
In the DAPA-HF trial, the SGLT-2 inhibitor dapagliflozin improved clinical outcomes in patients wtih heart failure with reduced ejection fraction, with or without type 2 diabetes (T2D). Kieran Docherty, MBChB, discusses results of an important DAPA-HF subanalysis that found dapagliflozin benefits are not affected by background T2D therapy or the type of therapy. Results were presented at the recent 2020 American Diabetes Association Scientific Sessions. 

Videos

VIDEO: Kieran Docherty, MBChB, discusses results of the DAPA-HF analysis on the impact of background T2D therapy on clinical outcomes in patients with T2D and HFrEF. 

Dapagliflozin Effective in T2D with HFrEF Regardless of Type of Background T2D Therapy 

Estimated average A1c for a recent cohort of youth and young adults with type 2 diabetes (T2D) was 8.5%, according to 

 this week at the American Diabetes Association Virtual Scientific Sessions.

Trends in Glycemic Control Among Youth with Diabetes: the SEARCH for Diabetes in Youth Study

, indicate that a substantial percentage of young Americans are not meeting guidline-recommended A1c goals and that glycemic control is worse than it has been for their counterpars from years past. In parrticular, many age groups have worse glycemic control compared to youth and young adults from 2002-2007.

SEARCH for Diabetes in Youth (SEARCH) study

 is the largest and most diverse study of diabetes in youth in the US. SEARCH began in 2000 with funding from the Centers for Disease Control and Prevention (CDC) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and currently has more than 27,000 participants. Participants are from a wide variety of racial and ethnic backgrounds, from 10 different states and visit 1 of 5 US SEARCH study centers (California, Colorado, Ohio, South Carolina and Washington).

“This large, active registry and cohort study of youth diagnosed with diabetes before the age of 20 enables researchers to make assessments of prevalence, annual incidence, and trends by age, race/ethnicity, sex, and diabetes type,” said SEARCH principal investigator and study co-author Dana Dabelea, MD, PhD, director of the Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center and the Conrad M. Riley Endowed Professor at the Colorado School of Public Health. “The SEARCH findings have contributed to a better understanding of the complex and heterogeneous nature of diabetes in youth.”

In the current analysis, researchers examined trends in glycemic control in 6,492 SEARCH participants who had diabetes for more than a year. Participants’ visit data was categorized into three time periods: 2002-2007, 2008-2013, and 2014-2019.

In addition, participants were categorized into 3 groups based on duration of diabetes (1 to 4, 5 to 9, and >10 years) and into 4 groups by age (10 to 14, 15 to 19, 20 to 24, and ≥25 years).

Multivariable regression was used to test differences in A1c over time. Adjustments were made to control for site, age, sex, race/ethnicity, health insurance status, and disease duration.

A substantial percentage of current youth and young adults with diabetes are not meeting current expert recommended A1c goals.

The estimated average A1c for the most recent cohort of youth and young adults with type 1 diabetes was 8.7%, while the most recent group with type 2 diabetes had an estimated average A1c of 8.5%.

Overall, youth and young adults with diabetes who had study visits between 2014 and 2019 had average A1c levels that were comparable to earlier SEARCH cohorts.

However, current youth and young adults with type 1 diabetes in the 10-14, 15-19, and 20-24-year-old age groups continue to have worse glycemic control than the 2002-2007 cohort.

Similarly, participants aged ≥25 years with T2D exhibit a temporal trend of worse glycemic control relative to earlier time periods.

“These results suggest that not all youth and young adults with diabetes are directly benefiting from the increased availability of diabetes technology, newer therapies, and the use of more aggressive glycemic targets for youth with diabetes over time,” said the study’s lead author Faisal Malik, MD, MSHS, assistant professor of pediatrics at the University of Washington School of Medicine, investigator at the Center for Child Heath, Behavior and Development at Seattle Children's Research Institute, and a pediatric endocrinologist at Seattle Children's Hospital.  “Given the evidence highlighting the benefits of tight glycemic control, this study reinforces the need for interventions that combine the use of diabetes technology with effective behavioral and social approaches to improve A1c levels.”

