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

ADA 2021

Patrick Campbell is the senior editor of Endocrinology Network, as well as its sister publication Practical Cardiology. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. In his free time, he enjoys traveling, sports, and exploring the great outdoors. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

A new study presented at the American Diabetes Association’s 81st Scientific Sessions (ADA 2021) details the projected impact of Medicare Part D Senior Savings Model (SMM) on diabetes-related health expenses and economic outcomes among patients using insulin covered by Medicare.

With rising costs of medications a focus at 

 the University of Florida College of Pharmacy-led study suggests the Medicare Part D SSM would provide relief to more than 1.2 million insulin users and also indicates use of the savings model could reduce the risk of complications in this patient population.

With an overall interest in the cost-effectiveness of diabetes treatments, Hui Shao, MD, PhD, an Assistant Professor at the University of Florida College of Pharmacy, designed multiple studies presented at ADA 2021 designed to explore how the cost of diabetes management has changed in recent years, including a study assessing the 

cost-effectiveness of newer glucose-lowering agents

 to older agents. The current study was designed to evaluate the impact of the Medicare Part D SSM on clinical and economic outcomes among Medicare insulin users.

To do so, the investigators designed their study to use data from the 2015-2016 iteration of the National Health and Nutrition Examination Survey (NHANES) and inputting this information into the Building, Relating, Validating, Assessing Outcomes (BRAVO) Diabetes microsimulation model with the specific aim of simulating the impact of the savings model on diabetes complications, quality0adjusted years of life (WALY), and medical costs.

Results of the investigators’ analysis suggested 1.29 million insulin users covered by Medicare were projected to be eligible for Medicare Part D SSM in 2021. Results of the model suggest the SSM insulin policy was associated with relative risk reductions of 5.61% for stroke, 3.27% for angina, 3.79% for MACE, and 3.49% for cardiovascular mortality at 5 years.

Over 5 years, the simulation model suggested SSM was projected to increase $2.0 billion in medical costs, which correlates to $1573 per person, with a gain of 7750 QALYs added (ICER: $157,300 per QALY). Over 20 years, the simulation model suggested the Medicare Part D SSM was associated with an additional $.5 billion in medical costs with an increased QALYs by 72,095 (ICER: $57,900 per QALY). Based on these calculations, investigators suggest the policy would need to be in place for longer than a 5-year period to reduce costs among this patient population.

For more on this study and the potential impact of the Medicare Part D SSM on Medicare patients using insulin, 

reached out to Shao and that conversation is the subject of this ADA 2021 House Call.

Projected Impact of the Medicare Part D Senior Savings Model (SSM) on Diabetes-Related Health and Economic Outcomes among Insulin Users Covered by Medicare

Articles

A simulation model assesses the projected impact of the Medicare Part D Senior Savings Model on healthcare spending and outcomes among patients covered by Medicare using insulin. 

Estimating the Impact of the Medicare Part D Senior Savings Model on Expenses for Insulin Users on Medicare

A study examining the impact of real-time continuous glucose monitoring (CGM) has returned results suggesting use of real-time CGM was associated with decreased diabetes-related expenses among patients with type 2 diabetes.

While many studies have detailed the impact of real-time CGM on outcomes or time-in-range among patients with type 2 diabetes, the current study, which was presented at the 

American Diabetes Association’s 81st Scientific Sessions (ADA 2021)

, demonstrates use of real-time CGM was associated with a mean reduction in spending per-person-per-month of $424.

“This study provides real-world evidence that real-time CGM use was associated with reductions in diabetes-related medical costs for people with type 2 diabetes. Increased access to real-time CGM may help reduce diabetes-related costs of care,” said Gregory Norman, PhD, an Adjunct Professor at the University pf California, San Diego and the Director of Health Economics and Outcomes Research with Dexcom, during his presentation at ADA 2021.

As the popularity of real-time CGM continues to increase, the research emphasis on these devices has begun to shift from outcomes to impact on medical costs and quality of life among patients using the technology. With this in mind, Norman and a team of colleagues designed the current study as a retrospective analysis of administrative claims data from within the Optum Research Database with the aim of assessing how implementation of real-time CGM might influence diabetes-related medical costs.

For the purpose of analysis, investigators sought to identify patients who initiated real-time CGM between October 2017-February 2019. Index date was defined as the earliest observed use of real-time CGM. To be eligible for inclusion, patients needed to be commercial or Medicare Advantage beneficiaries, have no evidence of pregnancy or type 1 diabetes in the year prior to index date, and have 1 or more claims with real-time CGM during the identification.

Investigators noted patients were required to be continuously insured for at least 1 year prior to index date and needed at least 6 months of follow-up data after beginning real-time CGM. The primary outcomes of interest were the total diabetes-related costs during the baseline and follow-up periods as well as the change in per-person-per-month costs, which was assessed using paired t-tests.

In total, 571 patients were identified for inclusion. This cohort had a mean age of 51.2 (SD, 11.9) years, 46% were female, 99% had commercial insurance, 80% were treated with intensive insulin therapy, 58% were seeing an endocrinologist, and 92% reported having comorbidity complications. In the year prior to initiating real-time CGM therapy, the mean per-person-per-month cost associated with diabetes management was $1680 (SD, $4519) compared to $1256 (SD, $3679) after starting real-time CGM. This equated to a reduction of $424 per-person-per-month in diabetes-related costs after initiating real-time CGM (95% CI, -816 to -31; 

Further analysis suggested the majority of this reduction was driven by reductions in diabetes-related inpatient medical costs (-$358; 95% CI, -706 to -10; 

 <.044) Investigators also pointed out the mean number of inpatient hospital stays and days spent hospitalized were reduced by -0.42 days per-person-per-month.

