How Recent Developments Impact Insulin Affordability

Insulin for All?

You have a medication where you have an indication for type 2 diabetes, an indication for prevention of heart failure, an indication for treatment, and now an indication for CKD [chronic kidney disease], and a couple of those indications regardless of diabetes status. Whose responsibility is it now? Where do you start? I’d love both of your perspectives. You’re going to see a patient with heart failure who also has some of the others, and you’re going to see a patient with diabetes who also needs help with heart failure or CKD. How do we sort this?

 It’s everyone’s responsibility. Whose responsibility is for the statin? If I see the cardiologist’s patient and I want to be more aggressive with their lipid management, I’ll do it and put it in my note to them and vice versa. If the cardiologist is seeing my patient, I hope they would be aggressive and initiate the SGLT2 if it helps the patient. Whoever is lucky enough to see that patient should do it and not keep putting it off, otherwise the patient suffers.

 I completely agree. The overlap and these disease domains are so far-reaching that every clinician should become comfortable with initiating, continuing, and managing SGLT2 inhibitors. Specifically, similar to statin and ACE inhibitors and ARBs, the indications are so frequent, we need to identify patients who don’t meet indications for starting these therapies. Because of that and the cost implications of the system, we need to think broadly about first making sure our highest-risk patients are on therapy: those at risk for early progression or who have already established disease.

Unfortunately, there are large gaps there that still need to be filled, and earlier on in the disease. For instance, type 2 diabetes with multiple risk factors. For instance, with a naïve patient with type 2 diabetes who’s newly diagnosed, it’s difficult to understand where SGLT2 inhibitors should fit in. Once they become more affordable and accessible on a broader scale, we can think of them similar to statins and ACE inhibitors, so most of us feel comfortable starting them in patients most at risk for progression.

Speaking of ACE and ARBs, those are the traditional ones we’ve used. We have the SGLT2 class now, and Dr Busch, you mentioned we have other ones in the pipeline, such as finerenone. How do you start to incorporate these additional classes? I’ll be honest. When you put a patient on an ACE or an ARB, I’m documenting in my notes and it says patient is on maximum tolerated ACE or ARB, blood pressure is rate limiting, potassium is maybe a rate-limiting step, and that’s where we stop. In many cases, I don’t know if we even check the follow-up after that, because what’s the point? As you mentioned, we could probably count a handful of times you order 1 to begin with.

What do we do now? Do we start thinking of it like diabetes, where there are multiple medications and we’re trying to hit the different core defects of the ominous octet in different ways, the same way we have heart failure and these 4 pillars? What are your initial thoughts in any best practices that we can think of as we add more tools in the toolbox from a CKD standpoint? Dr Busch, I’d like to start with you.

 When I was recruiting for these studies from data mining, a lot of my associates didn’t order urine microalbumins once the patient was on a RAS blocker because they figured, “What more could I do?” I couldn’t recruit them in the study because I didn’t want to have screen fails. You’d screen fail if the urine microalbumin was too low. I mandated, and it’s in the guidelines to do a urine microalbumin at least yearly in someone with diabetes. What we did for the practice benefit—not for the benefit of recruiting patients—that everyone who had to have a urine microalbumin for a year, we mandated a urine microalbumin to be done in the lab.

By doing that, we found a lot of patients who had high urine microalbumin. We wouldn’t have known they had it because they were on the RAS and the clinician thought, “I’m protecting their kidneys. I’m not going to give an x-ray dye. No NSAIDs; they’re on a RAS. Goodbye, I’m done.” The other frustration is they weren’t on maximal dose of RAS. We have our PharmDs enforce this to maximize the RAS if it’s possible if the potassium isn’t going up and the blood pressure isn’t too low.

When you add an SGLT1, you might lower the blood pressure a little. First, if they’re on a thiazide, I usually get rid of the thiazide. The SGLT2 has blood pressure efficacy similar to a thiazide diuretic; not like a loop diuretic, which has more diuretic effect. If their blood pressure is lowish to start with, I might move the RAS blocker to bedtime to make room for the SGLT2 so it will have that much of an antihypertensive effect. The other thing is the creatinine can bump a little. You get the GFR [glomerular filtration rate] dips a little, and it stabilizes. Just as we lived through this with RAS blockers that you tolerate a 30% bump of creatinine, it’s a similar rule of thumb with an SGLT2. Don’t worry. People who know they have kidney disease get very worried if their GFR drops an iota. If the GFR goes even from 45 to 43 mL/min, they’re worried. “Oh my god, I’m heading to dialysis.” You have to reassure them that it drops and then stabilizes.

 That point needs to be reinforced over and over again. That correction of hyperfiltration is the core defect that’s corrected for each of these therapies: the renin-angiotensin system inhibitors, the SGLT2 inhibitors, and the selective nonsteroidal MR antagonist. The correction of hyperfiltration all leads to a predictable decline in eGFR [estimated GFR] early on therapy and then stabilization. That can almost be a pathway because initiation of each is going to result in almost identical eGFR dips. That should be an anticipated dip that shouldn’t lead to any clinical action.

In fact, in many cases, especially for the SGLT2 inhibitors, there may be little rationale to do follow-up testing of a basic metabolic panel early after initiation because they, unlike renin-angiotensin system inhibitors and finerenone, do not have a hyperkalemia risk. In fact, they help lower hyperkalemia. Because of that, the rationale for checking a laboratory result that you’re not going to act on is a little uncertain. In my practice, I waited with patients with chronic kidney disease especially, allowed the eGFR to stabilize and then, at their next clinical appointment as a part of routine care, I checked laboratory studies.