“The increasing trends in the burden and risk of both type 1 and type 2 diabetes suggest there is a need to continue and likely expand comprehensive and sustainable surveillance efforts in youth and young adults,” added Dr. Dabelea.

Articles

ADA 2020. Average A1c for a recent young cohort with type 2 diabetes was 8.5%, according to research presented at the ADA Virtual Scientific Sessions. 

Glycemic Control in US Youth, Young Adults Disappointing 

Physicians’ chronic kidney disease (CKD) awareness in type 2 diabetes (T2D) is associated with CKD severity, according to a

presented this week at the American Diabetes Association’s 80th Virtual Scientific Sessions.

Authors of the retrospective study found that physician awareness of CKD is linked with CKD severity as related to estimated glomerular filtration rate (eGFR), but not to albumin-to-creatinine ratio (ACR).

Researchers examined 136 157 patients aged ≥ 18 years with an electronic health record (EHR) T2D diagnosis that were seen in clinic in 3 consecutive periods; median age was 62 years old. Overall, 77.9% of patients had eGFR measured, 60.6% had ACR measured, and 58.8% had both.

CKD stages were defined by eGFR (represented by G1-G5) and ACR (represented by A1-A3):

The frequency of CKD stages was determined for all patients, regardless of EHR CKD diagnosis.

Researchers found that ACR was measured more often in less severe stages of CKD (Chi-Square, p<.001), and patients in G3a had a CKD diagnosis on their problem list less often vs those in G3b-5 (Chi-Square, p<.001).

Also, among patients in G3a, an EHR CKD diagnosis was present in 53.8%, 58.4%, and 60.1%, while among those in G3b-5 an EHR CKD diagnosis was present in 79.8%, 85.6%, and 84.9% in periods 1-3, respectively.

Among all patients in A2-A3, an EHR CKD diagnosis was present in 44.9%, 44.5%, and 45.7% in periods 1-3, respectively.

“Our data also indicates that despite an initial increase in eGFR-driven CKD awareness between periods 1 and 2, this has leveled off. Not having an EHR CKD Dx suggests lack of physician (and patient) CKD awareness and can potentially lead to suboptimal care,” concluded study authors.

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Schempf J, Freese RL, Caramori L, Harindhanavudhi T. Physicians’ Chronic Kidney Disease (CKD) Awareness over Time in Type 2 Diabetes (T2D). Presented at: American Diabetes Association 80th Scientific Sessions; June 12-16, 2020. Abstract 03-B.

Physicians’ CKD awareness in T2D is linked with CKD severity, suggests a new study presented this week at the American Diabetes Association’s 80th Virtual Scientific Sessions.

Physician CKD Awareness in T2D Patients Linked to CKD Severity

In patients with heart failure with reduced ejection fraction (HFrEF), the sodium glucose cotransporter-2 dapagliflozin reduced the incidence of new onset type 2 diabetes (T2D) by 32% vs placebo.

 at the 2020 American Diabetes Association Virtual Scientific Sessions by lead investigator Silvio Inzucchi, MD, professor of Medicine, Yale School of Medicine, clinical chief, section of endocrinology, and medical director of the Yale Diabetes Center.

In the video above, Patient Care spoke with Dr Inzucchi about the results of this study, “Effect of dapagliflozin on the incidence of diabetes: a prespecified exploratory analysis from DAPA-HF” and the original  DAPA-HF trial and asked for his thoughts on the role of SGLT-2 inhibitors in T2D treatment in primary care.

VIDEO: Silvio Inzucchi, MD, discusses results of a prespecified analysis of the DAPA-HF trial, which found that dapagliflozin reduced new onset diabetes by 32% in patients with heart failure. 