Real-Time Continuous Glucose Monitor (RTCGM) Use Associated with Decreased Diabetes Medical Costs for Patients with Type 2 Diabetes (T2D),”

A look at the medical spending of more than 500 patients with type 2 diabetes who initiated therapy with real-time continuous glucose monitoring details the reductions in medical costs associated with initiation of real-time CGM. 

Real-Time CGM Use Associated with Reduced Medical Costs in Patients with Type 2 Diabetes

Once a distant idea discussed at scientific sessions as an approach years away from implementation, use of telehealth and remote patient monitoring have become a necessity as a result of the COVID-19 pandemic.

Further proving this point is an analysis from the American Diabetes Association’s 81st Scientific Sessions 

 outlining the use of telehealth services for monitoring glycemic control among patients with type 2 diabetes from nearly a dozen healthcare systems across the US.

"The emergence of digital health tools like connected devices and mobile apps for self-management has not only helped people with type 2 diabetes in the daily management of their disease but also facilitated the sharing of their data with their care teams," said Mark Clements, MD, PhD, a practicing endocrinologist and Chief Medical Officer of Glooko, which sponsored the current study, 

. “These results demonstrate that, with access to patient data, care teams can identify patients with sub-optimal glycemic control and provide them with timely, remote-based interventions outside of routine clinic visits that lead to significant glycemic improvements in the near term as well as on a sustainable basis."

Presented at ADA 2021 by Sarine Babikian, PhD, the current study was designed to assess whether enrolling in a remote patient monitoring pilot program might help improve glycemic control in patients with type 2 diabetes. Using telehealth platforms, all program participants were instructed to sync blood glucose meters with a mobile app or using computer-based software and were followed for up to 12 months. As part of the program, patients had access to coaching and other remote-based interventions.

In total, investigators identified 424 participants to take part in their pilot study. This population was 46% female and had a median age of 50 (IQR, 42-59) years. Among these, 331 reached the 3-month follow-up, 228 reached the 6-month follow-up, and 129 completed 12 months of follow-up.

Upon analysis, overall trends of immediate and sustained improvements were observed for mean blood glucose levels (baseline: 178 mg/dL to approx. 155 mg/dL at 3, 6, 12 months; 

< .05) and mean proportion of in-range (baseline: 60% to approx. 74% at 3, 6, 12 months; 

<.05) and high SMBG measurements, which was defined as greater than 250 mg/dL (baseline: 14% to approx. 8% at 3, 6, 12 months; 

< .05). Investigators also pointed out there were no difference in the proportion of patients with hypoglycemia.

“We found that glycemic improvements were observed within 3 months of RPM program enrollment and then they were sustained with continued participation. These kinds of programs that incorporate remote data sharing and coaching can support and maintain positive glycemic control for people living with type 2 diabetes,” said Babikian during her presentation.

Immediate and Sustained Trends in Glycemic Control during Remote Patient Monitoring in People with Type 2 Diabetes

A study assessing use of remote patient monitoring in patients with type 2 diabetes outlines the impact continued participation in digital monitoring programs can have on glycemic control among this patient population.

ADA 2021 Study Outlines Benefits of RPM on Glycemic Control in Patients with Type 2 Diabetes

An analysis of the FIDELIO-DKD trial is providing clinicians with insight into the effects of finerenone based on use of background GLP-1 receptor agonist (GLP-1RA) therapy.

With the popularity of GLP-1RA use having grown since FIDELIO-DKD began in 2015, data from the prespecified analysis demonstrate use of finerenone resulted in consistent kidney and cardiovascular benefits when compared against placebo, irrespective of GLP-1RA use among patients in the phase 3 trial.

“There was consistent kidney and cardiovascular benefit of finerenone compared to placebo, irrespective of GLP-1 receptor agonist use,” said Peter Rossing, MD, DMSc, Head of Complications Research and Chief Physician at Steno Diabetes Center, who presented the analysis at the 

. “There was a reduction in albuminuria with finerenone in both groups, which could suggest that finerenone can reduce albuminuria further on top of GLP-1 receptor agonist use.”

One of a trio of prespecified analyses of FIDELIO-DKD assessing the effects of finerenone according to background therapy, results of the current study provide some of the first insight into the effects of Bayer’s novel, non-steroidal, selective mineralocorticoid receptor agonist based on background therapy use. The other studies presented at ADA 2021 examined use according to SGLT2 inhibitor use and background insulin therapies.

Briefly, FIDELIO-DKD was a randomized, double-blind, placebo-controlled trial enrolling 5674 patients with type 2 diabetes, a UACR from 30-5000 mg/g, an eGFR from 25-74 mL/min/1.73min2, and receiving optimized RAAS blockade that was 

originally presented at the American Society of Nephrology’s Kidney Week 2020

. Results of the trial indicated finerenone use was associated with an 18% reduction in risk for progression of CKD and a 14% reduction in the composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.

Of the 5674 patients included in FIDELIO-DKD, 394 (6.9%) were receiving a GLP-1RA at baseline. Investigators noted 368 (6.5%) patients began therapy with a GLP-1RA during the course of the trial. Compared to their counterparts not treated with GLP-1RAs, those using GLP-1RAs had a higher BMI, higher HbA1c, greater diuretic use, greater statin use, lower median UACR, and a lower prevalence of cardiovascular disease.

