Conversations in Diabetes

Conversations in Diabetes provides an in-depth look at insulin management and treatment for patients with uncontrolled diabetes. Check in frequently for exclusive video interviews, Q&A’s and expert commentary on key issues facing clinicians today.

Patients With Diabetes Have Worse COVID-19 Outcomes

The COVID-19 pandemic has forced providers across various specialties to examine how the deadly virus impacts their patients. A recent study looked at whether patients with diabetes had worse outcomes and whether interventions could help improve their odds of survival. 

The authors used records of patients from VA national health records and found that patients with diabetes had a greater risk of adverse outcomes whether they used insulin therapy or not compared to those who did not have diabetes. 

Pandora Lucrezia “Luke” Wander, MD, MS, FACP, assistant professor of medicine and adjunct professor of epidemiology at the University of Washington, and an affiliate faculty member at the UW Center for Excellence in Maternal and Child Health, noted in an interview with MD /alert that while the patients they examined were all veterans, the results were likely still applicable to the general population as well. 

How was the study conducted?

We wanted to describe the magnitude of the association between diabetes and bad outcomes after COVID-19 and look at risk factors and mediators of the relationship using a large national cohort.

We used information from VA national health care records dating from January 2000. We found every individual in the system with a positive nasal swab for SARS-CoV-2 between March and July of 2020. Then we defined diabetes using laboratory values, medications, and diagnosis codes. We created statistical models of the association between diabetes and adverse outcomes (hospitalization, ICU admission, or death) within 30 days of COVID-19 diagnosis and with death over 3-4 months of follow-up. Then, among individuals with diabetes, we looked at factors that were associated with higher risk of these outcomes. Last, we looked at whether cardiovascular-disease related factors (including history of cardiovascular disease, heart failure, or chronic kidney disease; and use of some cardiovascular medications) played a role in the development of these COVID adverse outcomes.

What were your findings?

Diabetes with and without insulin use was strongly associated with greater risk of all the adverse outcomes we looked at compared to no diabetes. For example, people with diabetes who use insulin have a 63% greater risk of dying in the 30 days after they are diagnosed with COVID-19 compared to people without diabetes. In people with diabetes, prior use of some medications (like sulfonylureas and insulin) were linked to more frequent adverse outcomes, while prior use of statins was associated with lower risk of dying after COVID-19. Cardiovascular disease-related factors mediated only a small amount of the associations between diabetes and outcomes (less than 20% of the association in the case of every mediator we looked at).

What do these findings mean for patient care?

Doctors and other practitioners should counsel people with diabetes about this increased risk. We should be encouraging every eligible person to receive a COVID vaccination. Our results argue this is especially true for people with diabetes. The information in our study can be used to support this discussion with patients.

Were there surprises in your findings?

We were surprised that cardiovascular disease-related factors did not mediate a larger proportion of the hospitalization, ICU admissions, and death that we estimated was due to diabetes. This means that we need to look more closely at the role of other factors, such as hyperglycemia, altered inflammatory responses, and increased thrombotic activity, to figure out what is driving the higher risk of bad outcomes after COVID-19 in people with diabetes.

Do you have any sense if the results would have been different for the civilian population compared to veterans?

Quantitatively, the magnitude of many of the associations that we reported in our study are similar to results from smaller studies and research in other countries that was not limited to Veterans. Because of this, we are confident that the findings are generalizable to populations that are not made up exclusively of Veterans. 

What can be learned from this to help with overall diabetes care?

An ounce of prevention is worth a pound of cure. People with diabetes should do what they can to keep from getting COVID. This includes getting vaccinated as soon as they can.

What is the future of this research?

The relationship between diabetes and COVID may be bidirectional, with diabetes contributing to adverse outcomes after COVID and SARS-CoV-2 leading to worsening cardiovascular and metabolic disease. In our future work, we hope to learn more about the natural history of diabetes after COVID-19. Also, based on the findings in this analysis, we would like to learn more about the role of statins in mortality after COVID-19.


Video: USPSTF Issues New Recommendations to Lower Age for Type 2 Diabetes Screening

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The US Preventive Services Task Force published a new recommendation sheet for the screening of diabetes and prediabetes, lowering the recommended screening age from 40 to 35 for patients who are overweight or obese.  

Edward Gregg, PhD, a professor of epidemiology and biostatistics at Imperial College in London, who wrote a related editorial published alongside the recommendations in JAMA, spoke with MD /alert about the update. 

