How Recent Developments Impact Insulin Affordability

Insulin for All?

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.

For all the attention that has been brought to the ongoing diabetes epidemic in recent years, many endocrinologists and other members of the diabetes care team argue forms of diabetes outside of 

 are still overlooked and underrecognized.

rates of gestational diabetes have been increasing

 in the US across all ethnicities and racial subgroups over the last 20 years, highlighted this very fact. With presence of diabetes increasing the risk for other cardiometabolic comorbidities, identification of avenues for improving diagnosis and management of gestational diabetes could have a profound impact on the disease state as a whole.

During the Metabolic Institute of America’s (TMIOA) 5th Heart in Diabetes sessions in New York, NY, Erica P. Gunderson, PhD, MS, MPH, a senior research scientist in the Kaiser Permanente Northern California Division of Research, led a presentation centered around gestational diabetes, insulin resistance, and prognostic value of coronary artery calcium in women based on data from analyses of the CARDIA study.

To learn more about the management of gestational diabetes in 2021 and her presentation, our sister publication 

 sat down with Gunderson following her presentation at the conference. Learn more about her perspective in the video below.

Videos

Erica P. Gunderson, PhD, MS, MPH, offers perspective on the current state of gestational diabetes management as well as avenues for improving current diagnostic and management standards. 

Improving Awareness and Management of Gestational Diabetes, With Erica Gunderson, PhD

“The discovery of insulin was a tremendous landmark in medicine. People were dying, kids were dying within 6-12 months of diagnosis—wasting away.”

has been highlighting the 100-year anniversary of the discovery of insulin through hosting the perspectives of those involved with diabetes management. In recent months, we’ve showcased a 3-part video series on insulin affordability and how recent advances could influence pricing as well as written perspective from an internal medicine resident with type 1 diabetes reflecting on how his personal journey with insulin use.

To continue our celebration of Sir Frederick Banting and the 100th anniversary of the discovery of insulin, we’re hosting a portion of a video interview from our sister publication 

 with Vivian Fonseca, MD, chief of endocrinology at Tulane University School of Medicine. Recorded at the Metabolic Institute of America’s 5th Heart in Diabetes Meeting, Fonseca provides his perspective on the importance of the discovery 100 years later and how the role of insulin has evolved since its initial discovery.

Vivian Fonseca, MD, reflects on the 100-year anniversary of the discovery of insulin and how the role of insulin has evolved since Sir Frederick Banting's historic discovery. 

Reflecting on 100 Years of Insulin, With Vivian Fonseca, MD

SGLT2 inhibitors have made major headlines in recent years with revelations of their cardiorenal protective benefits, but endocrinologists and cardiologists alike have pointed out use agents within the class does not provide a reduction in risk of stroke.

The topic of the role of diabetes medications in stroke prevention was the focus of a discussion led by Silvio Inzucchi, MD, professor of medicine at the Yale School of Medicine, at The Metabolic Institute of America’s (TMIOA) 2021 Heart in Diabetes sessions in New York, NY. During his discussion, Inzucchi provided an overview of the effects of newer diabetes medications on stroke but also touched upon potential reductions observed with more entrenched staples of diabetes management.

After his presentation at Heart in Diabetes, our sister publication 

 sat down with Inzucchi for more insight into his presentation and the role of diabetes medications in stroke prevention.

Silvio Inzucchi, MD, discusses his presentation on the role of diabetes medications, including SGLT2 inhibitors and GLP-1 RAs, in stroke prevention from TMIOA's 5th Heart in Diabetes conference. 

Silvio Inzucchi, MD: Stroke Prevention and Diabetes Medications

In a presentation at The Metabolic Institute of America’s (TMIOA) 2021 Heart in Diabetes sessions in New York, NY , Andrea Dunaif, MD, Professor of Medicine in the Department of Medicine and new Chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes and Bone Disease for the Mount Sinai Health System, spoke of what she describes as an “ongoing controversy” regarding the potential increased risk for cardiovascular disease in women with 

“Tremendous advance have been made in the past 10 years on elucidating causal pathways through genetic pathways,” Dunaid said.

Androgen production, granulose cell function, and age in menopause were considered some of the causal pathways.The causality of insulin resistance had also been proven in studies that showed the genes that cause resistance and increased body mass index also contributed to PCOS. Dunaif cited the Rotterdamn Criteria, diagnostic criteria developed in recent years that focused on key clinical features such as hyperandrogenism, ovulatory dysfunction, and poor metabolic outcomes.

“These are the women that have profound insulin resistance, and there’s pretty good data that they’re about, independent of obesity, at 4-fold increased risk of type 2 diabetes with a significantly younger age of onset,” Dunaif said.

Dunaif added that younger women with PCOS who have developed type 2 diabetes due to the disease were likely at marked cardiovascular disease risk. Despite ongoing discussions of the potential cardiovascular risk associated with the disorder, little data exists on the subject.