Check out a similar FIDELIO-DKD analysis assessing impact of finerenone according to baseline SGLT2 inhibitor use

Upon analysis, results indicated no between-group differences exist for interaction between the kidney and cardiovascular outcomes in the trial. Additionally, results suggested reductions in UACR seen in the trial were independent of GLP-1RA use, with LS-means of 0.63 (95% CI, 0.56-0.70) in the GLP-1RA group and 0.69 (95% CI, 0.67-0.72) in the group not using GLP-1RAs (

 for interaction=.20). Investigators also pointed out safety analysis indicated incidence of hyperkalemia events was similar among both groups of patients.

For more on the results of this secondary analysis of FIDELIO-DKD, 

reached out to Rossing and that conversation is the subject of this ADA 2021 House Call.

Efficacy and Safety of Finerenone in Patients with CKD and T2D by GLP-1RA Treatment,

A FIDELIO-DKD analysis presented at ADA 2021 suggests the renal and cardiovascular benefits of finerenone were consistent, irrespective of background GLP-1 RA use and indicate the presence of both was associated with even greater reductions in albuminuria. 

Finerenone Provides Consistent Benefit, Irrespective of Background GLP-1 RA Use

A study from investigators at the UCLA David Geffen School of Medicine and Harvard Medical School is calling for greater attention to patients with type 1 diabetes progressing from adolescence to young adulthood.

Results of the study, which assessed nearly 20,000 person-years of data, indicate HbA1c monitoring declines substantially as adolescent patients transition to adulthood, which could lead to a greater risk of adverse events later in life.

“Adolescents and young adults with type 1 diabetes are at-risk of not receiving the recommended levels of annual HbA1c testing, but extent to which this occurs and the degree to which this may due to not accessing care or changes in physicians is poorly understood,” wrote investigators.

Presented at the American Diabetes Association’s 81st Scientific Sessions 

 by Lauren Risk, PhD, an Assistant Professor in the Division of General Internal Medicine and Health Services Research at UCLA, the current study sought to assess how provider type might impact HbA1c monitoring. Specifically, investigators hoped to assess whether frequency at which this population does not receive twice-yearly HbA1c tests and the degree to which such rates are associated with age, not accessing care at all, and the types of physicians delivering diabetes care.

To do so, investigators identified a cohort of 9,916 patients with type 1 diabetes aged 13-26 years old who were continuously insured by a large health insurer for 12 months or from during 2012-2016. Among this group, 61.2% reported seeing an endocrinologist, 40.1% reported seeing a pediatrician, and 31.8% reported undergoing HbA1c tests less than twice yearly. Additionally, this patient population provided investigators with 18,927 person-years of follow-up data.

Upon analysis, investigators found the percentage of those not receiving twice-yearly HbA1c tests rose from 17% at the age of 13 years to 40% at the age of 26 years, with this percentage peaking at 45% at 24 years. Additionally, the percent not making any diabetes visits within a calendar year rose from 12% to 17% from the ages of 13 to 26 years old.

At the age of 13 years, pediatric endocrinologists and general pediatricians were the dominant providers, representing 62% and 26%, respectively, of all providers. At the age of 26 years, adult endocrinologists (48%) followed by adult primary care physicians (44%) were the most dominant providers. Results of the investigators’ analyses suggested the most common age at transfers from pediatric to adult physicians appeared to be 18 years for primary care and 19 years for endocrinologists.

In adjusted analysis, results indicated patients receiving care provided by an endocrinologist were more likely to undergo twice-yearly HbA1c testing.

“Observed declines in HbA1c monitoring appear to be related to both not accessing healthcare despite being insured and to transferring the types of providers utilized,” wrote investigators. “Given demographic correlates of accessing subspecialty care and HbA1c monitoring, improving continuity of subspecialty care may mitigate disparities in care quality.”

HbA1c Monitoring among Adolescents and Young Adults with Type 1 Diabetes: Impact of Diabetes Care Provider Type

A study assessing factors associated with achieving recommended levels of HbA1c testing provide insight into the impact of provider type and other factors on the likelihood of having at least 2 HbA1c measurements in a year. 

Strategies Needed to Improve Transition from Pediatric to Adult Diabetes Care in Type 1 Diabetes

A new literature review presented at the 

 detail how the rising cost of glucose-lowering medications have been crushing the agents’ ability to be cost-effective.

Using data from a dozen cost-effectiveness studies of glucose-lowering agents published from 2000-2018, results of the study indicate the prices of DPP-4 inhibitors and SGLT2 inhibitors have nearly doubled since their market entrance and also suggest about 50% of the studies published in 2018 found use of newer medication was not a cost-effective option for patients.

With the rising cost of diabetes management becoming an issue for many, Hui Shao, MD, PhD, Assistant Professor at the University of Florida College of Pharmacy, and a team of colleagues sought to explore how the cost of newer glucose-lowering has influenced their cost-effectiveness compared to older therapies. To do so, investigators designed their study as a systematic literature review to identify US-based cost effectiveness studies comparing DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors with older glucose-lowering drugs.

Searching for studies conducted between 2000-2018, a total of 12 studies were identified for inclusion. For inclusion in the literature review, studies needed to collect data related to treatment duration, costs, effectiveness, discount rates, and the incremental cost-effectiveness ratio (ICER) of newer and older drugs. For the purpose of analysis, measurements of the total payment for medication claims were extracted from the 2018 IBM MarketScan Commercial Claims database.

