Coverage of the Endocrine Society's 2021 Annual Meeting

ENDO 2021

Data from a study conducted by clinicians at the University of Maryland School of Medicine is offering insight into trends of SGLT2 inhibitor prescribing in patients with diabetes and heart failure at medical centers in the US.

Presented at the American Academy of Clinical Endocrinology’s 30th Annual Meeting 

, the retrospective chart review suggested fewer than 10% of eligible patients with type 2 diabetes and heart failure received a prescription for an agent within the class and also indicated rates of discontinuation were greater than 40% among those who initiated therapy with an SGLT2 inhibitor.

“Sodium-glucose cotransporter-2 inhibitors are under prescribed, reaching only 9.6% of the ideal patient population—those with diabetes mellitus and heart failure even in a tertiary care diabetes center of excellence,” wrote investigators.

Led by Megan Kristan, MD, a fellow in the Division of Endocrinology at the University of Maryland Medical Center, and a team of colleagues, the current study was designed with an interest in describing current trends in SGLT2 inhibitor prescribing among patients with type 2 diabetes and heart failure. For the purpose of analysis, investigators designed their study as a retrospective cohort review of patients treated at an academic tertiary center between January 1, 2015, and February 5, 2021.

For inclusion in the analysis, patients needed to be diagnosed with diabetes and congestive heart failure. Patients were excluded if they were missing data related to demographic information or clinic data such as type of SGLT2 inhibitor prescribed, A1c, and time to discontinuation.

In total, 1340 patients were identified by investigators for inclusion. This cohort had a mean age of 63.8±12.3 years, 55.2% were women, and 79.1% were non-Hispanic Black. Investigators also noted 27.5% of the cohort was commercially insured and 54.2% were insured through Medicare. Overall, just 129 (9.6%) of the 1340 patients were prescribed an SGLT2 inhibitor and, among these, 54 (42.9%) discontinued use during the study period.

When compared to those who did not receive a prescription, those who received a prescription for SGLT2 inhibitors were younger, more likely to have commercial insurance (42.6% vs 25.8%), and more likely to identify as non-Hispanic White (26.4% vs 16.2%). When assessing those who received a prescription for an SGLT2 inhibitor, results suggested the mean time to discontinuation was 1.5 months and those who were started on canagliflozin were more likely to discontinue than those prescribed to any other SGKT inhibitor (46.3% vs 8.3%).

Investigators noted there were no significant differences in discontinuation of SGLT2 inhibitor therapy based on demographic differences among patients included in the study. Investigators also pointed out no difference in adverse event rates was seen prior to or after beginning treatment with SGLT2 inhibitors.

“Those patients that were prescribed SGLT2 inhibitors were more likely to be young and have commercial insurance. A trend towards significance was seen with race, more commonly prescribed in White patients than those of racial/ethnic minorities. Attention to prescribing practices can help to minimize these differences,” wrote investigators.

SGLT-2 Inhibitor Prescribing Patterns at Tertiary Care Diabetes Center for Individuals with Diabetes and Heart Failure,

Articles

Data from a retrospective review of patients with type 2 diabetes and heart failure at a diabetes center in Maryland details trends in prescribing and discontinuation in a real-world setting over a 5-year period. 

AACE 2021 Study Details SGLT2 Inhibitor Trends in US Diabetes Center

New research presented at the American Academy of Clinical Endocrinology’s 30th Annual Meeting (AACE 2021) is detailing the effect of Medtronic’s MiniMed 670G system on change in HbA1c and time in range in patients with type 1 diabetes.

A systematic review and meta-analysis of data from major databases included a dozen studies and determined Auto Mode use results in an A1c change of -0.5% and a nearly 10% increase in time in range.

“This meta-analysis of MiniMed™ 670G Auto Mode therapy use compared with other therapies showed a significant improvement in glycemic control. These comprehensive findings demonstrate a safe and clinically meaningful impact of a first-of-its-kind device for T1D management,” wrote investigators.

With approval coming from the US Food and Drug Administration in 2016, the MiniMed 670G system became the first hybrid closed-loop insulin delivery system approved anywhere in the world. Designed for use in patients with type 1 diabetes, the device represented a revolution in care and has found its way into the care of many with type 1 diabetes.

Presented at AACE 2021 by Toni Cordero, PhD, of Medtronic, the current study was designed as a systematic review and meta-analysis of trials examining use of the MiniMed 670G Auto Mode therapy versus a comparator for effect on A1c and time in range. Performing a search of the Embase, PubMed, and Web of Science databases returned 127 articles, of which 12 met the investigators’ inclusion criteria.

Of the 12 trials identified for inclusion, all 12 reported on change in A1c, 11 reported data on time in range, and 9 reported on time below range. Additionally, investigators noted 10 trials investigated the MiniMed 670G in Auto Mode versus open-loop Manual Mode therapy, one assessed Auto Mode against multiple daily injections with CGM, and another compared Auto Mode versus sensor-augmented pump therapy.

Upon analysis, results indicated there was a significant reduction in mean difference in A1c (MD, -0.50; 95% CI, -0.59 to -0.42) between the pre- and post-Auto Mode intervention and significant heterogeneity was also noted (

2=70%). Investigators noted a significant gain in time in range between the pre- and post-Auto Mode intervention, with significant heterogeneity in study estimates. Additionally, investigators also pointed there was a significant reduction in time blow range (MD, -0.21; 95% CI, -0.33 to -0.10) and significant heterogeneity was observed in study estimates (

“Analysis demonstrated a reduction in A1C and an increase in TIR with Auto Mode use, suggesting a benefit in terms of glycemic control. Significant variation in reported estimates, likely due to differing protocols across the various studies, indicate that a more standardized protocol for closed-loop system trials may reduce heterogeneity,” wrote investigators.

