Coverage of the American Diabetes Association's 81st Scientific Sessions (ADA 2021)

ADA 2021

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 data from a phase 2 trial suggests licogliflozin, a dual SGLT1/2 inhibitor, could offer potential as a treatment option for 

While much of the attention paid to dual SGLT1/2 inhibitor agents has been given to 

sotagliflozin and its cardioprotective effects

, results from the phase 2 trial of licogliflozin suggest use of the agent could lead to improvements in hyperinsulinemia and androgenemia in women with PCOS.

“SGLT1/2 inhibition may represent a novel therapeutic option for patients with PCOS. Further studies with longer treatment duration considering milder PCOS phenotypes and clinical outcome parameters such as ovulation rate are warranted to elucidate the full potential of dual SGLT1/2 inhibition in PCOS,” wrote investigators.

With previous data indicating dual inhibition of SGLT1/2 could reduce hyperandrogenemia and hyperinsulinemia, but not trials examining SGLT1/2 inhibition in patients with PCOS, the Novartis Pharmaceuticals-led study was created with a randomized, placebo-controlled, double-blind, multicenter design to assess whether use of licogliflozin would impact androgens in women with PCOS. Conducted between October 4, 2017 and June 4, 2018 at sites in the US and Germany, enrolled 29 women and randomized them in a 1:1 ratio to licogliflozin 50 mg or placebo for 2 weeks. 

All patients included in the trial fulfilled Rotterdam criteria for phenotype A or B, were overweight or obese, and were considered insulin resistant. The primary endpoint of the study was the effect on geometric mean of serial free testosterone (FT) samples and parameters of insulin resistance, including total testosterone, androstendione (A4), DHEA, dehydroepiandrosteronsulfate (DHEAS), and SHBG.

Per study protocol, patients received oral doses of 50 mg licogliflozin or matching placebo 3 times per day for 14 days before meals. Study evaluations for safety or efficacy were performed on days 8, 15, and 22 of the trial.

The study population had a mean age of 27.6±5.3 years, a mean bodyweight of 105.2±18.7 kg, and a mean BMI of 38.1±6.3 kg/m2. Overall, 15 were randomized to licogliflozin and 15 were randomized to placebo. Investigators pointed out 9 subjects were excluded from analysis due to evidence of ovulation or missing baseline values, but noted baseline values were similar between the study arms.

Upon analysis, investigates observed no change in concentration of free testosterone based on use of licogliflozin. Licogliflozin was associated with a 19% reduction in A4 (TR

Additionally, results suggested hyperinsulinemia was reduced by 70% with use of licogliflozin ([TRLIK066:TRPCB(MAXI): 0.26; 90% CI, 0.20-0.34; 

 < .001]). Safety analyses indicated diarrhea and nausea occurred as common adverse events with use of licogliflozin.

“We present the first placebo-controlled, randomized trial with a dual SGLT1/2i in patients with PCOS showing a licogliflozin-mediated reduction in glucose, insulin as well as A4 and DHEAS concentrations after 2 weeks of treatment,” wrote investigators. 

Licogliflozin versus placebo in women with polycystic ovary syndrome (PCOS): a randomised, double-blind, phase 2 trial

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Data from a phase 2 study of women with overweight or obesity and polycystic ovary syndrome suggests use of licogliflozin was associated with significant reductions in hyperinsulinemia and androgenemia in this patient population.

Licogliflozin, a Dual SGLT1/2 Inhibitor, Shows Potential as Treatment for Polycystic Ovary Syndrome

The US Food and Drug Administration has approved the Senza System from Nevro Corp. for the treatment of chronic pain associated with painful diabetic neuropathy, according to a 

With approval, the 10 kHz high frequency spinal cord stimulation therapy, which Nevro will market as HFX

 , becomes the only spinal cord stimulation system approved by the FDA with a specific indication for painful diabetic neuropathy.

"Diabetic neuropathy is one of the most prevalent and debilitating, chronic complication of diabetes, and for years, PDN patients have struggled with a lack of effective treatment options when conventional medications fail or are not tolerated," said Frances Broyles, MD, Medical Director of Diabetes/Endocrinology and Nutrition at Swedish Health Services in Seattle, Washington. "The ability to now offer Nevro's proven 10 kHz Therapy, which may enable discontinuation of long-term drug therapy and eliminate unwanted drug side effects, is a welcome addition as a treatment option for my PDN patients dealing with this challenging condition. My personal practice experience with the Nevro 10 kHz Therapy was nothing short of life changing for the patient."

Approval of the therapy is based on the results of the SENZA-PDN trial, which demonstrated use of the system was associated with significant improvements in quality of life and substantial, sustained pain relief. A 216-person trial assessing use of the system versus standard medical management, 6- and 12-month results of SENZA-PDN were published in 

In the trial, 82% of patients randomized to standard medical management opted to crossover to HFX. At 12 months, results indicated patients using the system experienced clear, sustained benefits in regard to lower limb pain, pain interference with daily living, sleep quality, and activity. The statement from Nevro Corp. noted plans to publish the 12-month results in a peer-reviewed journal and also pointed out plans to continue the study out to 24 months.

"This FDA approval marks a capstone achievement that demonstrates the strength of our clinical data and provides a proven, new breakthrough SCS treatment option for PDN patients who are struggling with debilitating pain and who are unable to find relief with currently available pharmacologic options," said D. Keith Grossman, Chairman, Chief Executive Officer and President of Nevro. "We are thrilled that we can now begin commercial launch activities in the U.S. and believe this new indication will be an important driver of the long-term growth of our business for years to come."