DAPA-HF: Dapagliflozin Reduces Incident T2D in Adults with Heart Failure 

Hurried communication and inadequate explanation of health status and care can negatively impact glycemic control in black patients with type 2 diabetes (T2D), according to research presented this week at the American Diabetes Association’s 80th Virtual Scientific Sessions.

The disparities in outcomes among black patients with T2D compared with those among white patients are not fully explained by patient and system-level factors, according to study authors.

, researchers examined domains of the patient-provider relationship and their associations with race and glycemic outcomes in patients with T2D. A total of 115 black and 106 white patients with T2D representing 34 primary care practices completed the study (mean age, 64.4 years; 55% women; average A1c, 7.3% [blacks, 7.4%; white, 7.3%]).

The Interpersonal Process of Care (IPC) survey was used to measure 7 domains that describe the patient-provider relationship:

Adjusted linear regression models revealed no significant main effects of any of the subscales in the overall cohort.

However, race interactions for 2 of the subscales achieved statistical significance.

Among black patients who reported no hurried communication, A1c was on average 0.45% lower [95% CI, -1 to 0.1] vs black patients who reported some hurried communication (p=0.48). Among black patients who reported that providers fully explained results and medications, A1c was on average 0.64% lower [95% CI, -1.19 to -0.08] than among those who did not endorse a full explanation of results and medications from providers (p=0.01).

No such relationship was observed between these IPC subdomains and improved glycemic control among white patients.

Racial disparities in glycemic control, the authors note, could be improved using interventions that target communication in the patient-provider relationship particularly with respect to time spent in discussion and in explaining results and medications.
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Source: Reid H, Lin O, Fabbro RL, et al. Provider communication in black patients with T2DM is associated with glycemic control. Presented at: American Diabetes Association 80th Scientific Sessions; June 12-16, 2020. Abstract 52-LB.

ADA 2020: Glycemic control was worse for black patients who experienced hurried interaction with healthcare providers than for those who did not, a new study reports. 

Rushed HCP Interactions with Black Patients Erode Glycemic Control

A comprehensive telehealth program delivered to rural patients with poorly controlled type 2 diabetes (T2D) resulted in a reduction in A1c levels at 6 months, according to research presented at the American Diabetes Association’s 80th Virtual Scientific Sessions

The improvement—a 1.36% reduction in A1c—was maintained up to 18 months after the program initiation.

Diabetes management in rural areas is problematic because of limited access to specialists as well as to self-management programs. Under an award form the Veterans Administration (VA) Office of Rural Health--Iowa City, researchers designed an intensive diabetes management program called the 

Advanced Comprehensive Diabetes Care (ACDC)

The program was specifically designed for delivery using the existing Veterans Health Administration’s Home Telehealth (VHA HT) infrastructure and clinical staff.

The 6-month telehealth intervention combines telemonitoring with module-based self-management support and medication management.

Existing clinical staff with VHA HT delivered ACDC through bi-monthly half-hour calls. In an 

, researchers found that ACDC improved A1c, blood pressure, and diabetes self-care in the initial 50 veterans who participated. Since 2017, ACDC has been implemented in clinical practice at 7 VHA sites around the country that serve rural veterans.

The most recent analysis examined 125 patients receiving ACDC at 5 sites. Across all locations, patients’ average A1c levels improved from 9.25% at baseline to 7.89% at 6 months, a benefit that largely persisted 18 months after the start of the study. On qualitative analyses, ACDC enhanced patient engagement and awareness of diabetes control.

“We are pleased to see that the intervention was well-suited for delivery in clinical practice and that it remained effective in real-world settings,” said Elizabeth Kobe, a study investigator and MD candidate at Duke University Medical School.

“When telehealth interventions are designed to leverage existing resources, they can greatly improve diabetes care in underserved rural populations. We also believe this design-minded approach can extend to other chronic diseases.”