The new recommendations allow providers to prioritize patients most in need of intervention, Gregg said. While medications available have helped lower the mortality rate of diabetes drastically, more work is needed to address potential complications that can develop during the course of this chronic condition. 


What updates have been made to the USPSTF guidelines for screening for diabetes and prediabetes? 

On the surface, the update appears minor. It’s basically similar to the prior recommendations that people who are 35, well, in this case people 35 years to 70 should be tested for diabetes. Or should be tested for diabetes or prediabetes so that interventions can be initiated to prevent well, diabetes, or the complications and morbidity that follows. This recommendation changes the age. Whereas the prior recommendation was that people aged 40 to 70 be screened, this suggests that it should be started at age 35.   

I think what's important about this update though, is the broader context under which it's occurring, and that is that we're seeing that after a prior decade of good improvement in risk factor management in people with diabetes and actually some reduction in diabetes incidence we're seeing now that prevalence of diabetes is still persistently high and people with diabetes are not meeting their risk factor targets that could actually help them to reduce their risk of complication. 


Why are these updates important? 

I think it’s about helping providers to prioritize. Providers have a tough job these days with all of the potential options to prevent chronic conditions and to maintain good health. And so, what the United States Preventive Services Task Force is doing here really is helping providers to prioritize. And what they’re really saying here, in my view, I would not, I’m essentially an observer and a review of this work as well, is that we really should take the long view in that diabetes is a major public health problem. When it occurs, it affects people for years with enormous impact. And so, it requires a multifaceted approach. And what this is saying is that screening itself alone will not solve the problem. But it is a key piece. It's the starting point for initiating treatment and for prevention that's going to have an impact over the long term.  


What are you hoping to achieve by identifying diabetes and prediabetes earlier? 

The interventions are different. So, when this screening is done and you're looking for people with diabetes, you're looking to initiate early action and then really taking a long view of initiating action over the long term to manage risk factors such as levels of hemoglobin A1C or glycemic levels, levels of blood pressure and lipids that are going to by managing those and keeping them under control, you're going to reduce the risk of many long term complications. So that's the goal with identifying people with diabetes. 

The goal of identifying people with prediabetes is there's a lot of opportunity to prevent them from progressing to the need for medications, from progressing to having diabetes. And really, the justification for screening is that by screening, you identify both of those groups of people. And by acting early and efficiently, you can actually achieve both those objectives.  

Is the difference between 40 and 35 enough to make a considerable difference? Why not move the screening age younger? 

The problem with moving the age younger and younger is that you spend more and more time searching for people with diabetes amongst a group, wherein the levels are still, fortunately, pretty rare, right? So, by moving the age range down, what you’re doing is not actually adding that many people to the people that are going to be identified.  

However, this does reflect some of the unfortunate trends that we're seeing. And that is that first of all, young adults are developing type 2 diabetes at younger ages and in greater frequency than in the past. Secondly, when that happens, they typically do not have the levels of care and risk factor management that older adults do. And when people develop type 2 diabetes and in young adulthood, especially with the disease like diabetes that does its damage over time that’s a really bad prognosis for people if they are not able to act on it well. And so to develop diabetes in young adulthood means many, many years wherein it’s actually really important to manage risk factors such as those complications that can be prevented. But it's also an age group wherein the prevention of diabetes could be really important. 


What is it going to take to see consistent numbers in diabetes rates to level off or go down? 

It's probably going to require efforts at different levels. And we think of this as a problem that requires multi-tiered efforts wherein we want to identify people who are at very high risk because there's opportunities by giving them good attention, particularly to adopt healthy lifestyles in terms of diet, physical activity and maintaining healthy weight, we can actually prevent those people from progressing to diabetes. It's been shown that intensive lifestyle interventions can reduce incidence by 50%. And certainly at least delay the condition several years. And so that’s one of the things that we’re trying to do. 

But the other real complement to that given the diabetes risk factors really affect all of us, ultimately, they’re influenced by the communities that we live in, the foods that we eat that we have access to, how active we can be, and really our lifestyle over many years are things that we can do to change communities and the environment around us that can actually prevent our likelihood of moving into that condition or that state that we’ve been calling prediabetes. 


Is this a matter of younger people not getting the medical attention they need or not having access to the right care to catch the condition early? 