For more on SENZA-PDN, check out our coverage of results from ADA 2021.

With approval announced on July 19, HFX becomes the only spinal cord stimulation therapy approved by the FDA with a specific indication for painful diabetic neuropathy.

FDA Approves Spinal Cord Stimulation Therapy for Painful Diabetic Neuropathy

The US Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted against recommending approval of roxadustat for the treatment of anemia in adult patients with 

, regardless of whether or not they were on dialysis.

The committee voted 13-1 against the approval for treatment of chronic kidney disease in patients not on dialysis (NDD) and 12-2 against the approval for patients on dialysis (DD), citing concerns over an increased risk for thrombotic events and other major cardiovascular adverse events.

“New solutions are needed for the six million people in the US affected by anemia of chronic kidney disease. Although we are disappointed by today’s outcome, we will continue to work closely with our partner FibroGen and the FDA to determine the path forward for roxadustat,” said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, in a 

, who is developing the agent in collaboration with FibroGen Inc and Astellas Pharma Inc.

“While we are disappointed with today's outcome,” said Enrique Conterno, Chief Executive Officer of FibroGen,

. “We believe the scientific evidence supports roxadustat approval in the U.S. and will work with the FDA as it completes its review of the New Drug Application for roxadustat.”

An oral, small molecule, hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, roxadustat was the first HIF-PH inhibitor to be accepted by the FDA for review in treatment of anemia in patients with CKD. Evaluated in a phase 3 program including more than 8000 patients and half a dozen trials, data behind roxadustat has warranted approval in other countries such as China, Japan, Chile, and South Korea for treatment of anemia in CKD in NDD and DD patients. The agent is also under final regulatory review with the European Medicines Agency.

“The sponsor has done its clinical trials with a very specific strategy but now would like approval for a strategy which has been developed only as a simulation. If they really want people to use the new strategy in clinical practice, they really do need to test it and show its efficacy and safety,” said Milton Packer, MD, FDA CRDAC committee member and cardiologist at Baylor Medical Center, after voting against recommending approval for treatment of anemia due to CKD in NDD.

The subject of a July 15 meeting, the FDA's Cardiovascular and Renal Drugs Advisory Committee voted 13-1 and 12-2 against recommending approval of roxadustat for treatment of anemia in adult patients with chronic kidney disease not on dialysis and on dialysis, respectively.

FDA Panel Votes Against Roxadustat, Cites Risk of Thrombotic Events

A study funded by the Physicians Committee for Responsible Medicine suggests implanting a plant-based diet could help lower the impact of menopausal symptoms in older women.

A 12-week, randomized, controlled trial assessing the impact of a plant-based diet rich in soy, results of the study indicate adherence to such a diet could reduce moderate-to-severe hot flashes by 84% and nearly 60% of women randomized to this approach became totally free of moderate-to-severe hot flashes.

"This is a game-changer for women aged 45 and over, most of whom we now know can get prompt relief from the most severe and troubling menopause symptoms without drugs," said lead researcher Neal Barnard, MD, president of the Physicians Committee and adjunct professor at the George Washington University School of Medicine, in a 

statement from the Physicians Committee for Responsible Medicine

With vasomotor menopausal symptoms a significant burden on the quality of life among many aging women, the Women's Study for the Alleviation of Vasomotor Symptoms (WAVS) trial was designed to assess compare the effects of implementing a low-fat, vegan diet or no dietary changes on the frequency and severity of hot flashes. Enrolling postmenopausal women reporting at least 2 hot flashes per day, investigators invited more than 7000 patients to take part in the trial. Of these, 155 were interviewed by telephone and a group of 38 met study criteria, underwent randomization in a 1:1 ratio, and were included in the study.

To be included in the study, patients needed to be between 40-65 years of age, without menses in the preceding 12 months, and have experienced their last period within the preceding 10 years. Exclusion criteria included use of hormonal medications, explanation for hot flashes other than natural menopause, use of weight-loss medications, history of drug use, and current consumption of a low-fat, vegan diet.

For the purpose of analysis, frequency and severity of hot flashes were recorded using a mobile phone application and vasomotor, psychosocial, physical, and sexual symptoms were assessed using the Menopause-Specific Quality of Life Questionnaire (MENQOL). Patients were given a self-calibrating scale to track body weight on a day-to-day basis. Potential associations were assessed using t-tests and chi-squared/McNemar tests.

At the end of the trial, data indicated total hot flashes decreased by 79% among those in the intervention group and by 49% among those in the control group (

=.01). Further analysis suggested the frequency of moderate-to-severe hot flashes was decreased by 84% in the intervention group compared to 42% in the control group (

Additionally, investigators noted 59% of patients in the intervention group reported being free of moderate and severe hot flashes from 0-12 weeks (

=.002). In contrast, no change was observed for this variable among those in the control group (between-group 

<.0001). Investigators also pointed out the MENQOL indicated significantly greater reductions in vasomotor (

=.01) domains in the intervention group compared to the control group.

"Previous studies have shown that soy could be beneficial, so we decided to put a diet change to the test," said study author Hana Kahleova, MD, PhD, director of clinical research for the Physicians Committee for Responsible Medicine, in the aforementioned statement. “We believe that the combination is what is important. By the end of the study, the majority of women on a plant-based diet rich in soy reported that they no longer experienced moderate-to-extreme hot flashes at all and that they experienced significant improvements in their quality of life.”