That makes a lot of sense. I started explaining it to the patients the same way when we use multiple diabetes medications to attack the problem, the same way you use hypertension medications. You might be on 2 or 3, and now we’re starting to do this. We didn’t have those options, but now that we do, it’s another great advancement in the CKD arena and also for our patients.

Videos

Robert Busch, MD, and Muthiah Vadugananthan, MD, MPH, share their thoughts on the multifunctional responsibility of managing a patient’s renal disease.

Managing Renal Impairment with Multiple Agents

Dr Busch, you’ve had a front-row seat. You’re an investigator in the Dapa-CKD trial. You saw what happened there. You saw the final label. One of the things that was intriguing in looking at that was the indication. Unlike prior ones, it wasn’t based on a certain cutoff. You have anyone that’s at risk of progression. To me, that’s pretty much anyone, right? All of us are at risk of progression, so to speak. Help me understand how you’re understanding that indication and how you’re talking to your peers about that. Depending on what continuum you sit, you might not be seeing those patients until they’re more severe. The way it’s written, this therapy can be very valuable even for patients who are on the mild to moderate side. What was your reaction to it, and how are you disseminating this information to your peers and colleagues?

 It’s a very generous label because with canagliflozin in CREDENCE, it was the study criteria, urine microalbumin over 300 mg/dL. Even though in this study, you had to have 200 mg/dL. The FDA was so impressed with the data and the 39% lowering of the composite end point for renal protection that they don’t have proteinuria in the label. As you mentioned, it’s who’s at risk for progression of kidney disease. It’s like beauty is in the eye of the beholder. If you think your patient is at risk, the GFR [glomerular filtration rate] could be higher than 60 or 70 mL/min, but they have proteinuria. Or they could have a GFR without proteinuria, but they’re at risk of getting worse. Those are the types of patients.

It’s a very generous label. You don’t just have to have diabetes. Even in a hypertensive patient who has some urine microalbumin present, whose GFR is in the 50s mL/min, that’s a patient who’s also at high risk to progress toward dialysis. That’s someone for whom you’d also want to slow down things, with not only a RAS blocker but going beyond that with dapagliflozin.

 I agree 100%. Both CREDENCE and Dapa-CKD had average UACRs [urine albumin-to-creatinine ratio] of about 1000 mg/g, based on the relative cutoffs. The FDA labeling, the documents, and the discussion during the advisory committee reflected on the parallel experiences between DECLARE-TIMI58 and Dapa-CKD, where you have a continuum of low-risk patients with type 2 diabetes who are at risk for progression, and then more advanced patients with established albuminuric kidney disease. There’s no heterogeneity in treatment effects across that spectrum based on UACR. That was the rationale behind not including it in the label.

In practice, that removes a substantial barrier to use because albumin-creatinine ratios are often not measured. Sometimes there aren’t even structures in place to measure them. For instance, in a cardiology clinic, I could probably count the number of times we’ve measured UACR. It’s an extension beyond the trial, for sure, but it borrows on adjacent disease states and trials that have studied the exact same compound.

Dr Robert Busch and Dr Muthiah Vadugananthan provide insights on educating their peers on the importance of decreasing renal progression.

Importance of Education on Reducing Renal Progression

Dr Busch, can you talk to us about what we’ve had available to us as we manage CKD [chronic kidney disease] in patients with type 2 diabetes? We’re getting to a point where it’s not just patients with type 2 diabetes who can benefit from this. Could you talk to us a little about some of the options, risks, and complications that we’re trying to mitigate with this additional pharmacotherapy?

 Until fairly recently, all we had were the ARB trials with RENAAL and the Irbesartan Diabetic Nephropathy Trial. If you recall, this came out the week after 9/11, so in 2001, it showed it lowered end-stage renal disease by 16%. What we don’t recall is there’s still huge persistent renal disease. It lowered it, but it’s still 40% in the treated groups, so we can still do a lot better. Many trials have been done with other drugs that were unsuccessful. When the SGLT2s were studied in the cardiovascular [CV] trials, interestingly, each of the trials showed a renal composite that was beneficial in terms of lowering dialysis or lowering GFR [glomerular filtration rate]. But they didn’t get the indication until dedicated renal trials were done.

The first renal trial was the CREDENCE trial with canagliflozin. They took patients whose urine microalbumin were over 300 mg/dL and GFR 30 to 75 mL/min. This trial showed that it lowered renal composite by 30%. Canagliflozin had the label that in a patient with type 2 diabetes with urine microalbumin over 300 mg/dL; they can be on canagliflozin 100 mg until they’re on dialysis. It lowered the high-speed train to dialysis. Instead of going down rapidly, it would level it off.

Dapagliflozin was studied in patients who did and didn’t have diabetic nephropathy. You had type 2 diabetes or patients with other types of nephropathy from hypertension or other illnesses. GFR there was 25 to 75 mL/min, urine microalbumin over 200 mg/dL, and the trial was stopped early. In 2.4 years, it ended up lowering end-stage renal disease 39%. This was on top of the RAS blocker. The patients were on a RAS, and this was on top of that. Then the EMPA-KIDNEY trial is still ongoing. In that study, they have GFR down to 20 mL/min with no requirement for proteinuria. We’ll see what goes on there.