Upon analysis, investigators found only 1 of the 12 studies suggested older drugs were cost-effective based on drug costs prior to 2010. However, after updates based on the 2018 pricing of these agents, results suggested 58% (n=7) of studies were in favor of the older glucose-lowering drugs.

All 4 studies comparing newer agents to thiazolidinediones favored newer glucose-lowering drugs in the initial analysis, but all 4 studies favored thiazolidinediones after the cost update. In 4 studies comparing newer agents against sulfonylureas, 2 suggested sulfonylureas were more cost-effective after the 2018 cost update. Additionally, all 4 studies suggested newer drugs were cost-effective compared to insulin in the original study and just 1 drew a different conclusion when using the updated drug costs. Investigators highlighted a sensitivity analysis indicated these results were robust up to a 30% cost rebate.

Investigators pointed out the drug prices of metformin, sulfonylurea, and thiazolidinedione in 2018 had decreased to 46%, 22%, and 8%, respectively, of their market prices in 2005. In contrast, the cost of DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors increased to 1.9, 1.8, and 1.4 times the cost of the price of market entrance, respectively. 

To learn more about the changing cost-effectiveness of newer glucose-lowering agents, 

and that conversation is the subject of this ADA 2021 House Call.

The Diminishing Cost-Effectiveness of the Newer Glucose-Lowering Drugs in the United States, 2010-2018

While advances in glucose-lowering therapies have been practice-changing, a new analysis suggests patients could achieve greater cost-effectiveness with older agents. 

Diminishing Cost-Effectiveness Hurting Case for New Glucose-Lowering Agents

 found use of dapagliflozin (Farxiga) reduced the onset of diabetes by 32% in patients with heart failure, new research from DAPA-CKD suggests use was associated with a 38% reduction in new onset diabetes among those with chronic kidney disease (CKD) from the phase 3 trial.

While investigators noted failure to reach statistical significance, they purport results still provide evidence linking use of dapagliflozin to a decrease in the incidence of the type 2 diabetes among patients seen in either phase 3 trial.

“In this nondiabetic population with chronic kidney disease of different types, we looked into the progression to diabetes during the duration of the trial and we saw approximately a 30% reduction in progression. It was of the exact same magnitude of the reduction of progression to diabetes as was seen in the DAPA-HF study,” said Peter Rossing, MD, DMSc, Head of Complications Research and Chief Physician at the Steno Diabetes Center, in an interview with 

With a DAPA-HF analysis presented at the previous year’s conference, the 

 analysis was designed with the intent of assessing how use of dapagliflozin might influence rate of new-onset diabetes in patients with CKD. A prespecified exploratory analysis, the current study assessed a subgroup of 1398 patients with no prior history of diabetes and an HbA1c less than 6.5% at baseline.

During a follow-up period lasting a median of 2.4 years, 4.7% (33 of 701) of the placebo group and 3.0% (21 of 697) of the dapagliflozin group, which investigators pointed out responded to event rates of 2.4 per 100-patient years in the placebo group and 1.5 per 100-patient years in the dapagliflozin group. Results of the investigators’ analyses indicated dapagliflozin was associated with a 38% reduction in risk of developing type 2 diabetes (HR, 0.62; 95% CI, 0.36-1.08).

No heterogeneity was observed in regard to the effect of dapagliflozin on diabetes prevention based on most subgroups, including those based on age, glycemic status, blood pressure, eGFR, and other factors. However, investigators noted the effect was more pronounced in female patients (

for interaction=.03). Of those who went on to develop diabetes during the trial, 90% had prediabetes at baseline.

In a meta-analysis coming data from DAPA-CKD and DAPA-HF, results suggested dapagliflozin was associated with a 34% reduction in new-onset diabetes (HR, 0.66; 95% CI, 0.51-0.87; 

=.003), without heterogeneity between studies (

“In these groups of people where you have a high risk for cardiovascular disease, kidney disease, and metabolic complications, you can prevent diabetes or at least delay diabetes,” added Rossing.

For more on the results of this study and the implications for dapagliflozin use as clinicians and researchers push for greater uptake in primary care settings, check out our ADA 2021 House Call with Rossing.

Dapagliflozin and the Incidence of Type 2 Diabetes in Patients with Chronic Kidney Disease

A prespecified analysis of DAPA-CKD presented at ADA 2021 suggests use of dapagliflozin reduced the incidence of type 2 diabetes by nearly 40% among patients with chronic kidney disease but without diabetes within the phase 3 trial.

Dapagliflozin Cuts Risk of Diabetes in Patients with Chronic Kidney Disease

New research presented at the American Diabetes Association 81st Scientific Sessions (ADA 2021) suggests those with poor diabetes management were at a greater risk of severe COVID-19 outcomes.

A retrospective look at data from more than 350 patients admitted to a single medical center in Texas, results indicate there was no difference in outcomes based on diabetes status alone, but those with unmanaged diabetes had more severe COVID-19 and a slower rate of recovery than their counterparts with more effective diabetes management.

“Our results highlight the importance of assessing, monitoring, and controlling blood glucose in hospitalized COVID-19 patients from the start, specifically for vulnerable populations already at risk of comorbidities,” said lead investigator Sudip Bajpeyi, PhD, Director of Metabolic Nutrition and Exercise Research at University of Texas at El Paso, in a statement.