“Unfortunately, there have been no long-term respective cohort studies to an age which women start having increased events to answer this question,” Dunaif said. “So, we’re left with other types of data.”

An increased risk of cardiovascular disease was recorded in an early Scandanavian study involving 18,112 patients with PCOS, but the data focused solely on younger female patient populations.

A similar cohort study in Denmark, which offered a more robust definition of PCOS, observed the long-term health trajectory of older women with the disease and also found an increased risk of cardiovascular disease.

study found that women with irregular menstrual cycles found a 1.5 increased risk for cardiovascular events. Though incomplete, Dunaif considered it to be the best data on the subject of PCOS and cardiovascular health.

Aside from the limited studies, Mandelian Randomization has been a key component in the study of PCOS and the potential link to cardiovascular risk.

Mandelian Randomization uses genetic variants that are correlated with exposure to PCOS, such as body mass index, to determine a causal relationship. However, much of the data requires corroboration.

Overall, though women with PCOS have not been studied to an age when cardiovascular events are considered common, Dunaif noted that the risk of type 2 diabetes by 4-fold, and the disease was linked to several traditional and emerging CVD risk factors.

At the end of the presentation, Dunfaid added that menses continue to act as a “vital sign” for cardiovascular disease, and urged patients and clinicians to incorporate the test.

“Menses that (patients are) either skipping or cycle lengths greater than 40 days are associated with increased risk across a lifespan for type 2 diabetes, and even more concerning, with premature mortality,” Dunaif said. “So, 1 simple question and you can really help your patients.”

Articles

An overlooked aspect of an under-discussed condition, Andrea Dunaif, MD, provided an overview of the cardiovascular risk seen among women with polycystic ovary syndrome. 

Understanding Cardiovascular Risk in Polycystic Ovary Syndrome, With Andrea Dunaif, MD

Data from a 12-week trial assessing the effects of a low calorie, low carbohydrate diet in patients with type 2 diabetes is highlighting the impact of diet in the remission of 

Results of the trial, which compared a low calorie, low carbohydrate diet against usual treatment, provided results indicating implementing such a dietary intervention through a pharmacist-led team could reduce the need of glucose-lowering medications in patients with type 2 diabetes.

“Type 2 diabetes can be treated, and sometimes reversed, with dietary interventions,” said trial investigator Jonathan Little, PhD, associate professor at the University of British Columbia’s Okanagan School of Health and Exercise Sciences,

 “However, we needed a strategy to help people implement these interventions while keeping an eye on their medication changes.”

With interest and research into the effects of nutrition at an all-time high, Little and colleagues from the University of British Columbia and Teesside University in England sought to assess whether use of a delivered through community pharmacists could reduce the need for glucose-lowering medications among adult patients with type 2 diabetes. With this in mind, the Pharmacist-led Therapeutic Nutritional Intervention in Type 2 Diabetes was designed as a pragmatic, community-based parallel-group randomized controlled trial comparing the effects of a low calorie, low carbohydrate diet to typical treatment over a period of 12 weeks in a population of patients aged 30-75 years, with a diagnosis of type 2 diabetes from a physician, and a BMI of 30 kg/m2 or greater.

Conducted across 12 different community pharmacies within southern British Columbia, Canada, the trial had a primary outcome measure of use or nonuse of glucose-lowering medications after conclusion of the 12-week study period. The trial also included changes in HbA1c, glucose-lowering medication dose, BMI, body weight, and waist circumference, among others. Patients included in the trial randomized to the dietary intervention were provided with a free-of-charge diet plan that consisted of individuals food choices selected within the diet plan. Investigators noted the daily macronutrient content equated to fewer than 50 grams of carbohydrates, 35–45 grams of fat, and 110–120 grams of protein for a total of 850–1100 kcal.

Additionally, patients randomized to the intervention arm of the study took part in weekly visits to a pharmacy for visits with a lifestyle coach and pharmacist to monitor progress, collect intervention foods, and assess medication usage.

Overall, 188 patients were rolled in the trial. Of these, 98 were assigned to the intervention arm and 90 were assigned to the standard treatment arm. Investigators pointed out 78 of the 98 patients in the intervention arm completed the intervention and 60 of the 90 in the typical treatment arm completed the trial.