Finally, a study has come out called the FIDELIO-DKD trial with the drug finerenone. It’s an aldosterone blocker but different from the other standard aldosterone blockers. In that trial, giving it on top of a RAS blocker in patients with diabetes lowered end-stage renal disease 18%. That drug isn’t on the market, but it’s soon to be. We’re going to have a whole array beyond ARBs that will benefit patients. So it’s no NSAIDs [nonsteroidal anti-inflammatory drugs], no COX2s, avoid dye studies, keep well hydrated, raise your ACE or ARB, raise your SGLT2, and maybe down the line raise your finerenone.

Excellent. As we hear from the cardiology perspective, I have a question. I know I’m in this boat. I don’t think we really appreciated the CV risk that exists in patients with CKD and renal impairment. Now that we’re hearing more about the MRA [magnetic resonance angiography] and other options, and we’re starting to see the SGLT2 data, it’s been more front and center. If you can, talk about the CV risk there. We talk about it in diabetes, but we fail to talk about it. Maybe it’s because we never had anything that we can do for that. If you could shed some color there.

 Absolutely. Unfortunately, cardiovascular disease is the leading cause of death among patients with chronic kidney disease, especially among those who progress to end-stage kidney disease. As we learn more, there’s no coincidence that the progress made in heart failure with reduced EF [ejection fraction] to identify 4 pillars of therapy have striking overlap with emerging pillars for chronic kidney disease, inclusive of renin angiotensin system inhibitor, MR [mineralocorticoid] antagonist, and an SGLT2 inhibitor. Three of the pillars are common to both disease states. That highlights the overlap in clinical practice of these conditions and the common disease mechanisms that facilitate ultimate disease progression and clinical events in practice.

We’re learning much more. I see so many parallels with what has happened in heart failure care where we have a long drought in therapeutics and then rapid progress. Very soon, we’ll be having identical conversations about how to implement multiple therapies. Short of definitive clinical outcomes, there are really promising data with the GLP1 receptor agonists in slowing albuminuria especially, as well as safely lowering and improving glycemic control, even in advanced CKD. There are also investigational therapies, such as an endothelin receptor antagonist called atrasentan, which also similarly improved renal risk in patients with chronic kidney disease. A multitude of therapies are coming to the forefront of care. Chief among them are those that modify cardiovascular disease pathways. It’s an exciting area ahead.

An expert endocrinologist and cardiologist discuss the risks and complications of renal disease associated with diabetes and cardiovascular disease. Dr Robert Busch also provides an overview of some of the studies done in renal impairment.

Risks and Complications for Chronic Kidney Disease

 program titled “Management of Diabetes and Renal Impairment.” I’m Dhiren Patel, an adjunct associate professor of pharmacy practice at the Massachusetts College of Pharmacy [and Health Sciences] in Boston, and an endocrine clinical pharmacy specialist. Joining me in this discussion are Dr Robert Busch, the director of clinical research and a practicing endocrinologist at the Albany Medical College Faculty Practice in Albany, New York; and Dr Muthiah Vaduganathan, a cardiologist at Brigham and Women’s Hospital and faculty at Harvard Medical School in Boston, Massachusetts. Thank you both for taking the time to be here today.

One thing we’re increasingly finding out in patients with diabetes is that it’s no longer just about diabetes. There’s a long list of comorbidities we need to take into consideration. I always say that I don’t know the last time I saw a patient who had only diabetes and I didn’t have to go through their past medical history and factor in 3 or 4 different things as I decide how to counsel that patient and what pharmacotherapy to consider. Dr Busch, can you talk a little about the prevalence of renal impairment? This is something we’ve always talked about from the beginning days where we’ve had to keep an eye on the patient’s eGFR [estimated glomerular filtration rate] as we think about drug therapy. What are you seeing in terms of the prevalence of CKD [chronic kidney disease] and diabetes?

 It’s extremely common, but patients don’t know they have it. If the caregiver doesn’t inform the patient, the patient feels fine even though they could have stage IIIB chronic kidney disease with a GFR [glomerular filtration rate] of 35 mL/min and urine microalbumin that’s high, and they have no idea that they have kidney disease. When patients need a statin, they may choose not to take it, but they know they have a lipid problem. If someone has diabetes, they may choose not to treat it, but they know they have diabetes. But in terms of chronic kidney disease, they don’t know it unless they have a nephrologist or are heading toward dialysis. That’s pretty sad, because we have terrific drugs that could help, besides lifestyle, not taking an NSAID [nonsteroidal anti-inflammatory drug], keeping good blood pressure management, and giving the RAS blocker. We have a lot of drugs beyond RAS blocker that may benefit their kidneys, and unfortunately the patients don’t know it. It’s up to the caregiver to inform them about it. It’s very common.

Dr Vaduganathan, when you talk about this and what you see, I would love to get the cardio-renal. There’s a huge implication in access. How should we be looking at this, and what’s the interplay as we talk about CKD, CV [cardiovascular] disease, and diabetes?