Systematic review and meta-analysis of MiniMed™ 670G system therapy on change in A1C and time spent in target glucose range,

A systematic review and meta-analysis of a dozen trials assessing the MiniMed 670G system provides insight into the effects of the hybrid closed-loop system on A1c and time in range among patients with type 1 diabetes.

Analysis Demonstrates MiniMed 670G System Helps Improve A1c and Time in Range in Type 1 Diabetes

The US Preventive Services Task Force (USPSTF) has issued a recommendation on counseling women about healthy weight and weight gain during pregnancy.

Journal of the American Medical Association, 

the USPSTF recommendation statement advises clinicians to offer effective counseling programs to help pregnant people maintain a healthy amount of weight and prevent excess weight gain in pregnancy would provide a moderate net benefit to this patient population. The first time the USPSTF has made such a recommendation, it was awarded a grade of B, which indicates moderate certainty.

"Healthy weight gain during pregnancy lowers the risk for gestational diabetes, babies born with a high birth weight, and emergency cesarean sections,” said Task Force member Chien-Wen Tseng, MD, MPH, Professor and Research Director in the Department of Family Medicine and Community Health at the University of Hawaii John A. Burns School of Medicine, in 

. “There are many effective counseling interventions that can help, so clinicians should work with their patients to identify the best fit.”

With the impact of obesity, gestational diabetes, and other comorbidities among pregnant woman defined in previous research, the USPSTF sought to provide guidance to clinicians in hopes of minimizing the detrimental of excess weight gain during pregnancy. In the statement published in 

the Task Force detailed the importance of this new recommendation as well as additional details related to their rationale, assessments of potential harm and effectiveness, and supporting evidence for the recommendation.

Within the statement, the Task Force noted counseling intervention should focus on topics including nutrition, physical activity, and lifestyle or behavior changes. The statement advocated for multicomponent interventions, such as active/supervised exercise or counseling on diet and activity. The recommendation noted these interventions could be delivered using a collaborative approach to care that could include clinicians, dietitians, qualified fitness specialists, physiotherapists, and health coaches. The Task Force also pointed out these interventions could be delivered in individual or group settings as well as through traditional in-person or telehealth mediums.

Summary Data Review

This recommendation statement, titled “

Behavioral Counseling Interventions for Healthy Weight and Weight Gain in Pregnancy US Preventive Services Task Force Recommendation Statement

The USPSTF has issued the organization's first recommendation on interventions for promoting healthy weight gain during pregnancy and also provided an overview of the evidence base used for the recommendation statement.

USPSTF Issues Recommendation on Interventions for Healthy Weight Gain During Pregnancy

A long-term study of nearly 400 women from Finland is shedding light on the predictive value of autoantibodies in progression to type 1 and type 2 diabetes after gestational diabetes.

Results of the 23-year study, which were presented at the 23rd European Congress of Endocrinology (e-ECE 2021), indicate women who experience gestational diabetes were more likely to develop type 1 and type 2 diabetes later in life and suggests testing for glutamic acid decarboxylase and islet cell autoantibodies could help identify women at increased risk of type 1 diabetes.

“The strong relationship between women who have gestational diabetes and women who experience type-1 and type-2 diabetes later in life, suggests that women should now receive more extensive testing during pregnancy, in order to determine their level of risk,” said Kaisu Luiro, MD, PhD, of the University of Helsinki,

 “We also hope that healthcare professionals initiate conversations with their patients about the relationship between GDM and diabetes later in life. In the future, there are on-going developments for more accurate prediction models which hope to give a more specific suggestion as to who should be tested during pregnancy.”

To build on previous research, Luiro and a team of colleagues designed the current study as an analysis of data from a prospective cohort study of 391 women with gestational diabetes and 391 age-, parity- and delivery date-matched controls who delivered from 1984-1994. Hoping to learn more about the presence of autoantibodies and the development of type 1 and type 2 diabetes, investigators assessed presence of 4 autoantibodies using first trimester samples from women included in the study and assessed diabetes status through follow-up questionnaires sent from 2012-2013.

Autoantibodies of interest for the study included islet cell (ICA), glutamic acid decarboxylase (GADAs), insulin (IAA), and insulinoma-associated antigen 2 autoantibodies (IA2A). Investigators noted the mean follow-up time of patients within the study was 23.1 (18.7-28.8) years.

Upon analysis, results indicated single autoantibody positivity was detected among 12% (n=41) of the gestational diabetes cohort and among 2.3% (n=8) of the control cohort. Further analysis indicated 2.6% and 2.3% of the gestational diabetes cohort tested positive for 2 and 3 autoantibodies, respectively. In comparison, only a single patient from the control cohort had 2 autoantibodies detected.

Among the gestational diabetes cohort, ICA positivity was observed in 12.5%, GADA positivity was observed in 6.0%, IA2A positivity was observed in 4.9%, and IAA positivity was observed in 1.2%. In contrast, among those in the control cohort, GADA positivity was observed in 1.4%, IA2A was observed in 0.8%, IAA positivity was observed in 0.6%, and ICA positivity was observed in 0.3%.

Investigators noted detection of ICA, GADA, and IA2A autoantibodies were associated with decreased type 1 diabetes mellitus-free survival time and time to diagnosis. Furthermore, all patients testing positive for 3 autoantibodies developed type 1 diabetes mellitus within 7 years of having gestational diabetes, but the development of type 2 diabetes following gestational diabetes occurred independently of autoantibody positivity.