Investigators noted multiple limitations within their study for clinicians to consider when interpreting results. These limitations included the possibility of a placebo effect, a relatively small sample size, limited intervention period prohibited assessment of long-term effects, and the COVID-19 pandemic necessitating use of telemedicine mediums, among others.

The Women’s Study for the Alleviation of Vasomotor Symptoms (WAVS): a randomized, controlled trial of a plant-based diet and whole soybeans for 

postmenopausal women,” was published in 

A 12-week trial found implementing a dietary approach using a low-fat, vegan diet could help reduce the incidence of moderate-to-severe hot flashes in postmenopausal women.

Low-Fat, Vegan Diet Could Help Reduce Hot Flashes, Impact of Menopausal Symptoms in Women

Despite concerns over their impact on cardiometabolic health, new research suggests antidepressant use in those with depression and 

 could lower risk of complications and mortality among these patients.

A retrospective cohort study of Taiwan’s universal health insurance database, results of the 36,000-patient study indicate regular use of antidepressants was associated with a decreased risk of macrovascular complications and all-cause mortality.

"People with depression and diabetes have poorer health outcomes than those with diabetes alone, and regular antidepressant treatment could lower their risk of complications,” said study author Shi-Heng Wang, PhD, of the China Medical University in Taichung, Taiwan, 

Wang, along with a team of colleagues from other institutions in Taiwan, designed the current study with an aim of addressing the current dearth of evidence surrounding the effect of antidepressants on advanced diabetes outcomes. With this in mind, investigators designed their study as a retrospective cohort study using claims data from Taiwan’s National Health Insurance program.

Using this database, investigators identified more than 1.8 million patients with incident diabetes at 20 years or older. After exclusion of those with missing data, those with preexisting conditions, and those with depressive disorder, 36,276 patients were identified for inclusion in the final analyses.

The majority of the study cohort was female and between 45-64 years. Investigators also noted 41.75% had hypertension, 37.5% had dyslipidemia, 6.73% had comorbid chronic liver disease, 11.2% had chronic pulmonary diseases, and 20.26% had been hospitalized in the past year.

The primary outcomes of interest for the analyses was incidence of microvascular complications, microvascular complications, and all-cause mortality. Investigators pointed out plans to further assess associations according to different classes of antidepressants.

Antidepressant use was assessed in 30-days intervals, beginning at 6 months after the cohort entry date, and medication adherence was calculated using the medication possession ratio. Use of medications was classified as none, poor use, partial use, and regular use. For the purpose of analysis, benzodiazepines were used as negative control exposures because they are not involved in glucose metabolism.

Upon analysis, regular use of antidepressants was associated with a 0.92-fold decrease in risk of microvascular complications and a 0.86-fold decrease in risk of all-cause mortality, but not associated with decreased risk of microvascular complications when compared to those with poor use. Further analysis indicated regular use of selective serotonin reuptake inhibitors (SSRI) was associated with a 083-fold decrease in risk of macrovascular complications and a 0.75-fold decrease in risk of all-cause mortality.

Additionally, use of tricyclic or tetracyclic antidepressants was associated with a 0.78-fold decrease in risk of all-cause mortality. Investigators also noted no evidence was observed for associations between regular benzodiazepine use and diabetes complications.

“People who adhere to their antidepressants have better diabetes outcomes and quality of life than those with poor adherence,” said study author Chi-Shin Wu, MD, PhD, of the National Taiwan University Hospital.

Associations Between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus,

The Journal of Clinical Endocrinology & Metabolism.

Analysis of more than 35,000 patients with diabetes and depressive disorder indicates patients with greater adherence to antidepressants appeared to experience fewer complications and a lower rate of mortality than those with suboptimal use. 

Regular Antidepressant Use Linked to Improved Outcomes In Patients with Diabetes and Depression

A new study suggests middle- to older-aged adults consuming at least 3 servings of whole grains daily was linked to lesser declines in glycemic control and blood pressure.

Performed by investigators at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, the analysis of data from the Framingham Heart Study Offspring indicates those who consumed greater amounts of whole grain experienced smaller increases in waist circumference, blood pressure, and blood sugar levels over time.

"Our findings suggest that eating whole-grain foods as part of a healthy diet delivers health benefits beyond just helping us lose or maintain weight as we age. In fact, these data suggest that people who eat more whole grains are better able to maintain their blood sugar and blood pressure over time. Managing these risk factors as we age may help to protect against heart disease," said Nicola McKeown, PhD, study lead investigator and a scientist on the Nutritional Epidemiology Team at the USDA HNRCA,

With an interest in describing how whole and refined-grain consumption might influence cardiometabolic risk profiles, McKeown and a team of colleagues sought to explore potential associations between increased intake of whole grains and refined grain on waist circumference, fasting HDL-C, triglycerides, glucose concentrations, and blood pressure. To do so, investigators designed their study to assess these associations using data from the Framingham Heart Study Offspring Cohort, which included more than 5000 offspring from the original cohort.

Using only patients who completed multiple dietary exams and who were without known diabetes at baseline, investigators identified a cohort of 3121 participants for inclusion in their final analyses. As part of the original study, diet was assessed according to the Harvard semiquantitative food frequency questionnaire (FFQ).