ADA 2020. Improvement in glycemic control among US veterans was seen across 5 study sites and was sustained at 18 months after study initiation, says study reported at the ADA 80th Virtual Scientific Sessions. 

Intensive Telehealth Program Improves A1c In Rural Patients with Type 2 Diabetes 

A novel once-weekly basal insulin analog demonstrated comparable efficacy and safety vs once-daily insulin glargine U100 (IGlar U100) in insulin-naïve type 2 diabetes (T2D) poorly controlled on oral antidiabetes drugs (OADs), according to 

 on Sunday, June 14, 2020, at the 80th Annual American Diabetes Association Virtual Scientific Sessions

In the 26-week, randomized, double-blind, double-dummy, treat-to-target, phase 2 trial, participants (n = 247) were randomized 1:1 to the investigational insulin icodec (icodec; n = 125) or to IGlar U100 (n = 122). At baseline, patients were inadequately controlled (A1c 7.0-9.5%) with metformin with or without a dipeptidyl peptidase-4 (DPP-4) inhibitor.

Starting doses were icodec 70 U weekly and IGlar U100 10 U daily, with weekly titration to a pre-breakfast self-monitored blood glucose (SMBG) target of 70-108 mg/dL. 

Baseline characteristics appeared similar in both groups; mean age was 59.6 years, diabetes duration 9.7 years, BMI 31.3 kg/m2 and fasting plasma glucose (FPG) 181 mg/dL. Mean baseline A1C was 8.1% for the icodec group and 8.0% for the IGlar U100 group.

The primary endpoint was change in A1c from baseline to week 26 and secondary endpoints included change in FPG from baseline to week 26 and hypoglycemic episodes.

At week 26, estimated mean A1c was 6.69% for icodec and 6.87% for IGlar U100 (estimated mean change from baseline: -1.33% and -1.15%-points, respectively).

There was no statistically significant treatment difference for change in A1c from baseline to week 26 (-0.18%, 95% CI, -0.38; 0.02).

Estimated mean FPG at week 26 was 123 mg/dL (icodec) and 127 mg/dL (IGlar U100).

Observed rates of level 2 (<54 mg/dL) + 3 (severe) hypoglycemia were low (60.55 and 52.36 events per 100 patient years of exposure for icodec and IGlar U100, respectively) and were comparable (

There were no unexpected safety findings.

Insulin icodec is the first once-weekly insulin with similar glucose-lowering effects and safety profile to once-daily IGlar U100. Study authors note that icodec could improve treatment acceptance and facilitate T2D management in patients needing basal insulin.

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Dapagliflozin Reduces Incident T2D in Patients with HFrEF

Next Generation "Artificial Pancreas" Improves Glycemic Control, A1c in T1D

SGLT-2 Inhitibor Delays Insulin Initiation, Intensification in T2D with CVD

ADA 2020. An investigational once-weekly insulin proved comparable in safety and efficacy to traditional once-daily insulin glargine in findings presented at the ADA 80th Annual Virtual Scientific Sessions.  

Novel Once-weekly Basal Insulin Found Comparable to QD Insulin Glargine

— The SGLT2 inhibitor dapagliflozin prevented incident type 2 diabetes (T2D) in patients with heart failure (HF), according to results of the study titled “Effect o

f dapagliflozin on the incidence of diabetes: A prespecified exploratory analysis from DAPA-HF,"

 presented today at the American Diabetes Association’s80th Virtual Scientific Sessions.

 was a phase 3 placebo-controlled international study of dapagliflozin (Farxiga, AstraZeneca) in people with chronic heart failure and a reduced ejection fraction (HFrEF). The trial enrolled people both with and without T2D. The 4,774 study participants, average age 66 years, were randomly assigned to take either 10 mg of dapagliflozin or a placebo once daily and were followed for 18.2 months. 