Upon completion of the trial, results suggested the low calorie, low carbohydrate intervention was associated with a reduction in need for glucose-lowering medications through complete discontinuation of medications, which occurred in 35 patients in the intervention arm and 0 patients in the typical treatment arm (

 <.0001). Investigators pointed out patients in the dietary intervention arm also had reduced medication effect scores compared to the typical treatment arm, with these reductions occurring concurrently with clinically meaningful improvements in HbA1c, anthropometrics, blood pressure, and triglycerides (

In a safety analysis, 4 adverse events were observed among patients in the intervention arm and none reported in those within the typical treatment arm. Of the adverse events reported, 2 were related to mild hypoglycemia in patients reluctant to reduce insulin dosages to the recommended amount, 1 was related to hypoglycemic symptoms but none of the measured blood glucose values were lower than 5.2 mmol/L, and the final adverse events was a cardiac event occurring 3 weeks into the trial deemed unrelated to the intervention by a data safety and monitoring board.

“Community pharmacists have expertise in medication management and can serve an important role in overall diabetes care,” said Little. “When Type 2 diabetes patients follow a very low-carbohydrate or low-calorie diet, there is a need to reduce or eliminate glucose-lowering medications. Community pharmacists are ideally positioned to safely and effectively deliver interventions targeted at reducing diabetes medications while promoting Type 2 diabetes remission.”

A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes

A 12-week trial assessing the effects of a low calorie, low carbohydrate diet facilitated by community pharmacists suggests this approach could contribute to the remission of type 2 diabetes in adult patients. 

Pharmacist-Led Dietary Interventions Could Contribute to Diabetes Remission

: An elderly lady with a history of diabetes mellitus who just switched from metformin to insulin is BIBA for sweats, light-headedness, nausea, and SOB, all lasting about 1 hour. Her glucose was measured at 68 by medics and symptoms resolved after juice and food that she was consuming as medics arrived. She denies any chest pain, abdominal pain, vomiting, or other complaints.

: Vital signs are normal as is her physical exam other than visible diaphoresis

Computer Read: Atrial pacemaker at 60 bpm, marked LAD, ST deviation and T-wave abnormalities consider inferior and anterolateral ischemia.

Our latest endocrine case report from Brady Pregerson, MD, features an elderly woman with a history of diabetes experiencing sweats, light-headedness, nausea, and SOB. Can you determine the correct diagnosis?

Endocrine Case Report: Hypoglycemia and Abnormal EKG

This article was originally published on 


A recent analysis of retinal findings from a population of patients with diabetes in Norway is providing an overview of the effect of dietary intake of marine polyunsaturated fatty acids (PUFAs) on the development of diabetic retinopathy.

Results of the study, which was led by Knud Erik Alsbirk, MD, of Sotra Eye Clinic, suggested no patients in the study had best-corrected visual acuity (BCVA) lower than 0.3 (log MAR 0.48) as a result of diabetic retinopathy.

A total of 514 patients with diabetes were recruited from November 2009 - March 2011, with 4 dropping from the study after refusal. Of the total patient population left, 50 patients with type 1 diabetes (40% females) and 460 patients with type 2 diabetes (47.4% females) were included, with all patients having ≥1 year duration of diabetes.

All patients were scheduled for routine follow-up at an ophthalmological practice in the study area, which serves a population of 40,000 in the local Norwegian communities.

During follow-up, data was collected including demographics, BCVA in right and left eye, and severity of retinopathy after dilation. In addition, investigators collected data on the existence of vision-threatening diabetic retinopathy (VTDR), with a DME grade ≥2 or PDR.

Patients also reported medical parameters, including level of HbA1c, use of antihypertensive medication and statins, as well as self-reported diet history of estimated weekly intake of fish foods and weekly use of PUFA supplements.

Investigators analyzed the association between intake of fish oils and visual acuity through linear regression for BCVA and logistic regression for DME (DME >1) and DR (DR >0).

Analysis of the data show the median age of the type 1 diabetes group and the median diagnosed duration was 11.5 years. Data also show HbA1c levels were found in 92% of the patients, with 39% of patients using antihypertensive medication and 34% using statins.

Further, the type 2 group had a median diagnosed duration of 8 years and a mean age of 66 years. A total of 84% knew their HbA1c levels, with 66% of patients using antihypertensive medication and 64% taking statins.

The type 1 group (n = 50) showed 48% of patients had photographic evidence of diabetic retinopathy, with 8 patients (16%) having proliferative retinopathy (PDR) and 6 patients (12%) having diabetic macular edema (DME), grade 1 or 2. All patients had a BCVA of 0.5 (log MAR 0.3) in the better or best eye.

Additionally, in the type 2 group (n = 460), 23.6% had DR, 3% had PDR, and 5% had DME. In addition, 19 patients had VTDR.

Data also show 7 patients (1.5%) had best eye VA worse than 0.3 (log MAR 0.48) and 98% of patients had VA at or better than 0.5 (log MAR 0.3) in the best eye.

Also, investigators noted the average number of fish meals per week was 3.2 in the type 1 group and 4.4 in the type 2 group. The data collection shows 44% of type 1 patients and 55% of type 2 patients took omega-3 supplements regularly.