In total, 9231 observations were included in the analyses. The mean number of exams attended was 4 and the median total follow-up time of the study cohort was 18.1 (IQR, 7.0) years. At baseline, the mean age of participants was 54.9±0.17 years, 54.5% were female, and 64.4% reported having overweight or obesity.

After adjustment for confounding factors, results indicated greater intake of whole grains was associated with smaller increases in waist circumference (1.4±0.2 vs 3.0±1.0 cm; 

-trend <.001), fasting glucose concentration (0.7 ± 0.4 vs 2.6±0.2 mg/dL; 

-trend < .001), and systolic blood pressure (0.2±0.5 vs 1.4±0.3 mmHg; 

-trend < .001). Stratification by patient sex suggested a stronger association with waist circumference was present among females than males.

Additionally, results indicated increased intake of whole grains was associated with greater increased in HDL-C and declines in triglyceride concentrations. Investigators did point out this difference failed to maintain significance after adjustment for change in waist circumference. However, results also suggested increased intake of refined grains was associated with greater increases in waist circumference (2.7±0.2 vs 1.8±0.1 cm; 

-trend < .001) and lesser reductions in triglyceride concentration (-0.3±1.3 vs -7.0±0.7 mg/dL; 

"There are several reasons that whole grains may work to help people maintain waist size and reduce increases in the other risk factors. The presence of dietary fiber in whole grains can have a satiating effect, and the magnesium, potassium, and antioxidants may contribute to lowering blood pressure. Soluble fiber in particular may have a beneficial effect on post-meal blood sugar spikes," said Caleigh Sawicki, PhD, MPH, member of the Nutritional Epidemiology Team at the USDA HNRCA.

Whole- and Refined-Grain Consumption and Longitudinal Changes in Cardiometabolic Risk Factors in the Framingham Offspring Cohort

An analysis of data from the Framingham Heart Study Offspring Cohort by investigators at the USDA Human Nutrition Research Center on Aging suggests greater consumption of whole grains was associated with a more preferable cardiometabolic risk profile than lesser consumption or consumption of refined grains. 

Whole Grain Intake Linked to More Preferable Cardiometabolic Profile in Aging Adults, USDA-Funded Study Finds

Data from a 10-year study including more than 800 men suggests testosterone therapy could reduce risk of heart attack and stroke among men with 

Presented at the Annual Congress of the European Association of Urology (EAU21), results of the study indicate men with testosterone deficiency receiving testosterone therapy had a lower risk of mortality and major adverse cardiovascular events than their counterparts who did not undergo testosterone therapy.

"Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5 to 10 years, with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It's clear that this treatment can significantly reduce the risks in this particular group,” said study presented Omar Aboumarzouk, of the Hamad Medical Corporation in Qatar, 

A cumulative registry study designed to assess the long-term safety and efficacy of testosterone therapy in hypogonadal men, the EAU21 study included 805 participants, including 412 receiving 1000 mg of parenteral testosterone every 12 weeks for up to 12 years and 393 who opted against receiving testosterone therapy who served as controls. All patients included in the study were at increased risk of cardiovascular disease due to family history, blood pressure, lipid profile, diabetes status, or body weight.

Upon analysis, results indicated those in the testosterone therapy group had a 10-year mean risk of 22.7% compared to 23.5% among those in the control arm (

=.11). Over a median follow-up of 8 years, 16 deaths occurred in the testosterone therapy group. Investigators pointed out there were no observed incidences of myocardial infarction or stroke among these patients. Over a median follow-up time of 9 years, a total of 74 deaths occurred among those in the control arm. Investigators pointed out 70 incidences of myocardial infarction and 59 cases of stroke were observed among these patients.

Additionally, further analysis suggested use of testosterone therapy was associated with improvements in multiple classical cardiovascular risk factors, including obesity, glycemic control, lipid profile, and CRP.

In the aforementioned statement, Maarten Albersen, Member of the EAU Scientific Office, from Leuven University in Belgium, commended study authors for their study’s addition to the existing knowledge base but cautioned more research into the effects of testosterone on cardiovascular health is needed before drawing a definitive conclusion.

“These were men with a medium risk of heart attack or stroke, and those receiving testosterone were younger and had a slightly lower risk at the start of the study. The study was long enough to see differences in the rate of cardiovascular events,” pointed out Albersen. “However, the numbers involved and the fact that the trial was not randomised mean it's still difficult to draw any hard conclusions. A new trial is now underway, aiming to recruit 6000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone."

This study, “Less mortality and less Major Adverse Cardiovascular Events (MACE) under long-term Testosterone Therapy (TTh): 15-year data from a prospective controlled registry study,” was presented at the Annual Congress of the European Association of Urology.

A study from the Annual Congress of the European Association of Urology suggests undergoing testosterone therapy could improve cardiovascular health and reduce risk of adverse events in men with hypogonadism.

Testosterone Therapy Could Improve Cardiovascular Health in Men with Hypogonadism

As Endocrinology Network continues to grow and looks to engage more clinicians involved in endocrinology, we have also added members to our editorial advisory board. Our eyes and ears in the field, our advisory board members help guide coverage to position us to provide high-quality editorial content for endocrinologists and clinicians with an interest in endocrinology. To allow our readers, viewers, and listeners an opportunity to become better acquainted with our advisory board members, we are launching the Endocrinology Network Meet the Board series. Periodically, we will be launching content highlighting our advisory board members and the reasons why they were chosen to help lead Endocrinology Network as we look to expand our audience and solidify our position as a leader in endocrinology news.