The study found the risk of worsening HF or death from cardiovascular causes was lower among patients treated with dapagliflozin than those who received the placebo, regardless of the presence or absence of T2D.

The current planned analysis assessed whether dapagliflozin reduced the incidence of T2D in the 2,605 trial participants who did not have T2D when the study began.

Of the participants without T2D, 1,298 had been assigned to the dapagliflozin group, and 1,307 to the placebo group. New-onset T2D was defined as A1c ≥ 6.5% on two consecutive study visits throughout the median 18.2-month follow-up.

A total of 157 participants developed T2D, 150 of whom had prediabetes (A1c 5.7-6.4%) at the beginning of the study.


The people who developed T2D had higher average A1c levels, greater body mass index and lower eGFR at the beginning of the study than those who did not develop diabetes. 


Cox proportional hazards model data showed dapagliflozin reduced new-onset diabetes by 32%, with 4.9% of dapagliflozin patients (64 of 1,298) developing T2D, compared to 7.1% (93 of 1,307) in the placebo group.

In an additional exploratory analysis, those patients who did develop diabetes during the trial experienced a 70% increase in mortality, after adjustments for baseline features.


“Our sub-study within the DAPA-HF trial demonstrates that diabetes prevention could be considered an additional benefit of dapagliflozin, whose main effect, of course is to reduce cardiovascular mortality and worsening heart failure in patients with heart failure and reduced ejection fraction,” said Silvio Inzucchi, MD, lead investigator and professor of medicine at the Yale University School of Medicine.

“The 32% relative risk reduction compares favorably with the 31% reduction with metformin, as reported in the Diabetes Prevention Program. We will need to do more studies to see if this effect extends to patients without heart failure and reduced ejection fraction and to evaluate how durable the benefit might be and how long diabetes prevention persists after the discontinuation of therapy.”

ADA 2020. Dapagliflozin reduced new onset type 2 diabetes in patients with heart failure with reduced ejection fraction, according to a study released today at the ADA 80th Virtual Scientific Sessions. 

Empagliflozin significantly and durably reduces the need for insulin initiation and the need for large dose increases in current insulin users with type 2 diabetes (T2D), according to 

 Friday, June 12, 2020 at the American Diabetes Association’s® Virtual 80th Scientific Sessions.

Delay to initiation of insulin was longer among those recently diagnosed.

Insulin use in treatment of T2D is associated with weight gain and hypoglycemia, requires training and education, can be costly, and increases daily disease management burden, state Muthiah Vaduganathan, MD, MPH, and colleagues in the study abstract. They note that "reducing insulin need is attractive to both patients and practitioners."

, 7020 patients with type 2 diabetes at high cardiovascular risk were treated with the sodium-glucose co-transporter-2 inhibitor empagliflozin 10, 25 mg, or placebo against a background of standard care. Median follow-up was 3.1 years.

After the first 12 weeks, changes in background glucose-lowering therapy were permitted.

Researchers assessed treatment effects of pooled empagliflozin vs placebo on time to new initiation of insulin among insulin-naïve patients and time to total daily insulin dose increase by >20% among insulin-treated patients.

In 3633 (52%) insulin-naïve patients, empagliflozin reduced the need for insulin use vs placebo by 54% (11.1% vs. 22.3%; HR 0.46 [0.39-0.54]), adjusted for key covariates (baseline A1c, time since T2D diagnosis, BMI, eGFR, geographic region and treatment status) .

In 3387 (48%) patients using insulin at baseline, empagliflozin reduced need for a >20% increase in insulin dose by 57% (19.1% vs. 36.8%; HR 0.43 [0.37-0.49]).

Reduction in incident insulin use was most pronounced in patients within 5 years of T2D diagnosis (HR 0.31 [0.21-0.45]) vs T2D duration of >5-10 yrs (0.42 [0.31-0.59]) or >10 yrs (0.56 [0.44-0.71); P interaction=0.03. 