With an interest in describing the differences in outcomes and disease course among patients with diabetes, Bajpeyi and a team of colleagues from the University of Texas at El Paso designed their study as a retrospective analysis of data from patients admitted to the University Medical Center in El Paso, TX. Overall, 369 patients were identified for analysis. This group had a mean age of 60.15±0.8 years and a mean BMI of 30.28±0.4 kg/m2, and 243 had diabetes.

Patients were categorized according to HbA1c level at time of hospitalization. These groups were defined as normoglycemic (HbA1c less than 5.7%), prediabetes (5.7% to less than 6.5%), and diabetes mellitus (6.5% or greater). For the purpose of analysis, investigators assessed the severity of COVID-19 outcomes through quick sepsis-related organ failure assessment (qSOFA) and length of hospitalization was measured as number of days spent inside the hospital. Investigators also noted plans for further assessment within the diabetes mellitus group according to medication use.

Upon analysis, results indicated there were no significant differences observed among groups for severity of COVID-19 infection, with a qSOFA scores of 0.24±0.08, 0.38±0.07, and 0.28±0.03, respectively, for the normoglycemic, prediabetes, and diabetes mellitus groups (

 >.05). Additionally, no significant differences were observed when elating potential differences in length of hospitalization with mean lengths of stay of 5.6±0.8, 9.3±1.0, and 8.9±0.6 days, respectively, among the normoglycemic, prediabetes, and diabetes mellitus groups (

However, results indicated patients with diabetes not using medication appeared to have significantly greater severity (qSOFA: 0.44±0.08 vs 0.22±0.03; 

<.05) and length of hospitalization (10.8±1.6 vs 8.2±0.6 days; 

<.05) compared to patients managing their diabetes with medication.

Unmanaged Diabetes as a Poor Prognostic Factor in the Severity of Infection and Recovery Time of Hospitalized COVID-19 Patients

While investigators found no differences in outcomes based on diabetes status alone, results indicated those who were not managing their diabetes had more severe outcomes and longer length of hospitalization from COVID-19. 

Unmanaged Diabetes Linked to More Severe COVID-19, Longer Stays in Hospital

Adding finerenone to treatment algorithms already containing an SGLT2 inhibitor could result in even greater renoprotective benefits, according to a new FIDELIO-DKD analysis.

American Diabetes Association 81st Scientific Sessions (ADA 2021)

, the secondary analysis assessed the effect of finerenone according to background SGLT2 inhibitor use and found consistent benefit across all subgroups. Results also suggested patients using SGLT2 inhibitors had a greater UACR improvement than those not using SGLT2 inhibitors at baseline.

“What we see actually is that the effect seems to be additive, which seems to be in line with the concept that they work through different mechanisms. Where the SGLT2 inhibitors protect the kidney by hemodynamic actions and finerenone protects the kidney by preventing fibrosis and inflammation,” said Peter Rossing, MD, DMSc, Head of Complications Research and Chief Physician at Steno Diabetes Center in Copenhagen, in an interview with Endocrinology Network, who cautioned against overinterpretation of results due to a small sample size.

With the recent revelations of SGLT2 inhibitors’ cardiorenal protective benefits an increased emphasis has been placed on the use of agents in the class. Add to this the growing excitement surrounding finerenone and the present analysis was among the most anticipated late-breaking abstracts from ADA 2021.

A randomized, double-blind, placebo-controlled trial enrolling 5674 patients with type 2 diabetes, a UACR from 30-5000 mg/g, an eGFR from 25-74 mL/min/1.73min2, and receiving optimized RAAS blockade, results of FIDELIO-DKD indicated use of finerenone was associated with a significantly reduced rate of the primary and secondary outcomes. Results of the study suggested 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.

Of the 5673 included in FIDELIO-DKD, 259 (4.6%) were receiving an SGLT2 inhibitor at baseline. Investigators noted SGLT2 inhibitor use was initiated among 328 patients after the study began. Analysis based on use of SGLT2 inhibitors indicated results were consistent irrespective of use at baseline for the primary (

Additionally, results suggested patients receiving finerenone had reductions in UACR without use of SGLT2 inhibitors (ratio of LS-means, 0.68; 95% CI, 0.65-0.71; 

 <.0001) but investigators also pointed out UACR reductions appeared to be greater among those using SGLT2 inhibitors at baseline (ratio of LS-means, 0.75; 95% CI, 0.62-0.90; 

=.0024). Further analysis indicated treatment-emergent hyperkalemia events occurred less often in those using SGLT2 inhibitors compared to those not using an SGLT2 inhibitor.

Finerenone in Patients with CKD and T2D by SGLT2i Treatment: An Analysis of the FIDELIO-DKD Study

Data from an analysis of FIDELIO-DKD suggests the renoprotective benefits of finerenone were consistent irrespective of SGLT2 inhibitor use and those using an SGLT2 inhibitor with finerenone resulted in greater UACR reductions.

Finerenone and SGLT2 Inhibitors Could Have Additive Effect on Kidney Protection

While practice-changing discoveries and regulatory decisions happen once in a decade for most specialties, endocrinologists and diabetes specialists have had front row seats to multiple in recent years.

The revelation of SGLT2 inhibitors’ cardiorenal protective effects has taken main stage at the American Diabetes Association (ADA)’s recent conferences, but a majority of the discussion ahead of ADA 2021 is related to another familiar glucose-lowering agent: semaglutide. With the lower dose semaglutide a staple in treatment of type 2 diabetes, many diabetes specialists and endocrinologists, alike, were excited by the news of the US Food and Drug Administration’s 

decision to approve semaglutide 2.4 mg (Wegovy)

 for chronic weight management, which was the first approval for such an indication from the FDA since 2014.