Autoantibodies in prediction of diabetes after gestational diabetes—a 23-year prospective cohort study,

A 23-year study suggests presence of autoantibodies could aid clinicians in predicting the risk of developing type 1 diabetes among women with gestational diabetes.

Autoantibody Testing Could Identify Women at Increased Risk of Type 1 Diabetes Following Pregnancy

New research suggests a low calorie ketogenic diet could help improve body weight and testosterone levels in men who are overweight.

Presented at the 23rd European Congress of Endocrinology (e-ECE 2021), the single-arm study found implementing a very-low calorie ketogenic diet was associated with increased total testosterone levels, especially in patients who were insulin-sensitive, after just 4 weeks.

“We aimed to evaluate the response of total testosterone and sex hormone levels to a very-low calorie ketogenic diet in a cohort of overweight or obese non-diabetic male subjects and what we found was that there is a noticeable relation between a specific, controlled diet and insulin action, energy balance, and testicular function,” said Angelo Cignarelli, MD, PhD, assistant professor at the University of Bari in Italy, 

With the prevalence of obesity exploding in recent decades and rates expected to continue rising, new emphasis has been placed on the impact of nutrition among people with overweight or obesity. To learn more about the effects of certain dietary approaches on health, Cignarelli and colleagues from the University of Bari designed the current study as a single-arm, uncontrolled study assessing the impact of a 4-week, low-calorie ketogenic diet on body weight, fat mass, BMI, and sex hormone levels in 17 men considered to be overweight or obese.

At baseline, the mean age of the cohort was 41.3 (SD, 12.2) years, the mean BMI was 36.4 (SD, 5.2) kg/m2, and the mean TT was 2.5 (SD, 1.0) ng/ml. Of note, the very-low calorie ketogenic diet used in the study advised patients to reduce their daily calorie intake to less than 800.

All patients included in the study were advised to follow this diet and underwent assessments of anthropometric parameters, oral glucose tolerance testing (OGTT), bioelectrical impedance analysis, and blood testing for the measurement of glycemia, insulin, total testosterone (TT), sex hormone binding globulin (SHBG), and luteinizing hormone (LH) performed before and after 1 and 4 weeks of very-low calorie ketogenic diet.

Upon analysis, investigators found use of a very-low calorie ketogenic diet was associated with significant reductions in body weight (-9.3 [SD, 1.8] kg), fat mass (-6.5 [SD, 2.1] kg), and BMI (-3.1 [SD, 0.7]). Additionally, results indicated a mean loss of 14.9±3.9% of initial body weight was achieved among the study population at 4 weeks.

When assessing serum TT levels, a very-low calorie ketogenic diet was associated with significant increased after 1 (0.49 [SD, 0.59] ng/ml) and 4 weeks (0.89 [SD, 0.91] ng/ml). Further analysis indicated a similar trend for serum SBHG levels after 1 (3.47 [SD, 4.73] nmol/l) and 4 weeks (10.94 [SD, 12.87] nmol/l) of very-low calorie ketogenic diet.

Investigators noted additional analyses stratifying patients according to high and low responders based on TT variations after 1 week indicated responders differed only by level of insulin sensitivity. Investigators also pointed out low responders displayed a significantly high level of insulinemia compared to those considered high responders.

Investigators noted the design of their study limitations the applicability of results and called for further research into the effects of a very-low calorie ketogenic diet on additional clinical outcomes.

Effects of a very low-calorie ketogenic diet on androgen levels in overweight/obese men: a single-arm uncontrolled study

A single-arm study examining the effects of a very-low calorie ketogenic diet over a 1-month period indicates the dietary approach was associated with improvements in body weight and sex hormones among men with overweight or obesity. 

Single-Arm Study Finds Very-Low Calorie Ketogenic Diet Could Improve Testosterone Levels in Men

A new study assessing the impact of social isolation and loneliness is underlining the increased risk of cardiovascular disease associated with increased isolation and loneliness among 

The study, which assessed data from Women’s Health Initiative (WHI), evaluated nearly 60,000 without a history of cardiovascular events and found 

 was 16% greater among those with high levels of social isolation, 11% greater in those with high levels of loneliness, and 29% greater in those reporting both.

“People who experience social isolation or loneliness tend to withdraw and don’t engage often in healthy behaviors, which may become a cyclical pattern. Over time, the unhealthy behaviors coupled with social isolation and feeling lonely put them at an increased risk for cardiovascular disease,” Natalie Golaszewski, PhD, a postdoctoral fellow at the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego, 

Funded by the National Institute of Aging of the National Institutes of Health, the current study provides new insight into the relationship between social well-being and risk of cardiovascular disease at a time when reports of social isolation and loneliness are at an all-time high as a result of the pandemic. Investigators designed their study to use information from women in the WHI who were free from cardiovascular disease at baseline and had complete information related to assessments of social activities, living status, marital status, loneliness, and social support from 2014-2015.

Of note, loneliness was assessed using the 3-item UCLA Loneliness Scale and social isolation was assessed using an index scored derbies from questions related to personal relationships and social activities.

A cohort of 57,825 women, with a mean age of 79±6 years and follow-up of up to 4 years, was identified for inclusion. For the purpose of analysis, the primary outcome of interest for the study was major cardiovascular disease, which investigators defined as myocardial infarction, stroke, and cardiovascular disease death. Investigators noted hazard ratios for risk were estimated for 1-IQR increment in isolation and loneliness using 3 progressively adjusted Cox proportional hazard models.