Investigators concluded the 0.4% of severe extraocular microangiopathy and best preserved eye VA indicated a low level of serious microvasculopathy.

They noted timely ophthalmological care in diabetes patients would benefit prevention of visual and systemic impairment in one of the leading worldwide causes of blindness and morbidity.

“It seems safe to conclude that daily normal intake of fatty fish and/or fish oils may prove to be an important low-cost prophylaxis against diabetic microangiopathy with little risks,” investigators wrote. “Further carefully designed multicenter studies including monitoring of serum PUFA levels are needed to settle this important issue.”

Diabetic retinopathy and visual impairment in a Norwegian diabetic coast population with a high dietary intake of fish oils. An observational study

A 3-year study with more than 500 patients, results suggest none of the study participants had a BCVA worse than 0.3 (log MAR 0.48) due to diabetic retinopathy. 

Polyunsaturated Fatty Acids Could Protect Against Diabetic Eye Disease

The US Food and Drug Administration (FDA) and the Federal Trade Commission (FTC) have warned a total of 10 companies for illegally selling dietary supplements claiming to treat or prevent 

 on September 9, the organizations posted warning letters to the 10 companies for violating the Federal Food, Drug, and Cosmetic Act by illegally selling dietary supplements that claim to cure, treat, mitigate, or prevent diabetes.

"More than 34 million Americans— just over 1 in 10 people— are living with diabetes. Dietary supplements that make fraudulent claims to treat diabetes are unapproved new drugs that could potentially harm consumers who use these products instead of seeking safe and effective FDA-approved treatments,” said Cara Welch, PhD, Acting Director of the Office of Dietary Supplement Programs in the FDA’s Center for Food Safety and Applied Nutrition. “The FDA is committed to protecting U.S. consumers from products and companies that make unlawful claims to treat or prevent diabetes, and we’ll continue to hold companies accountable by alerting the public about products that place consumers at risk.”

As part of the process, the FDA has requested responses from the companies within 15 working days explaining how they will address issues or provide reasoning and supporting information for why they believed the products are not in violation of the law. Companies that received warning letters included:

This is a breaking news story and will be updated when, and if, more information becomes available.

The FDA and FTC posted warnings to 10 companies for violating the Federal Food, Drug, and Cosmetic Act by selling dietary supplements claiming to cure, treat, mitigate, or prevent diabetes.

FDA Warns 10 Companies For Illegally Marketing Supplements Claiming to Treat Diabetes

With the obesity epidemic projected to grow moving forward, new research from a team of investigators from institutions in Europe is sounding the alarm on the risk of 

becoming overweight or developing obesity

 among different age groups over the next decade.

An analysis of electronic health record (EHR) data from more than 2 million individuals from 400 primary care practices in England from 1998-2016, results indicate the greatest risks for becoming overweight or developing obesity were seen among patients aged 18-24 years and investigators purport these findings should serve as a call for immediate policy changes to address the growing burden of obesity on society.

“Our results show clearly that age is the most important sociodemographic factor for BMI change. Young people aged 18 to 24 have the highest risk of BMI gain, compared to older people. We also found that among individuals with obesity, those aged between 35 and 54 had the highest risk of not losing weight compared to other adults,” said Michail Katsoulis, MSc, a senior research fellow at the University College London (UCL) Institute of Health Informatics, 

With obesity placing an increasing burden on health systems and society as a whole, the current study was conducted with the aim of identifying patient groups at an elevated risk of weight and BMI change through analysis of data from EHRs. To do so, investigators designed their study as a longitudinal, population-based cohort study of patients aged 18-74 years, with BMI and weight measurements recorded from January 1, 1998, and June 30, 2016, and with at least 1 year of follow-up identified from the CALIBER program. A collaborative data-sharing platform, use of the CALIBER program allowed access to EHR data related to 2,092,260 individuals from 400 primary care practices in England meeting eligibility criteria.

With more than 9 million BMI measurements from this patient cohort. Investigators planned to assess longitudinal changes in BMI over 1, 5, and 10 years and calculate absolute risk and odds ratio for transition between BMI groups, which were defined using WHO criteria. Associations with demographics factors were assessed using logistic regression, adjusted for baseline BMI, family history of cardiovascular disease, use of diuretics, and comorbidities.

Results of the investigators' analysis suggested young age adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Specifically, results suggested adults aged 18-24 years had the highest odds (OR, 4.22; 95% 3.86-4.62) and greatest absolute risk (37% vs 24% of transitioning from normal weight to overweight or obesity at 10 years when compared to those aged 65-74 years.

Similarly, adults in the youngest age group with overweight or obesity at baseline were at the greatest risk of transition to a higher BMI category. Specific results highlighted by investigators included the increased OR (4.60; 95% CI, 4.06-5.22) and absolute risk (42% vs 18%) of transition from overweight to class 1 and 2 obesity and increased OR (5.87; 95% CI, 5.23-6.50) and absolute risk (22% vs 5%) of transition from class 1 and 2 obesity to class 3 obesity.