Now, excitement around the GLP-1RA continues to grow as 

 plans to evaluate the oral version of the semaglutide to determine if it could provide similar benefits on body weight in a phase 3a study.

With an interest in learning more about the approval, what it means for clinicians and patients, and what the future of obesity management looks like, 

 reached out to Thomas Wadden, PhD, Former Director of the Center for Weight and Eating Disorders at Penn Medicine and principal investigator of STEP 1 and STEP 3, and that conversation is the subject of this special edition Endocrine Outlook podcast.

Ahead of ADA 2021, Dr. Thomas Wadden discusses the significance of the semaglutide 2.4 mg (Wegovy) approval for chronic weight management and Novo Nordisk's plans to evaluate an oral version. 

ADA 2021 Deep Dive into Semaglutide 2.4 mg: A Turning Point for Obesity Management?

Adam Sturts, DO, is an internal medicine resident at Penn State Hershey Medical Center with an interest in cardiovascular health and endocrinology. Sturts is a graduate of the Rowan University School of Osteopathic Medicine and a type 1 diabetic.

Early on October 31, 1920, the Canadian orthopedic surgeon Sir Frederick Banting, MD, awoke suddenly with an idea that transformed type 1 diabetes mellitus from a certain death sentence to a treatable chronic medical condition. He penned the idea in his journal: “Diabetus. Ligate pancreatic ducts of dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate the internal secretion of these to relieve glycosurea.”

Thanks to the efforts of Banting and his research team, John Macleod, Charles Best and James Collip among others, insulin was first isolated in 1921.

Prior to the discovery of insulin, there was no effective treatment for type 1 diabetes. Patients were prescribed starvation diets in a futile attempt to prolong their short, agonizing lives. Most died months after diagnosis.

Leonard Thompson, a 14-year-old type 1 diabetic, was the first to directly benefit from the discovery of insulin. He was severely malnourished, dehydrated and critically ill with diabetic ketoacidosis when he presented to Toronto General Hospital. After starting insulin injections in 1922, his condition improved and he lived for an additional 10 years. Dr. Banting and Macleod won the Nobel Prize in Physiology or Medicine in 1923 for their discovery and this is still the fastest time from discovery to Nobel Prize award. Millions of diabetic lives have been saved by insulin in the 100 years since discovery, including my own.

I vividly remember the day I was diagnosed with diabetes on August 5th, 1998, my 5th birthday, and the first insulin injection that I received. My initial insulin regimen included pork insulin and NPH. The injections and finger sticks for blood glucose monitoring were painful, but I tolerated them because I knew that without them I would be unwell. My family supported me through these early years. My friends affectionately nicknamed me “Juice Box.” Support systems through JDRF and Camp Nejeda, a camp for diabetic children, were essential to my family’s and my own psychological wellbeing. Eventually, I transitioned to insulin lispro and glargine then insulin aspart and glargine.

In 2006, I got my first insulin pump the Medtronic MiniMed Paradigm 511. The pump was truly a paradigm shift in the management of my diabetes because it allowed me to live more freely. I continued insulin pump therapy throughout undergraduate, physical therapy school and added a Dexcom G4 Platinum CGM in medical school with improvements in glycemic control and glycemic understanding. Preparation for medical residency not only included studying medicine and clinical rotations but also anticipating the impact of long hours, high stress and constantly changing schedule on my glycemic control.

I transitioned to the t:slim X2 insulin pump with Control-IQ hybrid closed loop technology coupled with Dexcom G6 CGM based on the efficacy and safety of this system demonstrated in the 

Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes

. The hybrid closed loop system has features, including automatic insulin adjustments, correction boluses and activity settings, that have been absolute game changers for me. I can sleep more comfortably knowing that the Control-IQ algorithm will decrease my basal rate and alert me if I am trending towards hypoglycemia. When rounding in the hospital I can glance at my pump and instantly see my blood glucose, alleviating the stress of not knowing and allowing me to focus on the care of my patients rather than worrying about my own blood glucose.

I am grateful for all of the therapeutic and technological advances since the discovery of insulin. We have come so far since 1921 but we still have many challenges to overcome moving forward.

Banting ultimately sold his patent for insulin for $1 because “Insulin does not belong to me; it belongs to the world.”

Unfortunately, the cost of insulin has increased substantially in recent years—the average price of insulin has nearly tripled since 2002, 

. Patients’ out of pocket costs are typically based on list price so our expenses have risen substantially. The factors responsible for this price increase are unclear. I am fortunate that I have had the financial means of affording insulin and diabetes supplies. Other diabetics are not so fortunate and pay the price with their lives.

Fortunately, the American Diabetes Association, the Endocrine Society, JDRF, and others continue to advocate for patients with diabetes to create reform to reduce costs and improve the affordability and accessibility of insulin and diabetes supplies. Resources such as insulinhelp.org and getinsulin.org can help patients find affordable insulin and I encourage physicians to share this information with diabetic patients.

My experience at the ADA 81st scientific sessions leave me optimistic that near term therapeutic advances involving “smart” insulins, advanced insulin delivery systems, closed-loop systems, and artificial pancreases will improve the lives of diabetic patients. My hope is that by 2121 we will be celebrating the anniversary of the cure for type 1 diabetes.

This piece represents the views and opinions of the author and do not reflect the views of the publication, MJH Life Sciences, or any other organizations.

