetes Treatment Paradigm. Will That Be Embraced?

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Javed Butler, MD, MPH, MBA, discusses the 2018 American College of Cardiology Expert Consensus Decision Pathway, which includes guidance on the use of SGLT2 inhibitors and GLP-1 receptor agonists, and its potential to change the treatment paradigm for patients with type 2 diabetes.

The 2018 American College of Cardiology Expert Consensus Decision Pathway (ECDP) directly addresses the positive results seen with the use of sodium—glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in the reduction of the risk of major cardiovascular events in patients with type 2 diabetes. It provides “succinct, practical guidance” on the use of these agents for “reducing CV risk in patients with type 2 diabetes and clinical atherosclerotic cardiovascular disease,” according to the guideline authors.1 Recently, The American Journal of Managed Care® (AJMC®) spoke with Javed Butler, MD, MPH, MBA, chairman and professor, department of medicine, The University of Mississippi Medical Center (UMMC), in Jackson, Mississippi, to discuss the implications of this new decision pathway.

[Editor’s note: Transcript has been modified slightly for readability.]

AJMC®: Since the publication of the ECDP, have you seen or experienced increased collaboration among your endocrinologist, cardiologist, and primary care colleagues to jointly manage patients with comorbid type 2 diabetes and atherosclerotic cardiovascular disease?

Butler: Not yet. The document was only published a few weeks ago and so we do not expect it to change the culture of medical practice [that rapidly]. The document gives us a resource, backed by professional societies, that we can use to create initiatives [to collaborate] with the primary care physicians and endocrinologists, and it highlights why collaboration among these providers is so important. This will lead to more collaboration in the future.

In Mississippi, where I practice, we have the second highest rates of obesity,2 diabetes,3 and cardiovascular risk4 in the nation, and the cardiovascular outcomes are not optimal. Initiatives like these help me to energize my colleagues. [The cardiologists at UMMC] have good relationships with our nephrology and endocrinology colleagues, but [the publication of the ECDP] has garnered a lot of attention around how we can do things together.

For example, we recently started discussing the feasibility of 2 new initiatives [following the publication of these guidelines]. The first is the creation of a patient-centered cardiometabolic clinic where, rather than seeing 2 or 3 different specialists over the course of several months, patients with comorbid conditions can instead come to a cardiometabolic hub where all the specialists are located. There we can have joint programs and management strategies.

The second, larger initiative that we are discussing, considering that Mississippi is the poorest state in the nation,5 is one to increase access to care. Many patients in our state have problems accessing care, especially those who come from the Mississippi Delta and outlying areas, through Jackson. Our goal with this initiative is working on maximizing their access to care through telehealth. We are hoping to learn whether telemanagement of cardiometabolic diseases can be successful, based on some of the recommendations and more considerations that we are continuing to develop.


AJMC®: How are you considering implementing the use of new SGLT2 inhibitors and GLP-1 agonists in your facilities when they are known to be expensive medications and you are working in one of the poorest states?

Butler: We need to think in terms of advocacy, and community and population health, as well as 1-to-1 interaction with the patient in the clinic. For example, our telehealth initiative focuses on solving a health systems—related issue; however, we also need to work with advocacy groups and the pharmaceutical industry and insurance companies to help solve access to care. We can debate the molecular ins and outs of the different SGLT2 inhibitors and GLP-1 agonists, but the bottom line is that providers need at least 1 option in each category. If we could at least get 1 SGLT2 inhibitor and 1 GLP-1 agonist covered and on the formulary, that would be something.

Another part is changing the culture to embrace shared decision making. Our assumptions about what a patient can and cannot afford [have to change. Typically,] we prescribe the cheapest medication to the patient because of an assumption, which is the right thing to do if 2 options are equal in their benefit and risk. I understand that the patient may have multiple different comorbidities and they may be taking multiple different drugs that they may not be able to afford, but I do not think that I should be making the decision for them. The patient should be making the decision and I should be informing them of benefit, risks, and costs.

For example, I am a heart failure cardiologist and right now there is a great deal of discussion over [a certain drug] being significantly more costly than an alternate option of using an angiotensin-converting-enzyme (ACE) inhibitor. Many of my colleagues say that they prescribe an ACE inhibitor because their patient cannot afford [the other drug]. Therefore, I ask them to at least talk to the patient. I ask them to tell the patient that, “This drug provides a 20% better chance than an ACE inhibitor that you will live longer and not have to come into the hospital. On your insurance, the ACE inhibitor is [for example] $15 per month and this drug is [for example] $45 per month.” Then, if the patient states that they cannot afford [the more expensive option], that is perfectly fine. However, I do not think that I should be the one to make the decision for them, without letting them know. [If I do not tell the patient] they may never know [that there is another option available], and so we should let the patient choose the drug.