 It’s a similar intersection that’s large and under-recognized. If routinely screened with not just eGFR but also UACR [urine albumin-to-creatinine ratio] measurements, urine albumin and creatinine measurements, the overlap is likely to be even more substantial between heart failure, chronic kidney disease, and diabetes. In fact, recent series of hospitalized patients with heart failure suggest that over 60% have some degree of chronic kidney disease. Unfortunately, the heart and kidney have been considered enemies for a long time in terms of therapeutics. In many cases, patients who are at that intersection face the highest risks for near-term mortality and clinical events, yet are treated with the least amount of medical therapy. There’s this unfortunate risk-treatment paradox where high-risk patients are undertreated. That needs to be corrected. It’s fortunate that we now have therapies that target the intersection that may simultaneously benefit the heart and kidneys and don’t necessarily work against one another.

Absolutely. This is another space in which we haven’t had innovation in a really long time.

Dhiren Patel, PharmD, CECES, BC-ADM, Robert Busch, MD, and Muthiah Vadugananthan, MD, MPH, provide an overview of the prevalence of renal impairment in patients with diabetes.

Overview of Diabetes and Renal Impairment

Patrick Campbell is the senior editor of Endocrinology Network, as well as its sister publication Practical Cardiology. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. In his free time, he enjoys traveling, sports, and exploring the great outdoors. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

New research from an international team of investigators details the apparent increase in risk of psychiatric disorders, including behavioral and developmental disorders, among children born to women with diabetes.

An analysis including data from more than 2.4 million births within Denmark from 1978-2016, results of the study indicate children born to mothers with 

 during pregnancy had a 15% greater risk of receiving a diagnosis of a psychiatric disorder during their first 40 years of life compared to offspring born to mothers without a diabetes diagnosis during pregnancy.

“Our study shows a pattern in which prenatal exposure to maternal diabetes diagnosed during pregnancy was associated with increased risks for several psychiatric disorders in the first 4 decades of life,” wrote investigators. “Children born to mothers with any diabetes diagnosis during pregnancy had increased risks of any psychiatric disorder, schizophrenia, anxiety disorders, intellectual disabilities, developmental disorders, and behavioral disorders.”

In the wake of studies suggesting maternal diabetes was associated with increased risk of ADHD in offspring, the current study was conducted by a team of 6 investigators representing institutions in Asia, Europe, and North America to further investigate a potential association with the full-spectrum psychiatric disorders with maternal diabetes. To do so, investigators designed aa population-based cohort study leveraging data from multiple nationwide Danish health registries, which allowed them to identify a population of 2,413,335 live births occurring from 1978-2016 for inclusion in their analyses.

Investigators included 10 types of psychiatric disorders as their outcomes of interest. These were defined as: any psychiatric disorder, substance use disorders, schizophrenia, mood disorders, anxiety disorders, eating disorders, personality disorders, intellectual disorders, developmental disorders, and behavioral disorders. The exposure of interest was defined as any maternal diabetes diagnosis during pregnancy, which was further stratified according to the 3 subtypes of interest: pregestational type 1 diabetes, pregestational type 2 diabetes, and gestational diabetes.

Investigators assessed hazard ratios using Cox proportional hazards regression models with adjustment for multiple covariates, including maternal and paternal history of any psychiatric disorder, offspring sex, calendar period of birth, singleton status, and various maternal characteristics during pregnancy. Of note, sibship design and competing risk analyses were also included as part of the study.

In total, 56,206 individuals were born to mothers with maternal diabetes. This concluded 22,614 exposed to pregestational type 1 diabetes, 6713 exposed to pregestational type 2 diabetes, and 26,879 exposed to gestational diabetes. The 2,413,335-person study cohort included 1,239,148 (51.3%) men, had a median age of 19 (IQR, 5.8-20.8) years, and had an age range of 1-39 years. From the study cohort, investigators obtained a total of 412,662,622 million person-years of follow-up. During the follow-up period, 151,208 offspring received a diagnosis of a psychiatric disorder.

Upon analysis, results suggested offspring born to mothers with any diabetes diagnosis were at an increased risk of any psychiatric disorder (HR, 1.15; 95% CI, 1.10-1.20), schizophrenia (HR, 1.55; 95% CI, 1.15-2.08), anxiety disorders (HR, 1.22; 95% CI, 1.09-1.36), intellectual disabilities (HR, 1.29; 95% CI, 1.11-1.50), developmental disorders (HR, 1.16; 95% CI, 1.03-1.30), and behavioral disorders (HR, 1.17; 95% CI, 1.08-1.27) compared to offspring born to mothers without a diabetes diagnosis.

Investigators pointed out no associations of any maternal diabetes diagnosis were observed for risk of substance use disorders (HR, 0.99; 95% CI, 0.91-1.08), mood disorders (HR, 1.12; 95% CI, 0.90-1.39), eating disorders (HR, 1.21; 95% CI, 0.98-1.50), and personality disorders (HR, 1.09; 95% CI, 0.71-1.65). The sibship analysis indicated the association between maternal diabetes during pregnancy and any psychiatric disorder was attenuated but remained positive for exposure to pregestational type 1 diabetes and type 2 diabetes, with a more robust association of type 2 diabetes than was observed in the primary analysis.

“These findings suggest that careful clinical management of maternal diabetes during pregnancy is needed. Overall, our findings signal the importance of effective strategies for preventing, screening, and treating diabetes among women of fertile age for women’s health and children’s mental health,” investigators added.

Associations of Maternal Diabetes During Pregnancy With Psychiatric Disorders in Offspring During the First 4 Decades of Life in a Population-Based Danish Birth Cohort

Articles

An analysis of more than 2.4 million offspring in Denmark suggests children with exposure to maternal diabetes during pregnancy were at a 15% greater risk of developing a psychiatric disorder in the first 40 years of life. 