Using the ADA's celebration of the 100-year anniversary of the discovery of insulin as a backdrop, resident Advisory Board member Adam Sturts, DO, reflects on the history, present, and future of insulin from the perspective of a provider and a patient with type 1 diabetes. 

100 Years of Insulin: Perspective from a Provider with Type 1 Diabetes

Outcomes data from the phase 3b SUSTAIN FORTE trial suggest the investigational 2.0 mg version of semaglutide provided greater reductions in HbA1c and body weight than semaglutide 1.0 mg (Ozempic).

With multiple studies related to primary outcomes and subgroups findings form the phase 3b trial, research presented at the 

 demonstrated the ability of semaglutide 2.0 mg once-weekly could provide greater reductions in HbA1c and body weight than the 1.0 mg version with a comparable safety profile.

”Some people living with type 2 diabetes require additional support to reach their blood glucose targets,” said Juan Frias, MD, Medical Director of the National Research Institute and principal investigator of SUSTAIN FORTE, in 

. “The reductions in blood glucose seen with semaglutide 2.0 mg demonstrate that a higher dose of Ozempic® may offer individuals the opportunity to further improve their diabetes control, with comparable tolerability to Ozempic® 1.0 mg."

With Novo Nordisk announcing the submission of a label extension application to the US Food and Drug Administration for the 2.0 mg dose in May 2021, data related to SUSTAIN FORTE, which was used as the basis of the application, were among the most anticipated at this year’s ADA conference. The data included a pair of studies, one detailing the overall efficacy and safety outcomes of the trial and the other detailing the effects of semaglutide 2.0 mg versus semaglutide 1.0 mg according to baseline bodyweight and HbA1c level.

A 40-week trial comparing once-weekly semaglutide 2.0 mg versus semaglutide 1.0 mg as add-on to metformin with or without sulfonylureas, SUSTAIN FORTE enrolled 961 patients with type 2 diabetes with an HbA1c of 8.0-10.0%. All patients in the trial initiated treatment with a 0.25 mg dose of semaglutide that was doubled every 4 weeks until the target dose was achieved.

The primary endpoint of the study was to provide evidence demonstrating the superiority of semaglutide 2.0 mg vs 1.0 mg on glycemic control. Investigators also sought to compare the effects of the investigational 2.0 mg dose effects on body weight, safety, and tolerability compared to the 1.0 mg dose.

Overall results of the trial indicted semaglutide 2.0 mg was associated with statistically significant and superior reductions in HbA1c (2.2% vs 1.9% [ETD, -0.23; 95% CI, -0.36 to -0.11; 

 <.001]) and body weight (-6.9 kg vs -6.0 kg [ETD, -0.93; 95% CI, -1.68 to -0.18; 

=.016]) than the 1.0 mg dose. Additionally, the semaglutide 2.0 mg arm of the trial saw a greater proportion of patients achieve an HbA1c less than 7% (67.6% vs 57.5% [OR, 1.60; 95% CI, 1.21-2.13; 

=.001]) or a body weight reduction greater than 5% (59.2% vs 51.3% [OR, 1.41; 95% CI, 1.08-1.84]) than the semaglutide 1.0 mg arm.

In the subgroup analysis, investigators assessed change in HbA1c and body weight based among those with an HbA1c of less than 9.0% versus 9.0% and above and those with a BMI less than 35 kg/m2 versus 35 kg/m2 and above. In these analyses, results demonstrated semaglutide 2.0 mg was associated with greater reductions in HbA1c and body weight compared to semaglutide 1.0 mg, irrespective of baseline HbA1c or BMI.

“Ozempic® has helped millions of people with type 2 diabetes worldwide lower their blood sugar, reduce their risk of major cardiovascular events in adults with established cardiovascular disease and has demonstrated weight reduction for some patients,” said Martin Lange, executive vice president of Novo Nordisk. “For almost a century, our mission has been to drive change in diabetes treatment and innovation to improve the lives of people living with diabetes. These data show us that with a higher 2.0 mg dose of semaglutide, we can help even more adults living with type 2 diabetes, who are not at glycemic control, lower their HbA1c.”

Efficacy and Safety of Once-Weekly Semaglutide 2.0 vs. 1.0 mg for Type 2 Diabetes: SUSTAIN FORTE Randomized Trial,

Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg vs. 1.0 mg by Baseline HbA1c and BMI: SUSTAIN FORTE Subgroup Analyses

A pair of studies presented at ADA 2021 detail the effects of an investigational 2.0 mg dose of semaglutide compared to semaglutide 1.0 mg (Ozempic) on glycemic control and body weight in patients with type 2 diabetes in SUSTAIN FORTE.

Semaglutide 2.0 mg Proves Superiority vs Ozempic for Glycemic Control, Weight Loss in SUSTAIN FORTE

Results of a randomized clinical trial presented at the American Diabetes Association’s 81st Scientific Sessions 

 demonstrate spinal cord stimulation provided durable pain relief and quality of life improvements over the course of a year.

In what investigators are calling the largest randomized clinical trial assessing spinal cord stimulation for management of painful diabetic neuropathy, results of SENZA-PDN indicate use of high-frequency (10 kHz) spinal cord stimulation was associated with reductions in reported pain and improvement in quality of life compared to conventional medical management alone at 12 months.