I think it’s a combination of things, you know. The challenges that young people have I think we all have in terms of our environment and communities around us not always being ideal for us to maintain healthy lifestyles. That that affects all of us. I think though that it's compounded with young adults because for a variety of reasons, the obesity epidemic affected youth in recent decades. And so, those youth are moving into young adulthood now and at starting levels of obesity that are higher. And that’s bringing their diabetes risk higher.  

But I think we also recognize that young adults may have additional challenges. There have particularly been difficulties being less access to insurance, for example. And it’s still more difficult for young adults to often get insurance that works for them to help them prevent chronic conditions. And then once they, even if they are insured, maintaining and having the contact with healthcare systems that are needed to help manage diabetes very well can be difficult for young adults who are trying to manage complex lives and maybe being with families, maybe in settings and without support around them. So, there’s a number of factors there.  


If someone is diagnosed with diabetes or prediabetes do we have enough treatments available that they could have access to get the help they need? 

For the most part, I think that’s the case. I mean, there's certainly more science that's needed both on the diabetes side and the prediabetes. People with diabetes still have an excess risk, an extra risk of a wide range of complications that we want to be much lower. And we need more science to help that. On the prevention side, or the prediabetes side we need more approaches I think that are evidence based to help us reduce that risk and lower the incidence of diabetes.  

But for many of these conditions, though, there actually has been a lot of success. And the bigger problem is not the development of new approaches but actually implementing what we know already works. And these issues, you know, the ways to manage hemoglobin A1C, or glycemic levels and cardiovascular risk factors, which make up such an impact on complications, it’s known how to do that in primary care. The difficulty often is it’s about the health systems and about how we can help people with diabetes from the point of their diagnosis to be well connected to their health care system, as such that they can see that management of those risk factors can be done efficiently, but need to be done over the course of a lifetime.  

One of the aspects about diabetes is that one of the positive or the pieces of good news is that survival is much greater now. Mortality rates among the population with diabetes have been decreasing consistently for decades now. And what this means is that once a person develops diabetes, they’re going to live a long time with that condition. But the problem is that long life with that condition doesn’t mean that they’re not going to have complications and problems from it. So, one of our goals within public health with people with diabetes is to have them live a long healthy life with diabetes rather than a long life with many, many other chronic conditions that follow.


Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Photo Credit: Getty


Video: Tirzepatide Improves Type 2 Diabetes Outcomes Better Than Semaglutide

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Tirzepatide is a novel GLP-1 and GIP receptor agonist, currently being investigated in phase 3 trials.  

Juan Pablo Frias, MD, Medical Director and Principal Investigator at the National Research Institute in California discussed the trial results with MD /alert, highlighting the strong efficacy and safety data.  

What was the idea behind this research? 

Tirzepatide is a unimolecular multifunctional agonist and it basically targets two different receptors, the GLP-1 receptor and the GIP receptor, which are both of the intricate hormones, whereas semaglutide is what’s called a GLP-1 receptor agonist. And this is the currently available GLP-1 receptor agonists like semaglutide and dulaglutide for example. So, tirzepatide is still investigational, and what we were looking at is to compare the GIP GLP-1 dual agonist to really the most potent GLP-1 receptor agonist, which is semaglutide.  


How was the study set up?  

It's a randomized control trial. It was open label, but it assessed the three doses of tirzepatide that are being assessed throughout the phase 3 program. So this is 5 mg once a week, 10 mg once a week and 15 mg once a week, versus semaglutide, the 1 mg semaglutide once a week.  

Again, it was a randomized trial: 4 arms, 3 tirzepatide arms and one semaglutide arm. And then patients were treated over a 40-week period and the primary endpoint was the change in hemoglobin A1C from baseline to week 40. Looking at the three tirzepatide doses versus semaglutide 1 mg dose. 


What were your findings? 

What we found in this study was that tirzepatide at all three doses, the 5 to 10, and the 15-mg dose was superior to semaglutide at 1 mg with respect to lowering of hemoglobin A1C. The proportion of patients achieving a hemoglobin A1C less than 7 less than or equal to 6.5% and less than 5.7%, or 5.6% I should say. And also superior with respect to weight reduction with very high proportion of participants achieving clinically relevant weight targets which would be greater than or equal to 5, 10, and 15% weight loss over the 40-week period.  