Exposure to Maternal Diabetes Could Increase Risk of Psychiatric Disorders in Offspring

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP:

 We’ve talked about insulin pens, insulin pumps, and a couple of different ways insulin can be delivered. However, continuous glucose monitors [CGMs] have revolutionized the field, and we’ve seen quite a bit of uptake not only from primary care providers but also from patients. I know this is something that comes up a lot in conversations, especially with some of my patients, where they tend to bring in a magazine clipping and say, “Hey, I want to go on this,” or they’ve seen a commercial that says, “I don’t want to check my blood sugars anymore.” Let’s talk about some of these challenges of self-monitoring blood glucose and the stories that you’re hearing from your patients. Also, how do you think the use of CGMs can help our patients with type 1 diabetes? I don’t want to discount the impact of this technology in that cohort, but a lot of it has been available to them early and its slowly making its way to our patients with type 2 diabetes as well. Dr Busch, you’ve seen that progression from when you were doing the urine [tests], but let’s pick up from the self-monitoring to the CGM technology.

That also has been a major game changer. The dietary compliance…“Please eat this, not that,” and the patient sees what they think is the same caloric load but very different glycemic excursions. The great part is you can download it in front of the patient and tell them, “This is your conscience. We can spy on you.” Not only can we check what meds they fill from [other providers], but [we can also say], “These are your readings. What happened this day?” Also, for the patient that tells me they are adjusting their basal between the 90 to 110 range, I can see their average is 130 and they have no lows in between. To be able to look at that with the patient there is incredible.

The major problem we have is the coverage because, in general, for type 2 [diabetics], at least in New York, they have to be testing 3 or 4 times a day and taking 4 doses of insulin a day. You almost want to give someone a prescription for Humalog so they can be testing or taking insulin 4 times a day, just so they could afford the CGM. Sometimes CGM is covered on plans, but other people are willing to pay out of pocket to do it.

Putting the Freestyle Libre [sensor] on is easy enough for the doctor to do—even I can do that and incorporate it in the visit. Then, the 2-week follow-up is with my educator, so they get to see the readings, take the [sensor] off for the first time and review it with the patient. It’s a real eye-opener.

Absolutely. The ease of use—you would think that technology is going to be complicated for patients to do. I deal with a geriatric population, and I tell them, “If you can put on a Band-Aid, you can put on a sensor”. It’s very easy. Dr Isaacs, can you talk about the role of CGM in patients with type 1 and type 2 [diabetes] and how it impacts disease management? Recently, CMS [Centers for Medicare and Medicaid Services] came down and there were a few wins there, so we know coverage seems to be pretty good.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES:

 Yes. Every person with type 1 diabetes should have access to CGM, there’s no question about it. Fortunately, we’ve seen coverage to be pretty good with people with type 1 diabetes. With type 2 diabetes or anyone who’s taking multiple injections of insulin, or even a basal insulin, there’s no question, [they should also have access to CGM]. Recently, the MOBILE study came out and showed the benefits in people with type 2 diabetes just taking basal insulin. More and more studies are showing benefits of CGM for people with type 2 diabetes, just like we see in the real world. Certainly, anyone that’s on any medication that could cause hypoglycemia, like a secretagogue or insulin, [should have access to CGM]. Guidelines are advocating for that, too. If you look at the ADA [American Diabetes Association] standards of care, [specifically concerning] their recommendations for CGM, they keep type 1 and type 2 diabetes together because they’re trying to say that people with diabetes benefit from CGM. It’s not separating out type 1 vs type 2. AACE [American Association of Clinical Endocrinology] also recently put out a guideline with technology and advocates for the type 2 population. You also mentioned CMS, and yes, that was a big win that they finally removed that 4-times finger stick.

 Which was kind of crazy because it was like people had to earn their right to CGM, and they would only get coverage for 3 finger sticks a day, but somehow they had to do 4 to earn their CGM. Hopefully we will continue to see coverage expand. Ideally, we would also get rid of the recommendations for having to be on all these injections, because people benefit from seeing their data, they learn in the moment.

Another thing, too, is the arrows. If someone checks their glucose before they go to bed and it’s 150, they may say, “OK, it’s safe to go to sleep.” But what if it’s 150, double arrows going down, and they’re dropping? A CGM can tell them that, or it can alert them in the middle of the night. With regular blood glucose monitoring, what are they going to do? They’re going to wake up in a sweat, if they do wake up. That’s scary, so, for sure, there are so many benefits to CGM.

 Yes, absolutely. As the body of evidence continues to grow, payer coverage is going to improve. Usually when CMS makes a change, a lot of folks point to it for good or for bad, but hopefully we’ll see a trickle-down effect.

A panel of experts discuss the impact of continuous glucose monitoring (CGM) on individualized patient care plans for patients with type 1 and type 2 diabetes.

Continuous Glucose Monitors in Type 1 and Type 2 Diabetes

 Diana, I know you do a lot of the nitty-gritty with the pumps. Dr Busch, you recommend it and you have a team that helps you make sure all the settings are correct on it. If each of you could talk to me about when you recommend an insulin pump, some of the benefits that you’ve seen, and how you work through that process as you see a patient. Dr Busch, we’ll start with you, then we’ll go to Dr Isaacs.