Investigators also noted associations with transitions were consistently, but less strongly observed for other demographics factors. Specifically, increased ORs were observed for transition from normal weight o overweight or obesity at 10 years for men compared to women (OR, 1.12; 95% CI, 1.08-1.16), Black individuals compared to White individuals (OR, 1.13; 95% CI, 1.04-1.24), and those livings in the most socially deprived areas compared to the least deprived areas (OR, 1.23; 95% CI, 1.18-1.27).

“Health systems, like the NHS, need to identify new ways to prevent obesity and its consequences. This study demonstrates that NHS data collected over time in primary care holds an important key to unlocking new insights for public health action,” said Harry Hemingway, MBBS, professor of Clinical Epidemiology at the UCL Institute of Health Informatics, in a statement.

Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records

An analysis of EHR data from more than 2 million patients in England is detailing the increased risk of becoming overweight or developing obesity in the next decade among young adults aged 18-24 compared to adults in other age groups. 

Young Adults at Greatest Risk of Becoming Overweight, Developing Obesity

A man in his mid-60’s with a history of DM and tobacco use presents to the ED for 6 months of right hip and groin pain that initially bothered him only with activity but is now keeping him up at night. He did injure it slightly about 6 months prior when stepping off a curb awkwardly but doesn’t know why it still hurts and is getting worse if it has anything to do with that. He denies any fever, abdominal pain, or other complaints. His doctor is trying to get a spine MRI approved, but the pain has become so bad recently that he cannot even sleep properly.

Vital signs are normal. A physical exam is otherwise normal except for limping during ambulation.

Our latest endocrine case report from Brady Pregerson, MD, features a man in his mid-60s presenting to the emergency department for 6 months of hip and groin pain. Can you determine the correct diagnosis?

Endocrine Case Report: Groin Pain

Data from a meta-analysis of 29 studies suggests the US spent $8 billion on the treatment and diagnosis of 

Published midway through Polycystic Ovary Syndrome Awareness Month, the study builds on previous research suggesting the cost of initial diagnosis and reproductive morbidities cost nearly $4 billion by providing evidence of the additional costs associated with PCOS, such as pregnancy-related and long-term comorbidities, including stroke and 

“Although PCOS affects at least one in seven women and leads to over $8 billion in healthcare costs annually in the United States alone, it is frequently misunderstood or overlooked by clinicians and policymakers,” said lead investigator Carrie Riestenberg, MD, of the University of California, Los Angeles, 

. “With a better understanding of how to diagnose and treat this common condition effectively, we may be able to reduce the economic burden as well as the impact on women’s quality of life.”

With PCOS affecting up to 1-in-5 reproductive-aged women in the US, it is among the most common conditions for female patients. With an interest in building on a previous study, which estimated the economic burden of PCOS to be $2.6 billion in 2004 and $3.7 billion in 2020 after adjusting for inflation, Riestenberg and a team of colleagues designed the current study with the intent of providing a more complete estimate of the annual cost of PCOS in the US. To do so, investigators designed their study as a meta-analysis of data from within the PubMed, EmBase, and Cochrane Library databases with no date restrictions.

For inclusion in the meta-analysis, studies needed to be observational., controlled studies that examined risk of adverse pregnancy outcomes or long-term health outcomes in women with PCOS compared against a control group. Investigators noted studies that reported relative risks, odds ratios, or incidence data were eligible for inclusion but those without a control group, did not match or control for BMI, and those reporting hazard ratios were excluded. Of note, investigators used the NIH diagnostic criteria for PCOS after determining it yielded the most consistent and conservative prevalence estimates and the consumer price index was used to adjust for inflation.

From their search, investigators identified investigates identified a total of 3146 studies for potential inclusion in the study. Of these, 3082 were excluded after abstract screening and 64 were reviewed in detail. Ultimately, 29 studies were included in the meta-analysis.

Using these studies, investigators were able to calculate the prevalence and economic burden associated with various comorbidities and pregnancy-related conditions associated with PCOS, including gestational hypertension, gestational diabetes, preeclampsia, type 2 diabetes mellitus, myocardial infarction, and stroke. From this data, investigators determined the estimated economic burden of managing long-term and pregnancy-related comorbidities with PCOS was $4.3 billion in 2020. When combining this figure with previous estimates of the burden of diagnosis and treatment, investigators estimated the total economic burden of PCOS to be $8 billion annually in 2020.

“Our results suggest that diagnosing PCOS sooner could help reduce the complications women experience and lower the overall cost of providing care,” Riestenberg said. “Increased public awareness of the condition could help improve the quality of care.”

Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences,”

Journal of Clinical Endocrinology & Metabolism.