In this edition of Meet the Board, you will be introduced to Elaine Apperson, MD, Pediatric Endocrinologist with Prisma Health. In her own words, Dr. Apperson describes how she humanizes the pediatric endocrinology experience for her patients and their caregivers. A sometimes-daunting experience, Dr. Apperson found a simple, patient-centered conversation at the end of visits can often go a long way in easing the burden placed on families when a child is diagnosed with diabetes.

Let me start from the very beginning. The first concept that I started to tell people, when I would talk about diabetes to those who had no exposure to diabetes, especially diabetes and children, was that diabetes was unique—there is no other condition, that I could think of, where we expected the patient to maintain, to all external views, a life that continued to appear completely normal to the outside world. Their sports, their school, extracurriculars, everything. There is no bump and there is no sick role to be played and, yet we're asking the parents and the patient to completely take on almost 24-hour burden of blood sugar monitoring, insulin administration, changes in diet, learning how to count carbohydrates, and the additional emotional toll of checking and dealing with frustrations of not knowing why blood sugars were going up and going down without any sort of identifiable reason.

Patients with asthma also have a burden, but their burden is intermittent. Patients with cystic fibrosis also have a burden, that burden from medical standpoint is pretty heavy, but we don't expect our patients with cystic fibrosis necessarily to be the star on the swim team or to attend school full time. So, they have a sick role. Whereas our persons with diabetes, they take all of this on, but nobody expects them to sit out. I mean, they can sit out or their parents can make allowances for them or not expect them to do certain things and that's okay, but for a lot of the time we sort of say, "Okay, you have diabetes, but you're still going to do this and that and the other,", and that is what we want for our patients: we don't want them to miss out.

That's the way I started to describe diabetes is that we want to do two things at the same time. I want you to maintain your health and safety, but I also want to fit diabetes into your life instead of fitting your life around diabetes, because we can do it within reason.

I tried to explain diabetes to my friends and to my family, as such, to give them sort of an inside peek of what these families go through in terms of having to carry on with this burden and then carry on in the big sense and what that meant and how exhausting it was.

Over time, I've evolved that concept into all the contingencies that come with diabetes, and the fact that we see these patients for such a short period of time at their visit. There's no way in the world that we can touch on all the possible contingencies of diabetes: what do you do when you've just given insulin for a meal and you see your butcher going higher and higher, but you've just given the insulin? How do you know when to give another dose of insulin or you're going off and you're going out to play, you've just had a big snack, but you see your blood sugar going down a little bit more? When do you know to how to eat more, you know, and how fast is your blood sugar going down?

There's no way in a 30-minute clinic visit that you can touch on every possible scenario that could come up in the course of you having diabetes that might occur in the next 90 days, especially if the child is young, especially if it's new, especially if you've got to send the prescription in, order some labs, and all that sort of stuff. So, we're never going to get to everything that can possibly happen in that 30-minute window. I also started to think about how I felt when I went to the doctor and the doctor breezed in said some stuff and then breezed out. I'm kind of left sitting there and I didn't even really understand what he or she said, and I really didn't even get a chance to ask some of the questions I had, I might have even forgotten some of my questions, and then I drove home. And I didn't go in being anxious, necessarily, but I certainly left feeling a little unsettled.

I didn't feel seen, I didn't feel heard, and I think that that would be exacerbated to the 10th degree if it was a child that I had and if it was 24 hours a day, seven days a week, 365 days a year kind of burden. It could be really, really scary, because it involves numbers and life and death, and every single thing that I did with that child every single day.

I think it was Maya Angelou who said it: “People will forget what you said, people will forget what you did, but people will never forget how you made them feel”. That really resonates with me and I thought I can't do it all, I can't be it all, I can't answer every question that somebody might have, but I certainly can try to have a family, a caregiver, a parent, whoever it may be, and the child, by extension, because a child can pick up, they can listen to the tenor of the conversation, they may not understand that they certainly can pick up the temperature in the room, the tone of the conversation, the facial expression on their caregiver's face, my facial expression, how we wrap up the visit, how it feels, and they can certainly pick up how it feels on the ride home.

So, I thought let's just wrap it up. Even if there are unanswered questions, even if there's still a lot of fear and apprehension, still, let's still try to wrap it up in a manner that is reassuring. So, I thought let's bring it back up to a level where we're conversing. Maybe we talk about something nondiabetes-related. That's when I said, this is kind of where I live, I kind of live at work, you know, this is a familiar place to me. Although it sort of becomes one for our patients who are here long term. So, I thought, let me just escort the patient out and as I'm doing so, we're sort of wrapping up the room.

I'll generally review what we've done, what we've talked about, what we've changed, the high points of our discussion, and when we're going to follow up. I always reiterate that we're here 24 hours a day, 7 days a week by phone for any of those contingencies that will arrive. so that we don't have to cover everything. Then, ahead of walking out we make sure we have everything, walk out, walk up to the front desk, and, usually, I’d talked to the receptionist and compliment the child on how well they did for their exam. And for the visit, talk to the mom about something nondiabetes-related about the weather or something like that. I tell the receptionist we need our school excuse, and this is when we're going to do follow-up and if they need to go down to the laboratory for labs or something like that.