 Yes. [For example, say] my patient is on basal insulin and they tune up the basal to the fasting sugar. If they’re bottoming out before lunch or dinner and you see that’s not their rapid acting that they’re taking at mealtime, but the basal is too much during the day because of their activity, even though it was fine overnight—that’s someone who wants a variable basal and that’s where I’d recommend the pump. For someone who’s on multiple bolus doses and forgets to take their insulin with them to work, there’s the convenience of having the pump. Of course, you must get over that you’re wearing something, and some people don’t want to do that. But [this is] where you need a variable basal, [and to make sure] that your basal isn’t fixed to the morning reading. Also, if you’re bottoming out at lunch or dinner, or high pre-lunch to high pre-dinner and you need higher basal, how do you do that if you’re tuning up your basal to the fasting sugar?

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: 

Unfortunately,the reality is a lot of people with type 2 diabetes end up progressing to multiple daily injections. Of course, we try to optimize their SGLT-2 [sodium-glucose cotransporter-2] inhibitors and GLP-1 [glucagonlike peptide-1] agonists, but people are developing type 2 diabetes earlier in life. When you’ve had it for 40 years or 50 years, it’s not surprising that eventually insulin may be needed to achieve those glucose targets. For me, any person that is requiring multiple injections a day can be a candidate for insulin pump therapy. I find there’s a lot of misconceptions about a pump. People think, “Oh, that means you have the bad kind of diabetes,” or, “It must be serious,” and, “I failed at my diabetes management.” None of those things are true. It is just another method to deliver insulin, and often a much more convenient method. We’ve got pumps that have tubing. We also have pumps that don’t have tubing. It’s a convenient way to deliver insulin, so it’s something I share with my patients, and many people with type 2 diabetes are eligible through insurance coverage to be able to utilize [a] pump.

 Absolutely. Sometimes we paint everything with a broad stroke when we think about who those candidates are, but also when we talk about the category of insulin pumps. Dr Isaacs, while you have the mic, can you walk us through some of the options that are available from the more common manufacturers and how you filter through them for your patients?

Yes. We currently have 3 companies that have FDA-approved products, starting with Omnipod, which is a tubeless pump. A lot of people like that feature. It does hold a bit less insulin than the other 2 options, it holds 200 units instead of 300 [units], so that can sometimes be an issue for people who are on higher doses, but the tubeless feature makes it convenient. What’s exciting is that the Omnipod 5 is in the pipeline, which will have integration with Dexcom G6 to automate insulin delivery. We’re expecting that to become available in the second half of 2021.

We also have Medtronic. With Medtronic, the 630G is FDA approved for type 2 diabetes and that does integrate with their Medtronic Guardian Sensor to be able to suspend insulin delivery if someone is predicted to go below their low threshold. We also have other hybrid closed loop pump options with Medtronic, the 670G and the 770G, and those are FDA approved for type 1 diabetes. However, we know many times, in the real world, these are used off-label in people with type 2 diabetes that still experience a lot of benefit. And what’s in the pipeline for Medtronic is the 780G, which is approved in Europe and is a more sophisticated algorithm. It’s going to have an updated sensor, the Guardian 4, which will be more efficient and not have all those calibration requirements, so that’s exciting.

The final player we have is Tandem. The Tandem [t:slim] X2 [insulin pump] integrates with Dexcom G6. There is Basal-IQ [technology] where insulin is suspended if it’s predicted to go below 80, and then Control-IQ [technology], which is a hybrid closed loop that regulates insulin delivery and gives automatic correction doses every hour as needed to achieve the glucose targets. This is an exciting area and it’s continuing to rapidly evolve, but those are our current options and things that I like to share and go through with my patients.

 That’s excellent. Dr Busch, Diana just did a fabulous job of [describing] what our options are. When you step back and look at the big picture as we talk about automated insulin delivery and some other things, what excites you the most? What’s possible here for your patients as we think about this connectivity? Yes, you’ve been using insulin pumps for quite some time, but you’re now starting to see some of these integrations and interconnectivity that Diana mentioned. How does that affect the care that you provide?

 It’s customizing the care so the patient can own their diabetes. I know Diana and others are doing basal bolus pumps and connective pumps—that’s the term they tend to use—and I like that you can customize it or do precision diabetes management. I’m spoiled, so I get to work with someone like Diana, but she knows all that stuff while I’m busy with the cardiovascular outcome studies, the renal outcome studies, and that kind of stuff. I’m doing the rest of their diabetes, but my pump specialist keeps track of all those options, and we share the patients. I might see the patients every 6 months, she sees the patients every 6 months, so they’re being seen every 3 months, but they have the expertise of the pump [specialist] who knows all that [information], and then I’m doing their lipids, their blood pressure, and [handling] the other noninsulin drugs on top of what they’re on. It works out.

 We’re all fortunate to be in multidisciplinary practices where we have resources and we can share some of the work because it’s not easy. I always say it takes a village to take care of a patient with diabetes, so we’re all fortunate that we have a lot of different folks that can help on the care team.

Robert Busch, MD, and Diana Issacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, provide insight into the use of insulin pumps in type 2 diabetes and describe currently available smart pumps. 

Smart Insulin Pumps in T2DM

 Insulin delivery through the pen is probably the most common. Then, we have different delivery mechanisms, such as patch pumps, vials and syringes, and we also have it through insulin pumps, which we’re going to dive deeper into later. However, the more exciting ones that I find of interest are connected insulin pens and smart pens. Diana, can you talk about what you see in the landscape around connected insulin pens, your experience with the ones that we do have, and what excites you regarding the future products that we’re hearing about but aren’t quite here yet?