A meta-analysis builds upon previous research and provides new insight into the total costs of diagnosis and treating PCOS as well as the costs of treating PCOS-related comorbidities. 

Treating Polycystic Ovary Syndrome Costs $8 Billion in US Annually


New research from a trial conducted by investigators at the Cleveland Clinic is underscoring the impact of dietary choices and interventions in reducing cardiovascular risk factors among children with overweight or obesity.

An assessment of 3 specific eating patterns in children aged 9-18 years old with a BMI in the 95th percentile or greater, results of the study provide evidence suggesting adherence to either of the 3 diets examined in the trial could result in significant improvements in cardiovascular risk factors among this patient population.

“This study helps show the importance of starting healthy eating patterns as young as possible. We know that cardiovascular disease begins in childhood, and children's eating patterns are easier to mold than adolescents and adults,” said lead investigator Michael Macknin, MD, professor emeritus of pediatrics of Cleveland Clinic Lerner College of Medicine, in 

With an interest in further exploration of the impact of dietary choices on cardiovascular risk and risk factors among pediatric considered overweight or obese, Macknin and colleagues at the Cleveland Clinic designed the current study as a prospective randomized trial comparing the effects of the American Heart Association Diet, Mediterranean Diet, and a plant-based diet for 52 weeks from patients within the Cleveland Clinic’s Pediatric Obesity Registry. For inclusion in the trial, patients needed be 9-18 years of age, have a BMI for age and sex in the 95th percentile, and a total cholesterol greater than 169 mg/dL.

Ultimately, 96 child-caregiver dyads were identified for inclusion in the trial. Patients included in the study were asked to attend educational sessions to learn more about their assigned diets and receive support. Anthropometric measurements, including weight, BMI, blood pressure, and waist circumference, were recorded at weeks 0, 4, and 52. Investigators used fasting blood tests to assess biomarkers of risk including total cholesterol, LDL-C, HDL-C, and hsCRP.

Each of the 3 study arms contained 32 children and 32 parents or guardians. Of these 96 dyads, 83% attended the first study visit, 70% attended the 4-week visit, and 33% completed the 52-week visit. Investigators pointed out the small sample sizes resulted in inadequate power to detect significant differences in study results associated with participation in education sessions and study visits.

Upon analysis, results suggested significant improvements were observed in all groups at 4 weeks when examining weight, systolic and diastolic blood pressure, and myeloperoxidase. Additionally, similar statistically significant results were observed for total cholesterol and LDL-C. When assessing reasons for opting not to enroll in the study, time was identified as the only significant deterrent (

“Because the process of heart disease begins in childhood, prevention should begin there as well,” said W.H. Wilson Tang, MD, study author and research director in the section of heart failure and cardiac transplantation medicine in the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. “A large majority of heart disease is due to modifiable or controllable risk factors, so it’s important for children to understand that they are in large part responsible for their health.”

Three Healthy Eating Patterns and Cardiovascular Disease Risk Markers in 9 to 18 Year Olds With Body Mass Index >95%: A Randomized Trial

A Cleveland Clinic trial assessing the effects of 3 healthy eating patterns in children with overweight or obesity details the improvements in cardiovascular risk factors seen with adherence to a healthy eating pattern. 

Trial Results Suggest Healthy Eating Patterns Could Reduce Cardiovascular Risk in Pediatric Patients

The US Food and Drug Administration has approved ranibizumab-nuna (BYOOVIZ, SB11) for the treatment of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, and myopic choroidal neovascularization.

The approval of the ranibizumab (LUCENTIS) biosimilar was announced in a statement on September 20 and was granted to Samsung Bioepis Co., Ltd. and Biogen Inc.

This approval marked the first ophthalmology biosimilar to become FDA approved in the United States.

According to the FDA, biosimilar products show similar efficacy and safety as the reference product, with savings in the US over the next 5 years projected to exceed $100 billion.

Ranibizuman is an anti-vascular endothelial growth factor (VEGF) therapy that prevents vision loss in patients with retinal vascular disorders that can cause irreversible blindness or visual impairment in adults.

The agent is administered by intravitreal injection once a month. Potential serious side effects including endophthalmitis and retinal detachment, increase in intraocular pressure, and thromboembolic events.

The approval was based on a randomized, Phase 3 study of SB11, in which the efficacy, safety, pharmacokinetics, and immunogenicity of SB11 was compared to reference ranibizumab in patients with wet AMD.

A total of 705 patients were randomized 1:1 to either SB 11 or reference ranibizumab with monthly injections (0.5 mg), with 634 patients receiving treatment until week 48.

Data show the least-squares mean change in best-corrected visual acuity from baseline at week 52 was 9.79 letters for SB11. In comparison, data show 10.41 letters for reference ranibizumab (difference -0.62; 90% CI, -2.092 to 0.857).