And I think a very important finding, I mean clearly, it's important to see what the overall or the absolute reduction in hemoglobin A1C is, but it's the percent of patients achieving hemoglobin A1C targets. And what we found not only in SURPASS 2, which was versus semaglutide, but in the other SURPASS trials that have completed, is very high proportion of patients, you know up to 90% or even more of patients achieving a target A1C of less than 7%. And I think very importantly and very consistent across these trials anywhere from 45 to up to 60+ percent of patients actually normalizing glucose and achieving hemoglobin A1C’s of less than 5.6%.  

And similarly with weight targets, I mean a very high proportion of patients achieving really weight reduction that has not been seen in patients with type 2 diabetes previously, with up to 40-45% of patients achieving greater than or equal to 15% on weight reduction with tirzepatide. 

I think very importantly if I could add, that’s looking at the efficacy endpoints, but with respect to safety and tolerability, very positive as well. In the earlier trials when we have reached the highest receptive doses very quickly, there was more of an issue with GI tolerability in the phase 2 studies. But with the titration and dose escalation algorithm that have been used in these phase 3 studies much better tolerability.  

And in fact, if you look at the tolerability of tirzepatide versus semaglutide for example, so a selective GLP-1 receptor agonist you get basically the same nature or the same type of adverse events, the primary one being gastrointestinal adverse events or nausea, vomiting, diarrhea. But much better tolerated in phase 3 compared to phase 2 with the new escalation algorithms that were used.  


How do you determine dosing for tirzepatide? 

As with the GLP-1 receptor agonist, you definitely have better tolerability of these drugs when you started with a lower dose and then dose escalate slowly. So, what was done in in all of the phase 3 tirzepatide trials is to initiate therapy with 2.5 mg once weekly. And this is a subcutaneous injection. And the dose was then escalated by 2.5 mg every four weeks. So, patients went from 2.5 mg for four weeks to 5 mg. So to get to the 5 mg dose that was studied, it took four weeks and to get to the 10 milligram dose it took 12 weeks that the patient went from 2.5mg for four weeks, then five, 7.5, and then 10, and then to get to the 15 mg dose it was actually 20 weeks or 2.5 mg increments every four weeks. So, in these studies, you know, was set the patients were randomized either to 5, 10, or 15 mg. And that was, you know, blinded to the investigator what doses the patient ended up on. But all three doses were very effective.  

I mean, as an example, in the SURPASS-2 study, which was recently published in the New England Journal versus semaglutide, even though the 5 mg dose, which was the lowest dose that was studied, was superior with respect to hemoglobin A1C reduction as well as weight reduction compared with semaglutide. So I imagine in clinical practice should tirzepatide get approved by FDA and become commercially available, we’ll just need to decide this in the clinic. You know, if a patient’s doing very well with the 5mg dose there may not be a need to escalate to the 10mg dose. And if patients are, you know, get escalated and they're having GI side effects at a higher dose, you know that's a patient that I would potentially deescalate or reduce the dose on. And I think it is important to point out that in, for example, the SURPASS-2 study we were not allowed as investigators to reduce the dose as we would in clinical practice if a patient did have issues with tolerability. 

Judging whether a dose is going to really be as successful, it’s going to be individualized, you know. If clearly, I mean, I’m treating diabetes here. So, one of my key endpoints is going to be improving hemoglobin A1C. So, generally, in practice we’ll individualize the target hemoglobin A1C depending on a number of different patient characteristics. But, you know, I think the key one would be is my patient achieving the A1C target that we’d like to get to.  

Some patients were more concerned about weight loss, so maybe they've achieved their A1C target, but we feel that we'd like them to lose more weight. So that may be another reason to escalate if I'm on a dose that's lower than the maximal dose. And certainly, tolerability plays a huge role in this as well. The patient might be achieving all these targets, but if they're not tolerating the medication well, I may want to reduce the dose. But primarily, you know, knowing whether to escalate, and whether I've sort of reached the maximum dose, those will primarily be based on hemoglobin A1c. So, glycemic control as well as body weight control. 


What role did previous metformin use have on your findings? 

So, these patients were all taking metformin. So, it was a study in patients on metformin monotherapy, so metformin therapy for at least three months. In this case they had a mean duration of diabetes of a little over 8 years. There was another study, this one called SURPASS-1. This study was recently published in The Lancet. And that looked at tirzepatide as a monotherapy. So, these were patients and were either drug naive or at some point had been on oral antidiabetic agents but were not on them for at least three months. So, this was looking at tirzepatide on top of diet and exercise therapy. And very consistent looking at that population compared to SURPASS-2.  