Over 186,762 person-years of follow-up, 1599 incident major cardiovascular disease events were identified by investigators. In fully adjusted models, results indicated each 1-IQR increment in social isolation and loneliness increased cardiovascular disease risk by 7% (HR, 1.07; 95% CI, 1.03-1.12) and 5% (HR, 1.05; 95% CI, 1.01-1.09), respectively. Investigators pointed out further analysis revealed the presence of social support did not appear to be a modifier of either association (


“Our results suggest measures of social isolation and loneliness, even with brief questions, should be incorporated into standard care,” Golaszewski said. “We monitor our patients’ blood pressure, weight and temperature, and it might also be beneficial to capture the social needs that women may be lacking — to better understand cardiovascular risk and develop solutions.”

Social Isolation, Loneliness, And Cardiovascular Disease Among Older Women In The Women’s Health Initiative

,” was presented at the AHA EPI Lifestyle Conference 2021.

An analysis of WHI data indicates social isolation and loneliness were associated with significant increases in risk of major cardiovascular disease, even after adjustment for other clinical risk factors. 

Loneliness, Social Isolation Tied to Increased Risk of Cardiovascular Disease in Postmenopausal Women

New research from the University of Utah suggests undergoing gender-affirming hormone therapy may not increase cardiovascular disease risk among transgender patients.

A retrospective chart review of 50 trans female and 50 trans male patients, results suggest an increased presence of risk factors at baseline could be driving the increased risk of atherosclerotic cardiovascular disease (ASCVD) seen among this patient population, but also indicate hormone therapy may have a negative impact on some ASCVD risk factors in trans male patients.

“Gender-affirming hormone therapy appears to have greater benefits than risks for transgender adolescents and young adults,” said lead investigator Nicole L. Mihalopoulos, MD, MPH, chief of the division of adolescent medicine at the University of Utah, 

. “For some people, these findings influence their decision to not to start gender-affirming hormones during adolescence. However, without gender-affirming hormone therapy, transgender individuals may experience worse gender dysphoria, depression, anxiety and possibly increased suicidal ideations.”

With previous observational data suggesting gender-affirming hormone therapy was associated with increased risk of cardiovascular disease in transgender patients, investigators sought to fill the knowledge gap related to this potential increase in risk. To do so, they designed the current study as a retrospective chart review of patients receiving gender-affirming hormone at the Adolescent Medicine Clinic at Primary Children’s Hospital in Salt Lake City from January 2015-December 2020.

The investigators' initial search returned a population of 300 transgender adolescents. Of these, 100 patients—50 trans female and 50 trans male—were randomly selected for inclusion in the final analyses. For the purpose of analysis, investigators assessed ASCVD risk parameters among these patients at baseline and 1 year after initiating hormone therapy.

Analysis of baseline data indicated at least one abnormal value was found among 50% of trans female and 66% of trans male patients. Investigators pointed out obesity was the abnormal value in 5 of the 25 trans female patients and 13 of the 33 trans male patients with an abnormal value for an ASCVD risk parameter at baseline.

At 1 year, at least one abnormal value was found among 30% of trans female patients and 70% of trans male patients. In paired t-tests, investigators found no significant change in ASCVD risk factors among trans female patients but noted a significant decrease in HDL and a significant increase in BMI among trans male patients.

Investigators noted multiple limitations within their study for clinicians to consider before overinterpretation of results. These limitations included the small sample size, most patients identifying as non-Hispanic White individuals, and limited follow-up period. Investigators also noted the need for future research to further understand the relationship between gender-affirming hormone therapy and ASCVD risk factors.

Transgender Adolescents Have High Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors Before and After Taking Hormone Therapy For 1 Year,

” was presented at the AHA EPI Lifestyle Conference 2021.

A retrospective review of ASCVD risk factors at baseline and 1 year after initiating hormone therapy among transgender adolescents suggests the increased risk of cardiovascular disease seen among this population could be driven by increased prevalence of baseline risk factors.

Baseline Risk Factors Contribute to Increased ASCVD Risk in Transgender Adolescents on Hormone Therapy

An analysis of data from the Lifetime Risk Pooling Project details the increased lifetime risk of coronary heart disease (CHD) associated with 

Presented at the American Heart Association’s Epidemiology, Prevention, Lifestyle and Cardiometabolic Health Conference 2021, results of the analysis suggest premature natural menopause was associated with a 40% greater risk of CHD and also shed light on disparities in incidence of premature menopause among women of different racial/ethnic backgrounds.

“These results indicate premature menopause is associated with higher lifetime risk of coronary heart disease. To mitigate this risk, clinicians need to start asking women about their menopause status earlier,” said Priya Freaney, MD, a cardiology fellow at Northwestern University’s Feinberg School of Medicine, 

. “If a woman experiences menopause before the age of 40, she should let her doctor know so they can be more proactive about optimizing her cardiovascular health—such as weight management and blood pressure—throughout her mid-life years and preventing heart disease over the course of her lifetime.”

With the 2019 AHA/ACC Primary Prevention Guidelines highlighting women who enter menopause before the age of 40 as being at risk for CHD, Freaney and a team of colleagues sought to explore race-specific prevalence of premature menopause and lifetime risk of CHD with the aim of improving risk stratification and prevention. Using pooled data from 6 cohorts within the Lifetime Risk Pooling Project, investigators obtained data related to a cohort of more than 10,000 women between 55-69 years of age with no history of CHD at baseline.

The earliest enrollment among women in the cohort began in 1964 and the latest follow-up date occurred in 2017. Of note, women who underwent surgical menopause were not included in the study. For the purpose of analysis, investigators used modified Kaplan Meier analysis and competing Cox models to estimate for risk for CHD or non-CV death with adjustment for clinical risk factors, such as age, smoking status, obesity, and presence of other comorbidities.