In addition, the LS mean change in central subfield thickness −139.55 μm for SB11 vs −124.46 μm for reference ranibizumab (difference -15.09; 95% CI, -25.617 to -4.563).

According to investigators, treatment-emergent adverse events and immunogenicity profile of both products were comparable at all time points up to week 52.

, Kyung-Ah Kim, Senior Vice President and Development Division Leader, Samsung Biopis, noted the milestone for the nearly 11 million people in the US who are affected by age-related macular degeneration.

“The approval of BYOOVIZ™ underscores our continued commitment to providing valuable treatment options for people who do not have access to life-enhancing biologic medicines around the world,” she said.

Further, Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars, FDA Center for Drug Evaluation and Research, 

 that the approval marked a step forward in the FDA’s commitment to provide access to safe and effective biological products.

“Continuing to grow the number of biosimilar approvals is a key part of our efforts to provide greater access to treatment options for patients, increase competition and potentially lower costs,” Yim said.

Previously, the agent was approved in Europe and the United Kingdom in August 2021. It is the fifth biosimilar granted to Samsung Bioepis in the United States, with the others including infliximab (Renflexis), trastuzumab (Ontruzant), etanercept (Eticovo), and adalimumab (Hadlima).

The approval, which was announced in a statement on September 20, makes Byooviz (ranibizumab-nuna) the first biosimilar to Lucentis (ranibizumab injection) for the treatment of several eye diseases and conditions.

FDA Approves Byooviz, First Biosimilar to Treat Macular Edema and Other Eye Conditions

In response to the growing obesity epidemic, the American Heart Association (AHA) has released guidance in the form of a scientific statement outlining 

With data suggesting more than 100 million in the US have hypertension, the scientific statement outlines the need for effective, long-term solutions to weight loss to maintain reductions in hypertension and also calls for clinicians to consider other avenues outside of lifestyle modification for weight loss, such as medications and metabolic surgery.

“Weight loss achieved through dietary changes and increased physical activity are the cornerstones of treatment for high blood pressure that’s related to being overweight. However, these lifestyle behaviors are often not sustained over the long term. Subsequently, reductions in blood pressure aren’t maintained over time,” said Chair of the statement writing group Michael E. Hall, MD, MS, FAHA, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson, Mississippi, in 

. “The new scientific statement suggests medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity.”

The AHA’s scientific statement, which is 13 pages in length and contains nearly 100 references, opens by providing clinicians with an overview of epidemiology and pathophysiology of obesity hypertension before diving into avenues for reducing body weight, including lifestyle modification, pharmacotherapy, and bariatric procedures. Underlining the AHA’s stance from their June 2021 statement, the present statement, which was prepared on behalf of the AHA’s Council on Hypertension, the Council on Arteriosclerosis, Thrombosis, and Vascular Biology, the Council on Lifestyle and Cardiometabolic Health, and the Stroke Council, outlines the importance of dietary interventions and physical activity as first-line treatment for weight loss and hypertension control, but investigators were quick to point out these changes can be difficult to maintain long-term and can lead to recurrent increases in hypertension.

“There’s no doubt that eating healthy foods has beneficial effects on both weight and blood pressure,” Hall explained. “Numerous weight-loss diets are often successful in the short term; however, eating healthy foods consistently and long term, and maintaining weight loss are challenging.”

The next portion of the statement called for an increase in consideration of pharmacologic therapies for obesity hypertension, if lifestyle modifications have proven unsuccessful in achieving weight reduction and blood pressure control. In addition to FDA approved therapies for long-term weight loss, authors highlight the latest revelations related to the potential for reductions in body weight and blood pressure seen with GLP-1 receptor agonists. Specifically, liraglutide and once-weekly semaglutide 2.4 mg, which was not yet approved at the time of writing, were highlighted by statement authors.

“We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke. However, we may be able to prevent these complications. When combined with lifestyle changes, anti-obesity medicines and surgical procedures can be effective long-term solutions for weight loss and blood pressure control in select individuals who are overweight or have obesity,” Hall added.

The last treatment approach discussed within the statement highlighted surgery for weight loss. Although considered a newer approach to mitigating the effects of obesity, authors point out the popularity and safety of these procedures have grown in recent years. According to the statement, more than 215,000 metabolic procedures were performed in 2016, with the most popular being sleeve gastrectomy followed by Roux-en-Y gastric bypass. With these types of procedures typically reserved for candidates with a BMI at or equal to 35 kg/m2, investigators point out observational data suggests bariatric procedures could contribute tor solution of hypertension in 63% of procedures. Additionally, authors highlight the contributions of the GATEWAY trial, as it is the only controlled trial involved metabolic surgery with blood pressure as a primary end point, to our current understanding of the effects of metabolic surgery. In that trial, patients were 6 times more likely to experience resolution of hypertension with metabolic surgery than they were with standard medical therapy.