But most patients, I mean the recommendation today if we look at our guidelines is that you would initiate with metformin therapy or maybe metformin and SGLT 2 inhibitor for example, particularly in patients that have cardiovascular disease or a renal disease. So, this could be looked at tirzepatide as an add-on therapy as we consider GLP-1 receptor agonists today. But certainly, there are going to be situations where patients can’t tolerate metformin or have complications from metformin, for example. Or when we want to initiate combination therapy from the get go where incretin-based therapy like a GLP-1 receptor agonist may be appropriate as, you know, the first step in the therapy, or in combination with metformin from the beginning. So I think this is where tirzepatide could eventually fit in as well, either, you know, as a monotherapy, or as add-on therapy to pre-existing treatment in patients with type 2 diabetes. 


Could tirzepatide fill an unmet need in diabetes care?  

I think it addresses an unmet need. If we look at GLP-1 receptor agonist therapy today, you know, these agents are very potent, semaglutide, dulaglutide as well. There’s still patients that remain basically without achieving their optimal control. And, in fact, if we look at dulaglutide for example, there was recently a study and a new indication for higher doses. So going from 1.5 to 3 or 4.5 mg once weekly to address that same unmet need that some patients at 1.5mg do not achieve their target. And similarly, with semaglutide, the maximal dose is 1mg. But we recently presented data looking at 2mg, a higher dose of semaglutide for type 2 diabetes, again because of that unmet need that, you know, although in clinical trials up to 80% of patients with the 1mg semaglutide dose achieve an A1C of less than 7%, you’re still left with some people who are not achieving this target.  

So, I think this addresses the need. One of the needs for better glycemic control in many patients as well as this combination of really unsurpassed glycemic control with the weight reduction that's seen with this new agent, this dual agonist. And I think, you know, if you, if you look at these studies as well, it’s not only the A1C and body weight, but you're also seeing improvements in blood pressure, improvements in the lipid profile as well.  

And I think some very interesting if you look at the New England Journal paper, there's a composite endpoint that was predefined, and I thought it was very impressive and I think clinically relevant. It looked at the proportion of patients with tirzepatide that achieved a hemoglobin A1C of less than or equal to 6.5% and weight loss greater than or equal to 10%, and no significant hypoglycemia. So, sort of this triple composite endpoint. And with the 15 mg dose, this was reached by approximately 60% of the patients. And with semaglutide it was reached by 20%, so 1/5 of the patients, which is still pretty darn good. Because they’re just very sort of extreme targets if you will. So I think it is addressing the need for better control in some of our patients that are already treated, sort of, with the most potent antidiabetic agents. 


What can be done to help diabetes care overall going forward? Is it more medications? Better education? 

You know, I think I think it's all of the above and I would say you know, despite the fact that we've had significant advances, I think in pharmacotherapy, in diabetes related devices, in our knowledge about the importance of good glycemic control. You know in cardio renal protection, many patients are still not achieving their targets. I mean, we saw that recently in the latest latest data from CDC and you know, and Haynes and in the New England Journal of Medicine looking that despite all of this, you know as a population we're not achieving glycemic targets are not getting better with respect to achievement of glycemic targets. So I think a lot of this also has to do with education, physician education, patient education, and very importantly access to these medications. I mean, you know it's great to have these very powerful medications, but our patients need to have access to them. So I think it's having the more powerful and more efficacious medicines, but it also is education and actually having access to these medications if you're a patient. I mean, that's obviously critical to this as well. 


Disclosures: Frias reports research support, advisory board and consulting roles, and speakers bureau roles with Eli Lilly. Frias also reports additional pharmaceutical disclosures unrelated to the study. 


Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.


Video: Cardiologists Slow to Prescribe Cardioprotective Diabetes Medications

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Kunal Jha, MD, Preventive Cardiology Fellow and Rishav Adhikari, MD, Medical Student, both of Johns Hopkins School of Medicine, presented new data at the 2021 ACC Scientific Sessions showing that cardiologists have been slow to prescribe new diabetes agents despite their cardioprotective benefits.  

Drs Jha and Adhikari spoke with MD /alert about their findings and why cardiologists may be hesitant to adopt these new medications. 


What was the idea behind this research? 

Adhikari: There are two classes of drugs. SGLT2 inhibitors and GLP-1 receptor agonists. And these originally came out as blood glucose lowering drugs for patients with diabetes, patient detected diabetes. And by a somewhat fortunate accident we started getting data back that these drugs, when patients receive these drugs, that it mitigates their cardiovascular risks. And one of the major risks for patients with type 2 diabetes are heart risks, risk of heart disease and stroke.  