Of the 10,036 individuals identified for inclusion, 3522 were Black and 6514 were White—the mean age of these groups was 61.2±4.3 and 60.0±4.4 years, respectively.

Initial analysis indicated premature menopause was more common among Black women (15.5%) than White women (4.8%). Adjusted analyses indicated the lifetime risk of CHD morbidity and mortality was 41% (HR, 1.41; 95% CI, 1.04-1.90) greater in Black women and 39% (HR, 1.39; 95% CI, 1.03-1.87) greater in White women with premature menopause compared to their counterparts without premature menopause.

“We need to better understand what factors contribute to a woman’s lifetime risk of heart disease, and specifically, how timing of menopause may be connected to risk,” Freaney said.

Association Between Premature Menopause And Lifetime Risk Of Coronary Heart Disease: Lifetime Risk Pooling Project

,” was presented at AHA EPI Lifestyle Conference 2021.

Pooled data from 10k women in the Lifetime Risk Pooling Project suggests premature menopause was associated with a 40% increase in risk of coronary heart disease. 

Premature Menopause Linked to Increased Risk of Coronary Heart Disease

This article was originally published on 

An analysis of the FIDELIO-DKD trial indicates finerenone use could reduce the risk of atrial fibrillation (AF) among patients with type 2 diabetes and chronic kidney disease (CKD).

American College of Cardiology’s 70th Annual Scientific Session (ACC.21)

, results of the analysis indicate use of the nonsteroidal, selective mineralocorticoid receptor antagonist was associated with a 29% reduction in risk of AF among patients in the trial.

“Preventing or delaying the onset of atrial fibrillation in patients with chronic kidney disease and diabetes is particularly important since having atrial fibrillation can worsen chronic kidney disease and having diabetes can worsen atrial fibrillation symptoms,” said lead investigator Gerasimos Filippatos, MD, of the National and Kapodistrian University of Athens, School of Medicine and Attikon University Hospital in Athens, Greece, 

. “Treatment in these patients can also be challenging because they are prone to developing blood clots and bleeding. Finerenone has the potential to reduce the burden of atrial fibrillation in these patients.”

 and suggested use of finerenone was associated with lowered risk of CKD progression and risk of the study’s cardiovascular outcome, finerenone was thrust into the spotlight as clinicians waited to learn more about the agent. The current analysis sought to provide further insight into the effect on new-onset AF as well as the impact of AF history on primary outcomes from the trial.

Briefly, the original FIDELIO-DKD trial randomized more than 5500 patients in a 1:1 ratio to either finerenone or placebo. For inclusion in the trial, patients needed to have a UACR of 30-5000 mg/g, an eGFR of 25-75 mL/min/1.73m2, and be receiving optimal medical therapy with RAAS inhibitors. The trial concluded finerenone use was associated with an 18% reduction in risk for progression of CKD and a 16% reduction in the composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.

The ACC.21 analysis included 5674 patients, including 461 (8.1%) with a history of AF or flutter (AFF). Investigators pointed out patients with a history of AF or flutter are more likely to be male, older, White, and use diuretics and beta-blockers at baseline than those with no history of AFF.

Results of the analysis indicated new-onset AFF occurred among 3.2% of patients on finerenone and 4.5% of patients receiving placebo, which correlates to an incidence rate per 100 patient-years of 1.20 and 1.72, respectively. (HR, 0.71; 95% CI, 0.53-0.94; 

=.0164). Further analysis indicated this risk of new-onset AFF was not modified by age, sex, kidney function, blood pressure, BMI, HbA1c, or use of glucose-lowering therapies.

Additionally, analyses assessing the effect of finerenone on the primary and secondary outcomes from FIDELIO-DKD based on history of AFF at baseline suggested the benefits of finerenone were consistent regardless of baseline history.

“The previously-reported kidney and heart protection with finerenone applied equally to patients with and without pre-existing atrial fibrillation,” Filippatos said.

Finerenone Reduces Onset of Atrial Fibrillation in Patients with Chronic Kidney Disease and Type 2 Diabetes

,” was presented at ACC.21 and simultaneously published in the 

Journal of the American College of Cardiology.

Analysis of data from the FIDELIO-DKD trial suggests use of finerenone was associated with a nearly 30% reduction in new-onset atrial fibrillation among patients within the phase 3 trial. 

Finerenone Use Could Reduce Risk of AFib in Patients with Type 2 Diabetes

New research from the University of North Carolina suggests the ongoing 

 has slowed progress against cancer deaths in a manner similar to how it has slowed progress against cardiovascular disease.

An analysis of mortality data from 50 million people within the US over a 20-year period, results indicate progress against cancer deaths has continued in the last decade but this progress, specifically among obesity-related cancers, has experienced a slower annual decline in recent years.

"Obesity is a risk factor for many, but not all, types of cancer," said study senior investigator Hazel Nichols, PhD, an associate professor in the Department of Epidemiology at the UNC Gillings School of Global Public Health, 

."We need to make maintaining a healthy weight an obtainable goal for everyone in terms of safe public spaces, availability and affordability of nutritious foods, and other structural factors. The good news in that is if we're able to make these changes as a society, we will be able to improve the health of a nation."

Despite continued advances, many studies indicate improvements in cardiovascular disease mortality in the US began to slow in beginning in 2011 and much of the decline in annual improvements are linked to the growing obesity epidemic. With obesity as a known risk factor for cardiovascular disease and many forms of cancer, investigators designed their analyses as a cross-sectional study of US mortality trends from 1999-2011 and 2011-2018.

Using data from the Centers for Disease Control and Prevention WONDER database, investigators planned to compare trends in cancer and cardiovascular disease-related deaths among all individuals from the database during the aforementioned periods with complete information related to the underlying cause of death, age, sex, race, and ethnicity.