I just want that family to drive home knowing that I don't see them just as a diabetes patient, but as a real person or real people acknowledging that they're probably going back to school or that they're going to play sometime later in the day and they're just not numbers. I want their ride home to be calm and maybe we tell a joke or something like that. So, maybe they're leaving with a smile on their face. That's just really important because there are always going to be unanswered questions. There's always going to be apprehension with diabetes, along with apprehension comes fear, and you can't necessarily, as a provider for patients with diabetes, alleviate all of that.

But at least you can make the visits for the caregiver and the patient be less fraught, less of a time of feeling like it might be a place where they're criticized or where they're going to become even more confused or feel even more alienated. We sit here with all our knowledge and all our right answers, and they feel like they're inept or don't know what they're doing.

The point is for them to feel like they're just like me. A lot of times they don't know what to do and I really may not know, but I just do the best I can, and I tell them that they're just doing the best they can. My answers sometimes are no better than their answers. So, I think it has made me much more joyful in my practice, and I think it has made it better for my patients as well.

This transcript has been edited for clarity.

To allow our audience to become more acquainted with our advisory board members, Endocrinology Network will be hosting a special content series highlighting our board members, their practices, and why they were invited to help guide coverage moving forward. 

Endocrinology Network's Meet the Board: Elaine Apperson, MD

Endocrinologists, diabetes specialists, and nephrologists had a new weapon added to their arsenal thanks to the US Food and Drug Administration’s approval of finerenone (Kerendia) for treatment of patients with chronic kidney disease associated with type 2 diabetes.

With approval based on the results of the phase 3 FIDELIO-DKD trial, finerenone becomes the first and only nonsteroidal mineralocorticoid receptor antagonist approved by the US FDA for adults with chronic kidney disease associated with type 2 diabetes.

“The patient population included in the trial that supported the approval of KERENDIA were at risk of chronic kidney disease progression despite receiving standard of care treatment to control blood pressure and blood glucose,” said George Bakris, MD, University of Chicago and lead FIDELIO-DKD study investigator, 

 “In people with chronic kidney disease associated with type 2 diabetes, physicians now have a new treatment to provide kidney protection.”

Indicated for reducing the risk of sustained eGFR decline, kidney failure, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in patients with chronic kidney disease associated with type 2 diabetes, excitement around finerenone has been building since the trial was published in 

and presented at ASN Kidney Week during October 2020.

A randomized, double-blind, placebo-controlled trial enrolling more than 5600 patients, FIDELIO-DKD compared finerenone versus placebo therapy and found use of finerenone was associated with an 18% reduction in risk for progression of chronic kidney disease and a 16% reduction in risk of the composite cardiovascular endpoint. Recently, a trio of prespecified analyses from the trial presented at ADA 2021 demonstrated the agent provided consistent effectiveness, irrespective of baseline insulin, GLP-1 RA, and SGLT2 inhibitor use. These analyses even suggested concomitant use with SGLT2 inhibitors could result in an additive effect on the renoprotective effects of these agents.

 notes the recommended starting dosage is 10 mg or 20 mg orally once daily, depending on eGFR and serum potassium thresholds. The dosage is then increased after 4 weeks to the target dose of 20 mg once daily.

The prescribing information also notes the agent is contraindicated against concomitant use with strong CYP3A4 inhibitors and among patients with adrenal insufficiency. Additionally, prescribing information listed hyperkalemia, hypotension, and hyponatremia as common adverse reactions seen with finerenone.

“Chronic kidney disease associated with type 2 diabetes can have such a debilitating impact on patients’ lives.10 Unfortunately, this disease is far reaching, as up to 40 percent of all patients with type 2 diabetes develop chronic kidney disease,” said Kevin Longino, CEO of the National Kidney Foundation, and a kidney transplant patient. “It is important for physicians and patients to have new treatment options that can slow chronic kidney disease progression.”

In the aforementioned statement, Bayer noted the expectation that finerenone would be available in the US beginning the end of July 2021. Additionally, the release noted finerenone is awaiting marketing authorization in the European Union.

With approval on July 9, finerenone (Kerendia) becomes the first nonsteroidal mineralocorticoid receptor antagonist to receive approval for use in adults with chronic kidney disease associated with type 2 diabetes.

Finerenone (KERENDIA) Approved for Chronic Kidney Disease Associated with Type 2 Diabetes

 reached out to Diana Isaacs, PharmD, Clinical Pharmacy Specialist and the Remote Monitoring Program Coordinator at the Cleveland Clinic, to take part in our coverage of the annual meeting. Isaacs compiled a list and created a video detailing her top picks for CGM-related data presented at the conference. 

597-P: Long-Term A1C Outcomes with and without Intermittent CGM Use in Adults with T2D Participating in the Onduo Program

Virtual Diabetes Clinic offers remote care, including a mobile app, remote lifestyle coaching, video consultations with endocrinologists, to type 2s.

Patients who are “high risk” are also offered prescriptions for intermittent-use Dexcom G6 CGMs.

This retrospective analysis included baseline, six-month, and one-year data from 772 participants, of whom 46% (n=354) used CGM and 54% (n=418) did not use CGM.

Dexcom G6 users saw a 0.7% A1c reduction to 7.2% at one year, a significantly greater improvement relative to those not using CGM, who saw only a 0.2% reduction to 7.4% (p<0.001).

Even more impressive, CGM users with baseline A1c values >9% saw a 2.8% A1c reduction to 8.0% at one year, a significantly greater improvement relative to a 1.8% reduction to 9.0% among non-CGM users (p=0.006).