And so, they came out as diabetes drugs, but we're finding out that they may be more useful as cardiometabolic cardioprotective drugs. And so, what this study is looking at is, well, are cardiologists actively participating in prescribing these cardioprotective drugs?  


Can you discuss how you conducted your study? 

Jha: We did a cross sectional study here where we looked at the prescription pattern of in cardiologists and other providers over the last five years from 2015 to 2020. And we use the IQVIA, a national prescription audit database, which looks at like close to 90% of retail prescriptions, including both SGLT2s and GLP-1s. So, in last five years there was close to 12 million prescriptions to 124,000,000 prescription. And we were just looking at the what was the prescription pattern by each specialty, which molecule were preferred by the cardiologist versus other providers? And what was the factors that influenced their prescription patterns. So, I think Rishav did a great job in gathering all those data and then writing up this abstract for ACC. 


What were your findings? 

Adhikari: What we’re seeing is that basically a very small fraction of these prescriptions come from cardiologists. That the majority of the use of these drugs comes from primary care physicians, endocrinologists, physicians that traditionally treat diabetes, but not so much from cardiologists who might be managing cardiovascular risks.  

But on the bright side, use of these products by cardiologists is growing really quickly. It's grown. Monthly use for SGLT 2 inhibitors has gotten 12 times higher by cardiologists since six years ago since January 2015. And for GLP-1 receptor agonists it’s about four times higher than it was in January 2015. So, cardiologists are using more of these drugs, but still represent a very small fraction of total use.  


Did you find out why cardiologists are or are not prescribing these medications? 

Adhikari: No. that’s something that our study I think is unable to answer. People speculate about that question a lot and I think it’s a really important question that we need to answer because these drugs are underutilized, and cardiologists can definitely play a big role.  

I think some hypotheses we have that our data might suggest is that that these drugs might have been kind of pigeonholed because they came out as diabetes drugs before we found out that they were cardiovascular drugs as well, and so they’ve been kind of pigeonholed as diabetes drugs, and they have had trouble making it out of that realm.  

For the GLP-1 receptor agonists, they are drugs that most of those drugs require injections and cardiologists unlike primary care physicians and endocrinologists that that that prescribe a lot of insulin that requires injections and are used to counseling patients on injectable drugs, cardiologists may have less experience there.  

There are many other hypotheses. They are very expensive drugs compared to like a statin or a metformin, which is used by most, and should be used by most patients with type 2 diabetes. So, there's a whole host of, I think hypotheses for why uptake has been low. And by the way, not just among cardiologists. I think if you there are other studies besides ours that show that if you just look at the population of patients that should be on these drugs, it's definitely less than like 20% of the patients that should be on these drugs are actually on them.  


What can your research mean for patients and providers? 

Jha: They are different types of cardiology providers: some are ED physicians, some are interventional cardiologists, and there are general cardiologists as well. Some cardiologists practice at academic centers, other practice at private practice. So, the issue here is that a lot of providers, the clinicians, the cardiologists might not feel comfortable prescribing this medication because we have to titrate other antidiabetic medication which can lower the blood sugar level. And so the main thing is the comfort level. And the second thing is follow up with this patient.  

Imagine a cardiologist already has a busy practice. They have to start blood pressure medication. They have to start a statin and they have to start other medication as well. On top of that, if the cardiologist starts managing diabetes like, blood sugar level and that, it will be too much to ask from them. So that's the reason people will generally prefer to refer those patients to an endocrinologist, or like primary care doctor.  

So, I mean, a lot of people feel that it's not their responsibility to manage diabetes, especially for those high-risk patients. That could be one of the reasons we feel that cardiologists might not be prescribing enough, and that's the reason there is a clinical and therapeutic inertia in the management of such high-risk patients.  

Adhikari: I think some of the things that we can take away from our study is that there is quite a gap in, like cardiovascular management of patients with diabetes within cardiology, and that cardiologists seem to recognize that that gap exists, that that they may not be serving their patients with diabetes as well as they could based on the most recent data. And on top of that, I think that our study really provides some urgency to try and understand what are the reasons. More research into understanding what are the barriers for cardiologists becoming more involved in in this area. 


Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Video: Combo Therapy Effectively Improves Outcomes in T2D Diabetes Patients with CKD

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Frank Qian, MD, of the Department of Medicine at the Beth Israel Deaconess Medical Center and colleagues recently presented a study at the ACC 2021 Virtual Scientific Sessions that sought to determine if therapy renin-angiotensin-aldosterone system (RAAS) inhibition combined with other diabetes agents could improve outcomes. 

Dr Qian spoke with MD /alert about the result of their study and how they could impact clinical practice for patients with diabetes and kidney disease. 


Can you explain the purpose of your study? 

The general idea behind the study is we know that patients with type 2 diabetes and chronic kidney disease are at very high risk of kidney disease progression, meaning dying from complications of kidney disease, either from dialysis or from what we call renal death. But at the same time, we also know that these same patients have a very high cardiovascular risk. And actually, many of these patients will go on to develop cardiovascular disease and die from cardiovascular causes before they experience progression of their chronic kidney disease.  

So, the general idea was, you know, prior to I would say the past several years, the only therapy or pharmacological therapy that was known to prevent both kidney disease progression as well as cardiovascular disease in this population were inhibitors of the renin angiotensin system, specifically ACE inhibitors and angiotensin receptor blockers. 

But recently, just in the past several years, there’s been a multitude of trials looking at three different classes of pharmacological therapies. Specifically, mineralocorticoid receptor antagonists, and in this case, finerenone, as well as SGLT 2 inhibitors, in addition to GLP-1 receptor agonists. So that’s sort of the three classes of medications I looked at. The idea was to look at if we get a patient on all of these drugs, in addition to  whatever ACE inhibitor or angiotensin receptor blocker they might already be on, what is the clinical benefit we could derive from that? 


How did you conduct this study to determine the efficacy of combination therapy? 

There were a few steps. The first was to kind of systematically search for and identify these pivotal trials in which they enrolled patients with both Type 2 diabetes as well as chronic kidney disease in the three classes of medications I had mentioned before. Then deriving the risk estimates either from the reported trials or sometimes, we would have to contact the specific investigators, then combining them and doing a meta-analysis in which we synthesize the overall effect estimates for. 

We looked at several different clinical outcomes, including progression of kidney disease, end stage renal disease, cardiovascular outcomes including heart failure hospitalization and mortality outcomes as well, and using a method that's pretty well established in the field of epidemiology, which is called indirect comparison. So, we basically combine the effects of all these medications into the overall effect by assuming that we're comparing each one to a common comparator, in which case this is just the ACE inhibitor or ARB.  


Can you describe the study results? Did combination therapy improve patient cardiovascular outcomes? 

What we found out is that when we combine these three medication classes, we had a really substantial reduction in actually all of the outcomes who looked at. So, the largest benefit was for preventing the two renal endpoints as well as what we call renal composites. So, this is looking at sustained declines in EGFR or estimated glomerular filtration rate, as well as progression to dialysis or end stage renal disease more generally.  

The cardiovascular outcome that was reduced most significantly was heart failure hospitalization. But we also saw effects on reductions in major adverse cardiovascular events, which is a kind of a combination of cardiovascular death, myocardial infarction, and stroke, as well as cardiovascular death, as well as all cause mortality. 

So, all of these important outcomes that, you know, cardiologists and, you know, kidney specialists, as well as definitely the patients are really most concerned about. We found that if patients were to be treated with all of these therapies, then we can have a really substantial benefit for them in terms of reducing their risk.  


What impact do you think these findings could have on clinical care? 

I think many doctors in the in the field, particularly I would say cardiology and nephrology are probably aware of some of this data. But I think this is probably the most systematic analysis that's been done on this topic. And because a lot of these medications physicians might not know we could use them together, mainly because two of the classes are for glucose lowering.  

And there may still be some hesitation in the field about putting a patient on multiple glucose lowering medications, with the concern that, you know, could I be causing hypoglycemia? But this is one analysis we haven’t done yet. We are certainly planning to look at the safety outcomes, whether they might be still safe to combine. And from a preliminary investigation, it seems like these drugs can be combined safely. 


Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.

Video: Mobile App Interventions Could Help Diabetes Medication Adherence

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Antoinette M. Schoenthaler, EdD, Associate Professor, Department of Medicine at the NYU Grossman School of Medicine, and colleagues studied the impact of a mobile health intervention on diabetes medication adherence among Black patients with high-risk comorbidities.

Dr Schoenthaler discussed her team’s findings with MD /alert.