The primary outcome of interest within the study was annual relative rates of change in age-adjusted mortality rates (AAMR) among the overall population and stratified by sex, race, and ethnicity, which was done using Poisson regression. Investigators noted comparisons of AAMR rates of change before and after 2011 were performed using Wald tests.

Using the aforementioned criterion, investigators identified 50,163,483 decedents for inclusion in their analyses. This cohort had a mean age of 72.8 (SD, 18.5) years, 50.1% were female, 79.9% were non-Hispanic White decedents, and 11.7% were non-Hispanic Black decedents.

In 1999, cancer or cardiovascular disease represented 53.6% of total deaths and this figure declined to 44.4% in 2018. When assessing cancer-related mortality, results indicated total cancer mortality improvements experienced greater accelerations from 2011-2018 (annual AAMR relative change, -1.77; 95% CI, -1.67 to -1.86) than 1999-2011 (annual AAMR relative change, -1.48; 95% CI, -1.43 to -1.52) (

Further analysis pointed to a similar trend when assessing decreases in mortality for cancers not associated with obesity in 1999-2011 and 2011-2018. However, when assessing obesity-related cancer mortality, results indicated mortality decline began to slow after 2011, with an annual AAMR relative change of -1.19 (95% CI, -1.13 to -1.26) from 1999-2011 compared to -0.83 (95% CI, -0.70 to -0.96) from 2011-2018 (

Investigators noted the largest decelerations observed in their analyses took place among female decedents (-1.45 [95% CI, -1.36 to -1.53] in 1999-2011 and -0.91 [95% CI, -0.75 to -1.07] in 2011-2018; 

 <.001) and non-Hispanic White individuals (-1.16 [95% CI, -1.09 to -1.22] in 1999-2011 and -0.68 [95% CI, -0.55 to -0.81] in 2011-2018; 

Comparison of 20-Year Obesity-Associated Cancer Mortality Trends with Heart Disease Mortality Trends in the US

A comparison of annual mortality rates related to cancer and cardiovascular disease is shedding light on the impact of the obesity epidemic on progress against both since 1999. 

Rising Obesity Rates Have Had Similar Impact on Progress Against Cardiovascular Disease and Cancer

New research presented at the American Academy of Clinical Endocrinology 30th Annual Meeting (

) suggests levothyroxine sodium (Tirosint-SOL) oral solution can be safely administered as early as 15 minutes before breakfast.

A single-center, open-label, crossover study, results indicate the absorption profile of levothyroxine sodium was clinically equivalent when administered 30 or 15 minutes prior to a high-fat, high-calorie breakfast.

"Levothyroxine is a narrow therapeutic index (NTI) drug that requires no interference from food or beverages for consistent dissolution and absorption", said Murray Ducharme, PharmD, visiting professor at the University of Rhodes, in 

. "The results of this study demonstrate that the wait time needed before breakfast may be shortened to a period of 15 minutes without significant negative effect with the liquid levothyroxine formulation."

With levothyroxine a cornerstone in treatment algorithms for patients with hypothyroidism, Ducharme and a team of colleagues sought to learn more about how the delivery method of levothyroxine sodium might impact the absorption process compared to tablets or soft gel formulations. With this in mind, investigators designed their study as a single-center, phase 1, open-label, randomized, single-dose, 2-period, 2-sequence, crossover trial in 36 healthy volunteers.

The 36 study participants were administered 600 mcg of levothyroxine sodium after a 10-hour overnight fast and 15 or 30 minutes prior to a high-fat, high-caloric meal. For the purpose of analysis, serum concentrations of levothyroxine were measured using a validated LC-MS method serum samples were taken at 3 different times before dosing and at 0.5, 1, 1.5, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours after dosing.

Of note, the meal used in the study consisted of 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with butter, 120 g of hash brown potatoes, and 200 mL of whole milk.

Of the 36 patients included in the study, 36 completed all study periods. The 3 who did not complete the trial failed to do so because of failure to undergo COVID-19 testing, vomiting within 6 hours of dosing, and failure to complete the meal.

Upon analysis, results indicated the median Tmax was unchanged between the treatment arms at 1.5 hours. Investigators pointed out the geometric mean ratios and confidence intervals for the baseline adjusted maximum and extent of exposure were within recognized equivalence boundaries, which indicates an absence of meaningful clinical difference when dosing 15 or 30 minutes prior to a meal.

Investigators also noted there were no differences in adverse events and a total of 11 treatment-emergent adverse events were reported during the trial. Of the 11 events reported, 10 were graded as mild and 1 was graded as moderate. Additionally, 6 were considered possibly related, 1 was considered unlikely related, and 4 were unrelated. No deaths occurred and none of the adverse events that occurred during the trial were considered significant.

A novel solution of Levothyroxine results in clinically similar maximum and extent of exposure whether taken 30 or just 15 minutes before a High-Fat High-Caloric breakfast

Data from a phase 1 trial comparing dosing 15 and 30 minutes prior to breakfast suggests the wait time between intake of the novel liquid formulation of levothyroxine, Tirosint-SOL, and breakfast could be shortened to 15 minutes. 

Phase 1 Trial Indicates Liquid Formulation of Levothyroxine Safe to Administer as Early as 15 Minutes Before Breakfast

While multiple studies have previously outlined the impact of continuous glucose monitors (CGM) on glucose control in patients with diabetes, a new study has returned results suggesting use of CGM did not reduce emergency department visits or hospital readmissions among patients with uncontrolled 

A nonblinded, randomized study presented at the American Academy of Clinical Endocrinology’s 30th Annual Meeting (

), results indicate use of CGM for 2 weeks upon hospital discharge did not result in a significant difference in HbA1c control or rates of hospitalization compared against standard care.