Included people with type 2 diabetes not on insulin.

Successful Use of CGM in Primary Care Depends on Patient Support and Workflow-Lessons from the Mobile Study

Presented during a symposium by Thomas Martens, MD

Effect of CGM on Glycemic Control in Patients with Type 2 Diabetes Treated with Basal Insulin

Recruited individuals in primary care practices

Compared rtCGM vs BGM in management of T2D on basal insulin

Enrollment: age >30 years, A1C 708-11.5, basal insulin with any other therapies (no prandial)

Randomized 175 individuals 2:1 to CGM vs BGM

Average age 57, 53% minor rate or ethnicity, mean A1c=9.1%

Advisors reviewed data and forwarded to primary care clinician

All active diabetes management iremianed in primary care.

Findings: greater decrease in A1C over 8 months in CGM vs glucose monitors (1.1% vs -0.6%).

CGM group had significantly better time in range 70-180.

Strategies for implementing CGM technology: get access to the data, use the data, cadence of titration

Accuracy of Dexcom G6 Continuous Glucose Monitoring in Non–Critically Ill Hospitalized Patients With Diabetes 

Presented at a Dexcom sponsored section by Guillermo Umpierrez, MD

Dr. Umpierrez read out the data that showed Dexcom G6 is accurate in hospital settings.

The newly published retrospective study, which included 205 insulin-treated type 2 diabetes patients wearing Dexcom G6 in general medicine and surgery wards, found that 98.6% of data fell in Zones A and B of a Clarke Error Grid.

The researchers found no difference in accuracy based on race, BMI, arm vs. abdomen placement, and eGFR.

However, the MARD was significantly higher in the hypoglycemic range (<70 mg/dl) at ~18%, as compared to ~11%-12% at all other glycemic ranges.

Dr. Umpierrez noted that this issue may suggest that providers should perform point-of-care testing when CGM readings <80 mg/dl in hospital settings.

The accuracy also dropped significantly in patients with severe anemia (hemoglobin <7 g/dl) with a MARD of ~17%.

Looking ahead, Dr. Umpierrez highlighted a G6 intervention study comparing the glycemic control achieved through insulin adjustment by point-of-care testing vs. insulin adjustment by CGM readings in hospitalized insulin-treated type 1s and type 2s. Per Dr. Umpierrez, the study has just completed, and we’ll be keeping an eye out for its publication.

600-P: Real-Time CGM Coverage Eligibility Should Include Type 2 Diabetes Patients Treated with Less-Intensive Therapy

Investigator-initiated, 6-month, prospective, interventional, single-arm study assessed the effects of rtCGM use in T2D patients treated with basal insulin only or non-insulin.

Clinic visits occurred at baseline and every 3 months per usual care.

The primary outcomes were changes in A1C and percent of time in range (%TIR), above range (%TAR) and below range (%TBR).

Time in range increased from 57% to 68.4% 3 months) to 72.2% at 6 months

Expanding insurance coverage to T2D patients treated with less-intensive therapy may help improve glycemic control within the broader diabetes population.

136-LB: Budget Impact of Adding Flash Continuous Glucose Monitoring (CGM) to Medicaid Formularies

The authors compared the cost of increased FreeStyle Libre adoption against the cost savings resulting from reduced severe hypoglycemia and DKA events. 

With nearly 1.1 million people on intensive insulin therapy enrolled in Medicaid (~370,000 type 1s and ~690,000 type 2s), the calculation assumed FreeStyle Libre adoption in this group would grow from a hypothetical 23% to 33% with universal coverage for FreeStyle Libre.

This would result in an extra $121 million in cost to cover glucose monitoring in this population per year. Using published data, the analysis then assumed rates of DKA and severe hypoglycemia events would be cut by ~50% for those who initiated FreeStyle Libre. This would result in cost savings of $74 million per year.

Additionally, the calculation assumed FreeStyle Libre would deliver an A1c reduction of ~0.5% for type 1s and ~0.9% for type 2s; this would result in annual cost savings of $66 million.

Adding things up, the calculation estimates $19 million in annual cost savings for national Medicaid expenditure.

Diana Isaacs, PharmD, offers perspective on her top 5 CGM-related studies or presentations from the American Diabetes Association's 81st Scientific Sessions.

ADA 2021 Expert Perspective: Dr. Diana Isaacs's Top 5 CGM Studies

The US Food and Drug Administration (FDA) has approved exenatide extended-release (BYDUREON BCise) for improving glycemic control in pediatric patients aged 10-17 years with type 2 diabetes as an adjunct to exercise and diet.

press release from AstraZeneca on July 23

, exenatide extended-release becomes the first once-weekly GLP-1 receptor agonist treatment to receive approval in pediatric populations.

“The US FDA approval is an important milestone for the treatment of children with type 2 diabetes. BYDUREON BCise brings an important new therapeutic option to physicians caring for children with this chronic disease that can lead to serious long-term issues if not adequately treated,” said William Tamborlane, MD, Department of Pediatrics, Yale School of Medicine, in the press release.

According to AstraZeneca, approval for exenatide extended-release in this new patient population is based on the results of the phase 3 BCB114. Of note, exenatide extended-release (BYDUREON) became the first once-weekly therapy approved by the US FDA for improving glycemic control in patients with type 2 diabetes in 2012 and BYDUREON BCise received approval in 2017 as an auto-injector device.