 Yes. The reality is most people using insulin right now are using insulin pens for vials. In terms of those using insulin pens, most of them are using that kind of standard, what you could even call a legacy insulin pen, something that dials an accurate dose but doesn’t help with calculations or record the dose. When you ask your patient, “How much did you take 2 days ago?” they don’t remember, and you don’t have any log of it. That’s where we now have the smart pens, and this is an area that is going to continue to grow. Like you mentioned, there’s more and more companies that are developing these products. However, this is incredible because it helps people to calculate how much insulin to take. We know that’s hard for people to remember, especially if they have an insulin-to-carbohydrate ratio. Or if they don’t have that, even if we give them a correction factor to add if their glucose is high, that is still hard to remember. Thus, it helps with those calculations, but it also helps the health care team. You know what your patient is taking, so [now] you can better adjust to be able to help them to achieve their glucose targets.

 I couldn’t agree more. Dr Busch, I know you have some experience as well and are aware of some of the other ones that are coming between some of the pens and attachments. You’re obviously visualizing a lot of the data that’s currently coming from the continuous glucose monitors [CGMs]. How do you see the connected smart pens? Having that additional data set, how does that affect your day-to-day, and how do you plan on incorporating that into your practice?

 It will be great because of all the other drugs that we have with GLP [glucagonlike peptide] and SGLT-2 [sodium-glucose cotransporter-2 inhibitor]. Not everyone—type 2 diabetics specifically—is on basal bolus therapy because we have so many other good drugs available. The thing I’m excited about is to have the weekly insulin out in the future. Should that get approved, that will be neat. The doses initially scare people because you’re on 7 times the dose, and then there’s a loading dose if you’re transitioning. However, having the smart pens would be a tremendous addition to what we’re having. It’s like a compromise between that and the pump.

 That’s a good point because even though pumps are an option, not everyone wants to be connected to a pump, or the cost is sometimes a barrier, too.

Experts in diabetes discuss recent advances in insulin pen technology, including connected and smart pens, and their impact on diabetes care.

Advances in Insulin Pen Technology

program titled “Pillars of Diabetes Care Technology.” I am Dr Dhiren Patel, adjunct associate professor of pharmacy practice at the Massachusetts College of Pharmacy [and Health Sciences] and an endocrine clinical pharmacy specialist. Joining me in this discussion today is: Dr Robert Busch, director of clinical research and apracticing endocrinologist at the Albany Medical College [Faculty Practice];and Dr Diana Isaacs, a clinical pharmacy specialist and the CGM [continuous glucose monitoring] program coordinator at the Cleveland Clinic Diabetes Center. Thank you both for joining me for this program.

 I want to start with talking about diabetes and the advancement that we’ve seen over the past decade, maybe even less than that—the last 5 years. Diabetes has grown leaps and bounds, not only when we think about it from a pharmacotherapy standpoint, but also the technology that’s available to us as ATPs [assistive technology specialists] and our patients. When we think about our 3 pillars of diabetes technology, the 3 buckets that I categorize them into are: Continuous glucose monitors [CGMs], insulin pumps, and now we have connected insulin and smart pens that are available. I want to quickly go around and get your reactions on how you see this diabetes landscape, especially since you both have had a front row seat to this changing paradigm. Any initial thoughts or reactions on how you see these 3 pillars, and a look back at history and where we are now? Dr Busch, I’ll start with you.

 When I started, people were still doing urine dipsticks, and we know how crude that was. At that time, sugar in the urine was bad. Now, with SGLT-2 [sodium-glucose cotransporter-2 inhibitor] therapy, we know sugar in the urine is good. To go from that, to having finger sticks where you had to cut the strips in quarters or eighths because they were expensive, match it calorimetrically, then to finally have a meter, and now to have CGM—it’s incredible. Just as the meds have advanced from sulfonylurea to the tantalizing array of drugs we have now, for the technology to advance like this—particularly the monitoring and the pumps—is incredible.

 Yes, I have to agree. To think people were checking their urine, and now we’ve got continuous glucose monitors that make it much easier to monitor glucose. Even with insulin pumps—when you think of the first pump, it was the size of a huge backpack, and now we have these small, discreet devices. We’re coming a long way and it’s continuing to evolve quickly.

 Yes, I agree. There’s a lot of technology available. We’ve come a long way to make the lives of our patients as easy as possible and for them [to] not [have] to think about their condition all the time. We’re going to be talking about a lot of this technology today—and we’ll also talk about some of the clinical outcomes—but all of the software metrics, the quality of life, and other things that are going to significantly help our patients from a patient satisfaction perspective will go a long way.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP; Robert Busch, MD; and Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, provide an overview of the pillars of technology utilized in diabetes care: Continuous glucose monitors (CGMs), smart insulin pumps, and connected insulin pens.

Role of Technology in Diabetes Care 

Dr Busch, I’d love to hear a real-life example of 1 of your patients. We have a 78-year-old gentleman who has a long-standing history of diabetes, high blood pressure, and dyslipidemia. Could you walk us through how you approached this patient’s CKD [chronic kidney disease] and what you did for him?

