Ryan Haumschild, PharmD, MS, MBA: As we talk about SGLT2s [sodium-glucose cotransporter-2 inhibitors] and GLP-1s [glucagon-like peptide agonists], a lot of our endocrinology colleagues are familiar with these medications. And so, Dr Green, I’d like to pose this question: the SGLT2s or GLP-1s, what role do they play in the current treatment landscape for patients with CKD [chronic kidney disease]? What are some of the most common regimens that are used for initial management? If we could start there, that would be great.

Jennifer B. Green, MD: Well, there’s a difference between what’s most commonly used and what the guidelines say.… So I’ve been very closely involved with the development of guidelines or the evolution of guidelines for the care of patients with type 2 diabetes and chronic kidney disease…. The American Diabetes Association [ADA] guidelines very clearly say that if…a patient has type 2 diabetes and any evidence of chronic kidney disease, has an eGFR [estimate glomerular filtration rate] of less than 60 or any degree of elevation…sustained for 3 months or longer, they should be on an SGLT2 inhibitor as well as their RAAS [renin-angiotensin-aldosterone system inhibitor]. But SGLT2 inhibitors should be part of their foundational therapy, primarily to reduce the risk of progression of kidney disease and to reduce the risk of major adverse cardiovascular events, including heart failure. It’s important to remember that the recommendations are that if such a person has an eGFR of 20 or greater, they should start the SGLT2 inhibitor. People used to be [think] that if the eGFR was too low, you shouldn’t use it. In fact, those patients benefit most and they should stay on the SGLT2 inhibitor until they need dialysis. Of course, some patients will need to stop earlier than that for individual reasons, but the recommendation is for them to stay on it until dialysis is required. So these are foundational medications now in the diabetes care guidelines. The GLP-1 question is interesting. There [are] data to suggest that in similar patients the GLP-1 receptor agonists may have a kidney benefit as well, but the data so far have most clearly demonstrated that they tend to slow the worsening of urine albumin-to-creatinine ratio increase, so they slow the progression of albuminuria. There are studies ongoing that will look a bit more carefully at the effects of GLP-1 receptor agonists in chronic kidney disease. So we may learn more in the current ADA guidelines. The GLP-1 receptor agonists are recommended for risk reduction as an alternative to SGLT2 inhibitors of a patient with diabetes and chronic kidney disease [who] can’t take an SGLT2 inhibitor for some reason. The GLP-1 receptor agonist could be used primarily to reduce their risk of cardiovascular events. And the ADA also recommends that if a person on one of the drugs—for example, an SGLT2 inhibitor—needs additional glucose lowering, then you could certainly add the GLP-1 receptor agonist as the next step. We don’t recommend at the present time that both classes be used in patients with chronic kidney disease to improve cardio-renal outcomes. But that may be simply because we’re missing important information and we don’t know enough yet to clearly say that 2 drugs are better than 1, from an outcomes perspective. So there’s so much to say here…. It’s important to remember that if you have type 2 diabetes and your eGFR is below about 40 or 45, if you start that SGLT2 inhibitor, your blood sugar isn’t going to come down very much. [They’re] not effective glucose-lowering medications at that range, but it doesn’t matter. It’s still going to reduce your risk of cardiovascular events and progression of kidney disease…. But remember, if that patient needs significant glucose lowering, you’re not going to accomplish that with the addition of the SGLT2 inhibitor. So you’ll need to do multiple things really to address all of that patient’s needs.

John E. Anderson, MD: And one of the things…she’s developed and worked on all of these guidelines. It has been a big focus in the endocrinology world and in primary care of trying to change from that glycemic-centric focus and understanding. Because as the ADA [guidelines state], it doesn’t matter what your agency is. It doesn’t matter what your glycemic control is. Even if you have tight glycemic control and you have CKD or heart failure or ASCVD [atherosclerotic cardiovascular disease], there are guideline-directed classes of therapies you must be using. It’s been a big part of educating all of those people who take care of [patients with diabetes] that you have to think differently now. And if you’re not, you’re not affording your patient maximum risk reduction.

Jennifer B. Green, MD: And you know, I forgot to answer one of your questions and that was about what’s happening in clinical practice. Well, what’s happening…is that almost everybody is on metformin, and it takes a long time for patients to move beyond that, even when they have very clear indications. Remember that these beneficial medications are recommended for higher-risk patients, irrespective, of course, of whether they need additional glucose lowering and also irrespective of whether they’re on metformin. So it doesn’t have to be metformin first. For example, if a patient with cardiovascular or kidney disease is then diagnosed with diabetes, you can go right to the drug that provides glucose lowering and an outcomes benefit.

Ryan Haumschild, PharmD, MS, MBA: …A lot of our managed care colleagues might have a step-through therapy of metformin. And so what if a patient does have preexisting conditions and maybe SGLT2 is the best agent for both? How do you get access to that earlier in the treatment pathway? I think of that and psoriasis and other medications where maybe an IL-23 is better for patients with metabolic syndrome and psoriasis, but they can always get there because there’s a step edit. I think that’s a really important takeaway. How do we design treatment pathways that are unique to each patient based on their condition? …One of the biggest things we’ve heard throughout this discussion is that guidelines recommend SGLT2 therapy for these patients. However, for a number of patients where this is indicated, a lot of providers are not starting patients. Why do you think that is and what can we do to improve that?

Jennifer B. Green, MD: Well, there are many reasons why guideline-based therapies are not prescribed, and I don’t know that we have enough time to go into all of them. But the biggest problem is simply clinical inertia and getting people to do something new and different that isn’t part of…their practice or care pathway…. So it’s hard to do something different. It takes a little bit more time to start somebody on a new class of drug and talk about the cost and what the potential [adverse] effects might be. But it’s incredibly important to spend that extra few minutes because maybe you will prevent that patient from needing dialysis for the remainder of their life. So it’s worth the time. There [are] issues related to access, and those will probably get better in the relatively near future as we expect to have at least 1 generic SGLT2 inhibitor available in the foreseeable future. But some of this is just a matter of people understanding…what the clear benefits are [in using] these newer medications, and just making it part of their routine. I would encourage people who are not prescribing, for example, the SGLT2 inhibitors on a regular basis for your patients with kidney disease —just get started. Do it a few times. I mean, generally, you see it all goes well. There are no major issues. You have to dip your toe in the water so that you can become comfortable with it and make it part of your standard practice.

Ken Cohen, MD: And Ryan, this is another really important area where population health management approaches can be beneficial. So OptumHealth, for example, takes care of 22 million patients. We can take all 22 million patients and we can look at their comorbidities. If they have a diabetes diagnosis, bump it against their pharmacy claims and identify the subset of patients who are not on SGLT2 who should be. We can then present individual lists of patients to the clinical pharmacists for each of these groups. Again, take this out of the hands of the PCP [primary care physician], and those clinical pharmacists can then look at the drug regimen for any given patient and make recommendations, depending on the circumstances, directly to the patient or to the PCP or where the pharmacist has been giving prescribing authority to change the drug regimen.

Ryan Haumschild, PharmD, MS, MBA: It’s a great use of data really for population health. But I think for the patient, if you have a pill that’s doing that work, that’s complementary to your provider team. I think at the end of the day, it’s kind of superior care and I think that’s the kind of partnership that a lot of people are excited about from payer colleagues, especially those with millions of covered lines where they can complement the practice, not fill in the gaps based on the claims data that they’re seeing come through.

Transcript is AI-generated and edited for clarity and readability.