BCB114 compared exenatide extended-release to placebo therapy in adolescent patients with type 2 diabetes over a 24-week period. The trial, which also included a 28-week open-label extension period, enrolled 82 patients aged 10-17 years treated with diet and exercise along or in combination with a stable dose of oral anti diabetic agents and/or insulin. Results of the trial demonstrated use of exenatide extended-release was associated with significantly greater mean change in HbA1c compared to placebo.

The release from AstraZeneca also noted adverse reactions observed in the pediatric population used in the study were consistent to those seen in adult populations. Additionally, the release points out the safety and efficacy of exenatide extended-release has not been established in patients younger than 10 years old.

“This decision is an important milestone for the care of this younger patient population by providing a convenient, once-weekly treatment option. The Phase III data that supported this approval demonstrated the safety and tolerability of exenatide extended-release in younger patients was similar to the proven safety profile of this medicine in adults.”

With approval, exenatide extended-release (BYDUREON BCise) becomes the first weekly GLP-1 RA therapy to receive approval for improving glycemic control in pediatric patients aged 10-17 years with type 2 diabetes.

Exenatide Extended-Release Receives Historic FDA Approval for Use in Pediatric Type 2 Diabetes

 could help predict risk of adverse pregnancy outcomes for mother and offspring, according to a new study from Northwestern University Feinberg School of Medicine.

A cross-sectional analysis of maternal and fetal data from the National Center for Health Statistics, results of the study demonstrate the presence or absence of 4 specific cardiovascular risk factors, including BMI and diabetes status, before pregnancy could help predict risk of adverse outcomes, including maternal ICU admission, preterm birth, low birthweight, and fetal death.

"Individual cardiovascular risk factors, such as obesity and hypertension, present before pregnancy have been associated with poor outcomes for both mother and baby," said study lead investigator Sadiya Khan, MD, Assistant Professor of Cardiology and Epidemiology at Northwestern University Feinberg School of Medicine, in 

a press release from the European Society of Cardiology

. "Our study now shows a dose-dependent relationship between the number of risk factors and several complications. These data underscore that improving overall heart health before pregnancy needs to be a priority."

To learn more about how presence of cardiovascular risk factors might influence 

, Khan and a team of colleagues from the Feinberg School of Medicine, including AHA President Donald Lloyd-Jones, MD, designed the current study to identify the total burden of prepregnancy cardiovascular risk factors among pregnant women. Investigators designed their study as cross-sectional analysis of data from the National Center for Health Statistics. Using the database and a time frame of interest defined as 2014-2018, investigators performed a search of patient data related to births to women aged 15-44 years during this time frame.

Cardiovascular risk factors of interest for the investigators’ analysis included BMI, smoking status, presence of hypertension, and presence of diabetes. Patients were categorized according to the number of risk factors present prior to becoming pregnant, with scores ranging from 0-4.

In total, 18,646,512 pregnancies were identified for inclusion. The study cohort had a mean maternal age of 28.6 (SD, 5.8) years, 53.6% were non-Hispanic white, and more than 60% had at least 1 prepregnancy cardiovascular risk factor. Overall, 52.5% reported having 1 risk factor while 7.3%, 0.3% and 0.02% reported having 2, 3, and 4 risk factors, respectively. Compared to their counterparts with no risk factors, women with at least 1 risk factor had lower educational attainment (79.5-85.3% vs 88.7% graduated high school), less receipt of prenatal care (97.8-98.5% vs 98.7%), higher prevalence of multiparty, and a higher prevalence of prior spontaneous or induced pregnancy loss.

In analyses adjusted for maternal age at delivery, race/ethnicity, education, receipt of prenatal care, parity, and birth plurality, investigators found grades associations between increasing number of prepregnancy risk factors and increased risk of adverse outcomes. Compared to those with no risk factors, risk of maternal ICU admission was increased 1.12-, 1.86-, 4.24-, and 5.79-fold increase in risk among those with 1, 2, 3, and 4 risk factors, respectively.

Investigators noted women with all 4 risk factors had a 5.8-fold greater risk of maternal ICU admission, 3.9-fold greater risk for preterm birth, 2.8-fold greater risk of low birthweight, and 8.7-fold greater risk of fetal death compared to those with no risk factors. Investigators also pointed out individual components of the risk factor score were directly associated with adverse outcomes, with heterogeneity in effect sizes; however, this effect was not seen with BMI, which was inversely associated with low birth weight.

“Levels of prepregnancy obesity and high blood pressure are rising and there are some indications that women are acquiring cardiovascular risk factors at earlier ages than before,” added Khan. “In addition, pregnancies are occurring later in life, giving risk factors more time to accumulate. Taken together, this has created a perfect storm of more risk factors, earlier onset, and later pregnancies.”

Analysis of more than 18 million pregnancies sheds light on the impact various prepregnancy cardiovascular risk factors, including BMI, smoking status, and diabetes, can have on risk of adverse maternal and fetal outcomes. 

Exenatide Extended-Release Receives Historic FDA Approval for Use in Pediatric Type 2 Diabetes

Prepregnancy Cardiovascular Risk Factors Play Role in Risk of Adverse Maternal, Fetal Outcomes

Cognitive Decline in Older Women Could Signal Bone Loss, Increased Fracture Risk

FDA Issues Letter to Ardelyx Detailing Deficiencies in Application for Tenapanor

Dapagliflozin Safe and Effective in Stage 4 Chronic Kidney Disease, DAPA-CKD Analysis Finds