“Contrary to our expectation and hypothesis, continuous glucose monitor use for two weeks immediately post-hospitalization did not lead to reductions in ED visits or hospital readmissions. Our study suggests that further exploration regarding the use of continuous glucose monitors for reduction of hospital readmissions, specifically in type 2 diabetics, is needed,” concluded investigators.

Presented by Carmen Cartwright, MD, an endocrinology fellow at Einstein Medical Center, the current study was conducted by colleagues from the Einstein Healthcare Network’s Department of Endocrinology and sought to explore whether use of CGM immediately after hospitalization could improve glucose control and reduce emergency department visits as well as hospital readmissions. To do so, investigators designed the current study as a prospective, randomized single-center trial randomizing patients to CGM or standard medical management between October 2018 and September 2020.

For inclusion in the trial, patients needed to have type 2 diabetes, be at least 18 years of age or older, and have an HBA1c level equal to or greater than 9%. Additionally, patients were required to have full demographic data and information related to HbA1c levels, sensor and/or glucose logs 2 weeks after discharge, and emergency department visits and hospitalizations up to 6 months following discharge.

In total, 58 patients were enrolled in the study. This group include 28 randomly assigned to the Freestyle Libre Pro CGM for 2 weeks post discharge and the remaining 30 receiving standard medical management. Of note, the mean starting HbA1c was 11.35% in the CGM group and 11.12% in the control group.

Upon analysis, HbA1c improvements in the control and intervention group were not statistically or clinically significant different between the study groups. At 3 months, the mean HbA1c was 8.4% for the control group and 8.3% for the CGM group. At 6 months, these levels were 9.1% and 8.9% for the control and CGM groups, respectively.

When assessing the impact on emergency department visits and hospital readmissions at 6 months, investigators noted a marked, but not statistically significant difference between the study arms. Specifically, 57.1% and 35.7% of the intervention and control groups, respectively, had at least 1 emergency department visits within the 6 months following discharge (95% CI, -0.04 to 46.9; 

=.18). Additionally, 42% and 32.1% of the intervention and control group, respectively, had at least 1 hospital admission within the 6 months following discharge (95% CI, -0.14 to 35.9; 

Subjects whether assigned to continuous glucose monitoring or self-monitoring of blood glucose levels were able to achieve similar hemoglobin A1c reductions.


"We propose this is due to improved education and patient self-awareness for disease monitoring during sentinel hospital visit,” noted investigators.

Reducing ED Visits and Hospital Readmissions and Improving Glucose Control of Patients with Uncontrolled Type 2 Diabetes by Use of Continuous Glucose Monitoring Sensors Placed at Hospital Discharge

Despite the investigators' hypothesis, implementing use of CGM at hospital discharge did not reduce risk of emergency department visits or rehospitalizations among patients with uncontrolled type 2 diabetes. 

Starting CGM Use at Hospital Discharge Did Not Reduce Readmission Risk in Type 2 Diabetes Patients

A new study from Duke University is providing insight into how to improve transitions from pediatric to adult-oriented care for type 1 diabetes mellitus among US patients.

An analysis of electronic health record data from nearly 300 adolescents with type 1 diabetes, results indicate a certified diabetes educator visit, a nutrition visit, or continuous glucose monitor (CGM) use prior to transfer were associated with a shorter gap in care and could reduce risk of adverse events among this patient population.

“The association between certified diabetes educator and CGM use with gap in care should be considered when designing transition programs for adolescents and young adults with type 1 diabetes mellitus,” wrote investigators.

Presented at the American Academy of Clinic Endocrinology’s 30th Annual Meeting (

) by Diana Soliman, MD, an endocrinology fellow of Duke University, the current study was designed by Soliman and colleagues from Duke University Health System to assess associations between clinical characteristics, including sociodemographic factors, comorbidities, health care utilization, and device use, on the timing of transfer from pediatric to adult diabetes care. With this in mind, investigators designed their analysis as a retrospective, longitudinal study of patients from endocrinology clinics within the Duke University Health System.

For inclusion in the study, patients needed to have at least 2 pediatric and 1 adult endocrine visit. Of note, patients who took greater than 3 years to transition to adult endocrinology were excluded from analysis. Investigators planned to use multivariable regression to determine the impact of specific covariates on time to transition from pediatric to adult care.

More than 1500 patients were identified in initial searches. Ultimately, 299 patients were identified for inclusion. Of these 54.85% were female and 73.4% were White. When assessing transition, the mean HbA12c at the last pediatric encounter was 9.4%±2.14% and the median number of months to transition was 14.09 months (4.58-43.80).

After adjustment for sociodemographic factors, gap in care was significantly associated with certified diabetes educator visit, nutrition visits, and CGM use prior to transfer. In comparison, the gap in care was extended among those who were not seen by a diabetes educator (relative effect, 1.80; 955 CI, 1.10-3.05; 

=.02), those who were not seen by a nutritionist (2.30; 95% CI, 1.53-3.46; 

 <.01), and those who were not using CGM prior to transfer (1.67; 95% CI, 1.03-2.71; 

=.04). Additionally, further analysis suggests HbA1c, insulin pump use, ED visits per year, hospitalizations per year, and comorbidities were not significantly associated with the gap in care.

Investigators noted multiple limitations within their study that could limit the applicability of results.

“The study was limited to a single institution and those who transitioned to adult care. The retrospective nature of the study made it difficult to ascertain if patients transitioned to adult care at another clinic,” wrote investigators.