In patients with T2D and CVD, empagliflozin markedly and durably delays the need for insulin initiation, more so in those recently diagnosed, and reduces need for large dose increases in those already using insulin.

EMPA-REG OUTCOME was an FDA-mandated trial to assess the cardiovascular safety of all new diabetes drugs. Results of the trial, first reported in November 2015, indicated that empagliflozin was superior to placebo in improving glycemic control and reducing CV events in patients with T2D and established CVD.

ADA2020: Empagliflozin significantly, durably delays need for insulin and for large dose increases, in patients with type 2 diabetes and cardiovascular disease, finds study presented at ADA 80th Scientific Sessions. 

ADA2020: SGLT-2 Inhibitor Delays Insulin Initiation, Intensification in T2D with CVD

CHICAGO (June 12, 2020)—A “next generation” automatic insulin delivery system (AID) improved daytime blood sugar control and improved A1c levels among adolescents and young adults with type 1 diabetes (T1D) without an increase hypoglycemia, according to research presented today at the American Diabetes Association’s® (ADA’s) 80th Scientific Sessions.

The results of this first comparison of a next generation AID system to a currently approved one were shared during the presentation, “FLAIR—An NIDDK-sponsored international, multi-site randomized crossover trial of AHCL vs 670G.”

Despite the use of multiple daily injections or insulin pumps and continuous glucose monitoring (CGM), many individuals with T1D require additional glycemic control—but without increasing the daily burden of living with diabetes.

Youth with T1D in particular often have difficulty achieving optimal glycemic control, which is essential to help reduce the risk for diabetes complications

AID systems—sometimes referred to as artificial pancreas—are rapidly becoming a standard of care in the management of T1D. The 

 (Fuzzy Logic Automated Insulin Regulation) study compared the efficacy and safety of 2 systems manufactured by Medtronic—the new Advanced Hybrid Closed-Loop (AHCL) and the 670GHybrid Closed-Loop (HCL). The latter is one of 2 FDA-approved AID systems

FLAIR enrolled 113 patients with T1D at 7 international diabetes centers. The participants, aged 14 to 29 years, used each AID system for 3 months in a randomized crossover trial.

Standardized pump training, including how to account for meals and exercise, was provided to all participants and their diabetes care partners.

Focusing on the biggest challenge for AID systems--how effective they are at preventing high blood glucose levels during the day--the researchers compared the 2 systems and evaluated how participants adjusted to the daily use of the technology.

•  Percentage of time in range (TIR) over 24 hours (ie, blood sugar levels from 70-180 mg/dL) was superior with AHCL vs HCL. TIR went from 57% at baseline to 67% (AHCL) and 63% (HCL).

•  The number of individuals achieving the international TIR consensus target of > 70% TIR increased nearly 3-fold from baseline when using AHCL vs increasing almost 2-fold with HCL.

•  Baseline average A1c levels were 7.9% and A1c decreased to 7.4% with AHCL vs 7.6% with HCL.

•  Both systems were safe when evaluating events of level 3 hypoglycemia or diabetic ketoacidosis.

•  Responses to a user satisfaction survey showed patients preferred the AHCL over the HCL system.

“This age group has traditionally been the most difficult group in which to optimize glucose management and the FLAIR study shows that individuals using any type of therapy, even insulin injections without a pump or CGM system, can benefit from the next generation AHCL AID therapy,” said Richard Bergenstal, MD, co-primary investigator of FLAIR, executive director of the International Diabetes Center at HealthPartners, and past ADA President of Medicine & Science, in an ADA press release.

“There is much interest in the future of advanced technology to treat type 1 diabetes," he added, "and the AHCL system is a significant step forward for adolescents or young adults who have a hard time managing their glucose levels.”

ADA 2020: A new automatic insulin delivery system improves glycemic control in young people with type 1 diabetes, according to research presented at the American Diabetes Association Virtual Scientific Sessions. 

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