“Metabolic surgery techniques are continuing to evolve, and they are getting less invasive and less risky,” Hall said. “For select individuals, medications or metabolic surgery or both may be considered in addition to healthy diet and increased physical activity.”

Before the conclusion of their statement, authors highlighted what they perceive as areas in need of further research related to obesity hypertension. Specific research recommendations included the need for more randomized trials in the space, research into the mechanisms of obesity-related diseases, and the need for a greater understanding of the long-term safety and efficacy of various treatment and prevention strategies.

“There are still many unanswered questions and many opportunities for research that can help people live healthier, longer,” Hall added.

Weight-Loss Strategies for Prevention and Treatment of Hypertension,

Released on September 20, the latest scientific statement from the AHA outlines potential strategies, including lifestyle modifications, pharmacologic therapies, and weight loss surgery, for the prevention and treatment of obesity hypertension. 

AHA Outlines Weight Loss Strategies for Preventing Obesity Hypertension


The American Diabetes Association (ADA) Standards of Medical Care, received updates this year that reflect the increasingly comprehensive care provided by SGLT-2 inhibitors and GLP-1 agonists, but as Jennifer Green, MD, explained at the 5th Heart in Diabetes meeting, they still require a greater adoption by all relevant prescribers in the US.

In a presentation at The Metabolic Institute of America’s (TMIOA) 2021 Heart in Diabetes sessions in New York, NY this weekend, Green, a professor of medicine at Duke University Medical Center’s Division of Endocrinology, Metabolism and Nutrition, highlighted key 2020 additions to the ADA Standards of Medical Care document—headlined by the strengthened advocacy of SGLT2 inhibitor and GLP-1 agonist use in high-risk patients with type 2 diabetes (T2D), regardless of their glucose-lowering needs and metformin use.

Though metformin remains the recommended initial pharmacologic agent for T2D, early combination therapy with an evidenced agent should be considered for severely hyperglycemic patients.

Other high-risk categories were better defined for providers treating T2D who may be adding SGLT2 inhibitors or GLP-1 agonists: atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or chronic kidney disease (CKD). Though previous guidance have recommended combination therapy for patients at such risk, few had stratified the risks in such a way. As Green said, “We tried to be a little more directive.”

The 2021 updates also provided guidance for initiating SGLT2 inhibitors in patients with T2D who don’t have HF but may nonetheless benefit from the drug class’ risk-reducing properties, with Green noting these patients “now have a home” in guideline categorization.

SGLT2 inhibitors or GLP-1 agonists are now recommended in:

Patients with T2D who have established ASCVD or kidney disease, to reduce comprehensive cardiovascular disease risk and manage glucose levels.

Patients with T2D who have established ASCVD, multiple risk factors for ASCVD or diabetic kidney disease, for reduced risk of major adverse cardiovascular events (MACE) or HF hospitalization.

As Green noted, patients with ASCVD and/or CKD may be progressed toward the recommended regimen differently, but the intent remains the same.

These new recommendations would implicate a significantly greater rate of US patients being eligible for multi-drug management of T2D and concurrent disease risks than is currently being actually treated. Green cited Duke colleagues’ assessment of the 2021 ADA guideline updates, as applied to a primary care electronic health record database. The findings identified approximately one-third of all observed primary care patients with T2D met criteria for SGLT2 inhibitor and GLP-1 agonist use based on the recommendations.

“That is an enormous percentage and an enormous number if applied to the entire country,” Green said.

However, real-world application paces significantly behind. A query of pharmacy and medical claims data from within Anthem identified 155,958 patients with T2D and established ASCVD. Duke investigators sought the proportion of such patients to treat their disease with any of the following regimen: high-intensity stain, ACE inhibitors or angiotensin receptor blockers, and SGLT2 inhibitors or GLP-1 agonists.

They found that 37.4% of patients were on none, 40.7% were on 1 therapy, 19.4% were on 2, and just 2.7% on all 3. Among patients prescribed SGLT2 inhibitors or GLP-1 agonists, a significant proportion were at lower risk of cardiovascular or renal outcomes than other eligible patients, Green noted.

Green stressed in her presentation that this data were US-based, insured patients who would have fewer barriers to high-cost regimens than others. She concluded her presentation with a call for “more overlap and shared responsibility” of stakeholders impacted by these guideline updates: primary care physicians, diabetologists, and cardiologists.

“Many people have clear indications for these newer drugs, but implementation remains inadequate, and there’s quite a lot of work to be done,” she said.

The Standards of Medical Care in Diabetes—2021 guideline and resources are available to view here.

Jennifer Green, MD, explains how delays in the adoption of new guideline recommendations are holding back optimal management of type 2 diabetes in the US. 

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