 This gentleman was referred to us. He had diabetes, hypertension, and hyperlipidemia. He was on a statin. His LDL was at goal. His triglycerides were not high, and he was on a maximal-dose RAS blocker with quinapril. Often, patients who are referred in are on metformin and DPP4. He was on sitagliptin-metformin combination. His GFR [glomerular filtration rate] was in the 50s mL/min, and he had urine microalbumin in the 200s mg/dL.

He had stage IIIA chronic kidney disease. Previously he was on a RAS blocker. It was recommended, “Don’t take an NSAID or a COX2. If you go to a hospital, ask not to get x-ray dye if you could avoid x-ray dye, and don’t do any nephrotoxic drugs. Don’t take any over-the-counter drugs other than Tylenol. No Aleve, Motrin, or Advil.” We go through that every visit with the patient. There wasn’t much more you could do until recently, seeing the SGLT2 data that are out now. His A1C [glycated hemoglobin] was low 7%. We could say, “He’s 78-years-old, so low 7% isn’t so bad,” but we wanted to do better.

The goal when any of us walks in the exam room is, “What can I do better than the time before?” We added dapagliflozin 10 mg after seeing the results of Dapa-CKD. We also upgraded his DPP4 to a GLP1 for the weight and cardiovascular [CV] benefits. Dulaglutide has the primary prevention indication. This gentleman didn’t have previously known ASCVD [atherosclerotic cardiovascular disease], or he probably has some clinical disease. Instead of being on sitagliptin-metformin, he’s on GLP1 and metformin and dapagliflozin. The dapagliflozin specifically benefits the glucose as well, although the higher the GFR, the more glycosuria you would have. As we teach our students, if the kidney doesn’t see it, the kidney doesn’t pee it. You have to filter glucose.

 You’re giving the dapagliflozin. Even if the GFR were 30-something mL/min, you’re still giving the dapagliflozin to prevent worsening kidney disease, but there it wouldn’t benefit the sugar that much. We upgraded his DPP4 to GLP1, which has its glycemic benefit, and added the dapagliflozin for renal protection. Because we’re in the Northeast, instead of the Acela train to dialysis, hopefully we’re delaying that train to dialysis and we’re flattening the curve.

That’s a really good point on the eGFR [estimated GFR]. I remind our trainees the same thing. It’s not like a light switch that’s working at 45 mL/min but not at 44 mL/min. There’s a rate of diminishing return. You also need to recognize that it’s not always being looked at from the glycemic lens. We have a QI [quality improvement] project going on from renal in which everyone is getting dose maxed out on an ACE or an ARB. They’re looking at it from some of the other pleiotropic effects. We also know they’re not dose-dependent CV benefits or renal benefits. That’s a great real-life use case regarding the most recent data from Dapa-CKD.

As we close out this segment, I’d love it if both of you could share some closing remarks. We talked a little about diabetes as well as patients who don’t have diabetes and what you see happening in the next few years as more options become available. Do you have any parting comments regarding cardiovascular disease, CV risk, or some of the renal implications we talked about? We’ll start with you, Dr Vaduganathan.

 I have 2 comments. One is that I thought Dr Busch nicely framed that patients are acutely aware of their kidney function and especially their near-term risk of dialysis. That’s an event they ask about and want to avoid. Patient activation is a really important strategy to potentially overcome therapeutic inertia in these circumstances. Making patients aware that new strategies are available to delay the need for dialysis is an important message to the community.

The second is from a heart failure lens. SGLT2 inhibitors form 1 of 4 pillars of heart failure care. Uniquely, though, it’s 1 of the only, if not 1 of 2, therapies that actually slow kidney progression in heart failure. While earlier therapies like ACE inhibitors and ARBs in the context of patients with heart failure may have even accelerated kidney decline, in this case, SGLT2 inhibitors—for the first time—have been shown to definitively delay clinical events, including progression to dialysis. That’s another motivating feature and benefit seen even among high-risk patients with established heart failure.

I absolutely agree. Those were some relevant points. When you have a patient who’s motivated, the possibilities are endless. We’ve all had those patients who come in and want something or that intrinsic motivation is a big piece. Dr Busch?

 You almost have to think to yourself, “Why shouldn’t I give an SGLT2? Where’s your ACE or ARB? Where’s your statin? Where’s your SGLT2? Look at all the benefits. Prove to me you don’t need the SGLT2 just like the statin and the RAS blocker. If we get to that, we’ll do more benefit than harm. You’re not going to give it to someone who has 6 yeast infections and is on an antibiotic. You’re not going to sneak it into a man with BPH [benign prostatic hyperplasia] who’s urinating every hour and say, “Now you can urinate every half-hour.” But you could sneak it in and give it every other day in the beginning. Try to get it on board and be comfortable with the safety profile for those who haven’t used it. It’s a terrific drug and has all those benefits we talked about.

Excellent. Thank you both for sharing this valuable information. We hope you found it very valuable in how you may think about implementing this in your practices. Thank you all for watching this 

A case study for a patient who required additional SGLT-2 inhibitors to help reduce progression of renal disease is presented, and Drs Robert Busch, Dhiren Patel, and Muthiah Vadugananthan share their final thoughts on renal protective agents.

Continuous Glucose Monitors in Type 1 and Type 2 Diabetes

Smart Insulin Pumps in T2DM

Advances in Insulin Pen Technology

Role of Technology in Diabetes Care

Case Study: Reducing Renal Progression With SGLT-2 Inhibitors