Transition from pediatric to adult care in type 1 diabetes mellitus: A longitudinal analysis of clinical characteristics

A retrospective analysis of EHR data suggests use of CGM or visits from a diabetes educator or nutritionist were associated with a decrease in gaps between receiving care at a pediatric endocrinology clinic and an adult clinic among patients transitioning from pediatric to adult diabetes. 

CGM Use, Visits with Diabetes Educator or Nutritionist Reduce Care Gap Between Pediatric and Adult Diabetes

Data from a pair of phase 3 studies presented at the American Academy of Clinical Endocrinology’s 30th Annual Meeting (AACE 2021) is providing insight into the effect of dose titration schedules with use of osilodrostat (Isturisa) in patients with Cushing’s disease.

Presented by Maria Fleseriu, MD, of Oregon Health and Science University, the analysis of the LINC3 and LINC4 demonstrated the more gradual titration occurring in LINC4 resulted in a lower proportion of hypocortisolism-related adverse events, suggesting up-titration every 3 weeks rather than every 2 weeks could help lower event risk without compromising mean urinary free cortisol (mUFC) control.

“For patients with Cushing’s disease, osilodrostat should be initiated at the recommended starting dose with incremental dose increases, based on individual response/tolerability aimed at normalizing cortisol levels,” concluded investigators.

With approval from the US Food and Drug Administration in March 2020 for patients not eligible for pituitary surgery or have undergone the surgery but still have the disease, osilodrostat became the first FDA-approved therapy address cortisol overproduction by blocking 11β-hydroxylase. Based on results of LINC3, data from the trial, and the subsequent LINC4 trial, provide the greatest available insight into use of the agent in this patient population.

The study presented at AACE 2021 sought to assess whether slow dose up titration might affect rates of hypocortisolism-related adverse events by comparing titration schedules from both phase 3 trials. Median osilodrostat exposure was 75 (IQR, 48-117) weeks and 70 (IQR, 49-87) weeks in LINC3 and LINC4, respectively. The median time to first mUFC equal to or less than ULN was 41 (IQR, 30-42) days in LINC3 and 35 (IQR, 34-52) days in LINC4.

Adverse events potentially related to hypocortisolism were more common among patients in LINC3 (51%, n=70) than LINC4 (27%, n=20). Upon analysis of adverse events, investigators found the most commonly reported type of adverse event was adrenal insufficiency, which included events of glucocorticoid deficiency, adrenocortical insufficiency, steroid withdrawal syndrome, and decreased urinary free cortisol.

Results incited the majority of hypocortisolism-related adverse events occurred during the dos titration periods of each trial. In LINC3, 54 of the 70 (77%) hypocortisolism-related adverse events occurred by week 26. In comparison, 58% of hypocortisolism-related adverse events occurring in LINC4 occurred prior to week 12. Investigators noted most of events that occurred were mild or moderate and managed with dose interruption or reduction of osilodrostat or concomitant medications.

Effect of Dosing and Titration of Osilodrostat on Efficacy and Safety in Patients with Cushing's Disease (CD): Results from Two Phase III Trials (LINC3 and LINC4)

Data from LINC3 and LINC4 provide insight into the impact of dosing titration schedules on risk of hypocortisolism-related adverse events associated with osilodrostat use in patients with Cushing's disease.

More Gradual Dose Titration Could Reduce Hypocortisolism Risk with Osilodrostat in Cushing's Disease

This has been adapted from an article originally published on 

The US Food and Drug Administration's Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) voted 10-7 to support the benefit-risks of teplizumab for delaying clinical type 1 diabetes.

After the vote, experts discussed their reasoning behind their individual vote.

The 10 experts in support of the vote noted that it was a major clinical need and beneficial to at-risk populations. In contrast, the 7 who voted against teplizumab noted the significant result of the study used in the BLA, but had uncertainties about the target population, safety issues, and limited data set.

With a PDUFA date of July 2, the results of the EMDAC vote were highly anticipated as many clincians believe teplizumab could transform the treatment of type 1 diabetes. The BLA was based on TN-10 study data that found a single 14-day course of teplizumab delayed clinical disease and insulin-dependence by at least 2 years in pre-symptomatic patients with Stage 2 T1D, compared to placebo.

According to analysis, more than 800 patients receiving teplizumab in clinical studies and the treatment demonstrated the ability to preserve beta-cell function as shown by C-peptide. Results suggest the treatment was generally well-tolerated and safety data was consistent with previous analyses.

Main risks for the treatment included lymphopenia, transaminase elevations, rash, and cytokine release events, but investigators believe these events are manageable because teplizumab is given as a one-course regimen.

During the meeting, Lauren Wood Heickman, MD, a clinical reviewer at the FDA, provided  an overview on the clinical development for teplizumab. Additionally, Wood Heickman noted that younger age at islet autoantibody development was associated with a higher risk of progression to T1D.

The US Food and Drug Administration's Endocrinologic and Metabolic Drugs Advisory Committee voted 10-7 in support of teplizumab for delaying clinical type 1 diabetes in a meeting on May 27.

Phase 1 Trial Indicates Liquid Formulation of Levothyroxine Safe to Administer as Early as 15 Minutes Before Breakfast

Starting CGM Use at Hospital Discharge Did Not Reduce Readmission Risk in Type 2 Diabetes Patients

CGM Use, Visits with Diabetes Educator or Nutritionist Reduce Care Gap Between Pediatric and Adult Diabetes

More Gradual Dose Titration Could Reduce Hypocortisolism Risk with Osilodrostat in Cushing's Disease

FDA Panels Votes to Support Teplizumab, Potential for Delaying Type 1 Diabetes