What was the goal behind this research?

Medication adherence is a very pervasive problem. And you know, despite decades of research, we still haven't quite been able to tackle this problem in a way that has shown good and sustainable outcomes. One of the problems is that there's not a one-size-fits-all model for medication adherence. We really need to be able to tailor our intervention strategies to the barriers that patients face in taking their medications, and that can be a multitude of things.

So, this came out of the idea that let's create a personalized approach that really kind of elicits what patients barriers to make change medication adherence are and then pair those barriers with intervention strategies that we know are effective to address those barriers.  

Can you discuss the inequities in diabetes care associated with race, and how your research focuses on race?

There’s great health inequities in diabetes and hypertension outcomes in the black population. And we also know that medication adherence tends to be poor in this population. So they’re a really high-need population.

How was this study conducted?

All of my work uses what we say is a user-centered approach in the sense that any intervention we build, particularly tailored or personalized intervention, includes feedback from the target group that we’re going to then work with. We started by doing interviews and focus groups with black patients who had hypertension and diabetes to really understand what their barriers to medication adherence were and what kind of strategies would help them improve their adherence.

We took that data and we then matched it with what we know in literature is also helpful and then we created the mHealth tool that used different strategies and built it into kind of an interactive web-based program. So, things like using storytelling, games, and other kinds of ways to get people to think about their medication adherence or taking their medications and then have to kind of overcome those barriers.

What were the most common barriers found in your research?

The big ones are always kind of motivation and attitude related. So, a lot of people just don’t believe they need the medication for the rest of their lives or just don’t trust the medications. And so most often they were paired with, like, patient vignettes, where a patient similar to them would tell a story about kind of that same belief and how they ended up maybe needing hospitalization or kind of the negative effects, and another is always cost related. That’s a big one.

Just the affordability of medications, particularly from multiple medications because you have multiple chronic diseases, costs come in. And so linking them to pharmacy, local pharmacy resources and national programs that can help offset the costs as well as empowering them to talk to their doctor about getting generics for their medications which are equally effective. And then forgetfulness. That always seems to be where, you know, busy lives and so it’s easy to forget and so coming up with strategies to help them remember, particularly medications. 

How successful was the program?

It was a small pilot, so I’m just going to kind of say that with the caveat. But we did show improvements in medication adherence and decreases in systolic blood pressure, about four and a half millimeters of mercury, which is, you know, pretty good, considering it was very small and only three months in time. But, you know, and overall, patients really liked it and they wanted it to be something that they could do in their waiting room that’s, that was like one of our biggest suggestions is, you know, I sit in the clinic waiting room doing nothing, would it be cool if I could play this game while I’m waiting. And then, you know, help me have a conversation with my doctor when I do see them to talk about the kind of things that came up in the game.

Would this be something prescribed by doctors? Available in the App Store?

You can go both ways. So, one is it could be a clinic waiting room program. So, I know in like my pediatric office for my kids they had me a tablet to fill out all kinds of information to check in and things like that. And this could be something that’s part of that kind of registration experience. Like, you’ve answered your questions, there’s common that we do screeners in the clinic waiting room like on depression, why not screen for medication and non-adherence as well?  And you’re kind of using that window of time where patients are just sitting anyway. It could also definitely be something that people find in an App store if they’re interested and, you know, doctors can also prescribe it. We’ve seen success with doctors prescribing things like increased physical activity. You know, why not taking your medication, given how big of a problem it is?

Were there surprises in your findings?

I think one of the things, you know, we were hoping that you know patients would say, you know, this is a great tool, you know, and it could be a standalone. But people still want that one-on-one person contact. So we were, you know, we’re hoping by including narration and vignettes and kind of giving it this personal touch that we could not eliminate the need for a health coach or, you know, paid personnel, but just kind of make this a substitute in some ways to help practices who may not be able to hire  health coaches or other types of services. But patients still really wanted that one-on-one contact of someone checking in on them.

Where does your research go from here?
My work to date has really now been about making this a much more sustainable approach. So, not just kind of a one-off research study where we’re testing it and then once, you know, the funding is done, the grant program is gone. But really, how do we integrate these things into care? Leveraging things like electronic health records or another dissemination stream could be the patient portal or patient, you know, chart that they see, and how do we kind of integrate these into care like you were just suggesting?


Any views expressed above are the author's own and do not necessarily reflect the views of MD /alert. This transcript was digitally generated and edited for clarity.