Accomplishing this shared decision making is more difficult [than it sounds]. I am cognizant of the fact that clinicians need to move patients through [their appointments] in less than 20 minutes, so you cannot have a 30-minute discussion with every patient about all these points. However, this is 2019; there are other things that you can do. You can give patients iPads [with this information] when they are sitting in the waiting room; you can provide printed materials; you can hold group classes with nurses giving this information to a group of patients and the doctors can speak with them individually just to answer their questions; we can mail this information to patients, etc. All these things are doable; we just need to have the will.

AJMC®: What are the next steps to guide decision making around SGLT2 inhibitors and GLP-1 agonists?

Butler: There are many next steps. One step involves further research. So far, we have studied the middle of the spectrum population of patients with either risk factors for or known atherosclerotic cardiovascular disease. We did not take the sickest of the sick patients, the patients with heart failure, to see the effect of these drugs. Now there are several clinical trials7-10 being conducted with the SGLT2 inhibitors in patients with heart failure and so evidence will mount to see if we can go further down the spectrum of risk to see if these drugs help or not. We can also go upstream with the risk looking at using these drugs in patients without atherosclerotic cardiovascular disease or other risk factors, (eg, those patients with new onset diabetes who are about 35 years old).

Another step involves better utilization of the data that are already there. Guidelines across specialties have to be written and harmonized. This is a pet peeve of mine: Cardiologists, and endocrinologists, primary care practitioners, pharmacists, nurse practitioners—whoever is going to be touching these patients—all have different guidelines. We need to change our mindset. Not everyone can have time to argue and understand the subtle differences in their guidelines. The bottom line is that we are all working with the same patient and using the same evidence. Problems arise when the team players are not on the same page. With the arrival of these new drugs, the information should be harmonized when they are added into all the guidelines.

The third step is the dissemination of the message about these new treatments and guidelines. We are in the midst of an interesting dynamic shift in mindsets among specialists. For the past several decades, endocrinologists were glucose-centric and focused on drugs to treat glucose and not cardiovascular risk in patients with type 2 diabetes. They know the data on cardiovascular risk, but it is not in their routine practice to worry about them as much as a cardiologist. That is slowly changing. On the cardiology side, it has been in our DNA to worry about cardiovascular outcomes, but not in our DNA to think about diabetes as a modifiable separate risk factor; we still go toward giving statins and aspirin, etc. As the mindsets are changing, both of these groups have to meet in the middle and consider both aspects of the patient’s health.

That game will really be won, though, when we are able to convince our primary care colleagues to also focus on these issues. Massive education and awareness campaigns need to happen [to include this group] because we will not make a dent in human suffering until these recommendations are translated to the care of the patient. That will require all the avenues that we have available, such as continuing medical education, society collaborations, scientific meetings, etc.

The fourth step is to create systems of care. The healthcare community needs to become more patient-centric. The current healthcare system is not patient-friendly, and something has to change.

This process for change is a 5- to 7-year time horizon, not a 2-month time horizon. We need to understand, though, that the 5- to 7-year time horizon becomes a 10- to 12-year time horizon if we do not take the first step.

I know that it sounds daunting, but we have done this before. For example, when I was in medical school, beta-blockers were contraindicated in patients with heart failure. Then, clinical trials6 were completed [which brought new evidence] and we had to switch our mindsets from “These drugs are bad for you” to “These drugs are actually good for you.” Now, if you look at the data, more than 90% of patients with heart failure are on a beta-blocker. Over the span of about 10 to 12 years, we completely shifted the paradigm. [We showed that] it’s doable to shift the mindset in healthcare if you have the willingness.

AJMC®: What is coming down the pike that you are most excited about with regard to these new treatments?

As a heart failure transplant cardiologist, I am most excited about the clinical trials that are in process with the SGLT2 inhibitors in patients with heart failure. Current heart failure data with patients and SGLT2 inhibitors largely target prevention of heart failure, but if you look at the pharmacodynamics of SGLT2 inhibitors, the benefit profile is such that they could potentially benefit patients who already have heart failure, irrespective of whether or not they have diabetes. These data will come out between 2020 and 2021 and I am extremely excited to see these results.


Javed Butler has received research support from the National Institutes of Health, Patient Centered Outcomes Research, and the European Union. He serves on the speaker bureau for Novartis, Janssen, and NovoNordisk, and serves as a consultant and/or on the steering committee, clinical events committee, or data safety monitoring boards for Abbott, Adrenomed, Amgen, Array, Astra Zeneca, Bayer, BerlinCures, Boehringer Ingelheim, Bristol Myers Squib, Cardiocell, Corvidia, CVRx, G3 Pharmaceutical, Innolife, Janssen, Lantheus, LinaNova, Luitpold, Medscape, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, StealthPeptide, SC Pharma, V-Wave Limited, Vifor, and ZS Pharma.


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