“10 kHz spinal cord stimulation shows a durable impact on pain maintained to 12 months. We will continue our follow-up up to 24 months with further evaluation of health economic data and other indicators,” said Erika Petersen, MD, Director of the Section of Functional and Restorative Neurosurgery at University of Arkansas Medical School, during her presentation at ADA 2021.

With diabetic neuropathy a difficult to treat condition among patients with diabetes, a research emphasis has been placed on identifying avenues of attenuating the impact diabetic neuropathy can have on the quality of life of patients with diabetes. With this in mind, SENZA-PDN was designed with the intent of assessing whether 10 kHz spinal cord stimulation could provide durable, long-term relief of pain without comprising neurological health of patients.

SENZA-PDN was funded by Nevro Corporation and enrolled 216 patients who underwent 1:1 randomization to either high-frequency spinal cord stimulation plus standard medical management or standard medical management alone. For inclusion in the study, patients needed to have painful diabetic neuropathy symptoms for 12 months or more, lower limb pain measured as 5 cm or more on the VAS, and an HbA1c of 10% or more. Outcomes of interest included changes in pain, neurological function, and quality of life.

Ultimately, 113 patients were randomized to spinal cord stimulation and 103 were randomized to medical management alone. With 6-month data published in 

, the ADA 2021 study detailed outcomes from the trial’s 12-month analyses. Of note, patients randomized to conventional medication management could opt to crossover to the alternative treatment after 6 months.

At 6 months, 82% of patients randomized to conventional medical management opted to cross over to the treatment arm of the trial. Investigators pointed out no patients in the spinal cord stimulation group opted to switch to conventional medical management.

At 12 months, results demonstrated clear, sustained benefits of 10kHz were observed in regard to lower limb pain, pain interference with daily living, sleep quality and activity. Additionally, patients receiving spinal cord stimulation appears to have improvements of neurological function during examinations. In safety analyses, investigators noted 5 instances of explantation due to infection occurred during the trial.

“Interestingly, we identified that neurological improvements were observed in many patients with 10 kHz stimulation although the mechanism of action is not understood,” added Petersen, during her presentation.

Long-Term 10 kHz Spinal Cord Stimulation in Painful Diabetic Neuropathy: A Randomized Controlled Trial

Data from a RCT demonstrate the impact of high-frequency spinal cord stimulation on pain and quality of life among patients with a history of painful diabetic neuropathy lasting more than a year.

SENZA-PDN: High-Frequency Spinal Cord Stimulation Provides Durable Pain Relief Out to 12 Months

Data obtained from the T1D Exchange registry presented at the American Diabetes Association’s 81st Scientific Sessions 

 suggest engagement in such a program could lead to improvements in diabetes management and care.

A look at data from more than 1000 patients with type 1 diabetes who completed the Exchange’s annual questionnaire, results of the study detail a group of highly engaged patients who met their HbA1c targets, but also reported experiencing severe hypoglycemic and symptoms of diabetes-related ketoacidosis.

"This data show that these highly engaged Registry participants are doing well meeting their A1c levels with support from advanced technology, which is fantastic, but there is still room for therapeutic improvement and uptake of diabetes technology," said Wendy Wolf, PhD, Vice President of Registry and Outcomes Research at T1D Exchange, 

 "There are few large U.S. datasets like our Registry that are capturing the authentic experience of people living with T1D. By understanding how people self-manage their disease, the community receives a more complete picture than relying on clinical data alone."

Created in June 2019, the T1D Exchange Registry was designed with the goal of providing clinicians with longitudinal data on disease, health status, and self-reported outcomes among patients with type 1 diabetes. A mobile-friends online platform that allows patients to enroll in less than 20 minutes, the registry contained more than 7600 patients with type 1 diabetes as of March 2021.

The ADA 2021 analysis was created to assess the current state of disease management, technology utilization, and rate of disease complications among patients who had completed the baseline entry questionnaire and the 1-year annual questionnaire. Of the 7630 patients enrolled in the registry, 1063 had completed the annual questionnaire at the time of analysis.

These patients had a mean age of 45.2 years, with patients ranging in age from 4 years to 85.7 years. The mean duration of diabetes among these patients was 25.8 years. At enrollment, the mean HbA1c was 7.2% and, at the 1-year follow-up, this figure had decreased to 6.8%.

Further analysis indicated the cohort within the T1D Exchange registry had begun a rapid uptake in use of CGM during the first year of enrollment, with 88.8% reporting use of CGM at follow-up compared to 82.5% at enrollment. Additionally, 78.6% reported use of an insulin pump in the 1-year questionnaire compared to 74.7% at the time of enrollment. Investigators also pointed out 58.2% reported carrying a glucagon kit and 11.2% reported use of medications other than insulin to lower blood sugar.

Overall, 15% of patients included in the analysis reported experiencing severe hypoglycemia within the past 12 months and 6.7% reported diabetes-related ketoacidosis symptoms during the 12 months since enrollment.

Research from the T1D Exchange Registry paints a picture describing current trends in the management of diabetes among patients with type 1 diabetes enrolled within the online registry. 

100 Years of Insulin: Perspective from a Provider with Type 1 Diabetes

Semaglutide 2.0 mg Proves Superiority vs Ozempic for Glycemic Control, Weight Loss in SUSTAIN FORTE

SENZA-PDN: High-Frequency Spinal Cord Stimulation Provides Durable Pain Relief Out to 12 Months

T1D Exchange Registry Data Provides Insight into Current Trends of Management in Type 1 Diabetes

Background Insulin Use Does Not Impact Benefits of Finerenone in Diabetic Kidney Disease