A provider toolkit with clinically relevant resources related to diagnosis and management of central precocious puberty.

CPP Provider Toolkit

A pair of experts in the management of diabetes review the role of insulin therapy and review the approval process for biosimilars, including the FDA's approval of the first interchangeable insulin biosimilar.

Interchangeable Insulin Biosimilars: A Game Changer in Diabetes Management

Podcast hosted by Diana Isaacs, PharmD, and Natalie Bellini, DNP aimed at providing real-world perspective on the latest advances in diabetes management.

The US Food and Drug Administration has issued an alert to users related to a potential cybersecurity risk for Medtronic MiniMed 600 Series Insulin Pump Systems.

Announced on September 20, the FDA’s alert, which pertains to multiple systems including the MiniMed 630 G and MiniMed 670G, points out the agency had not been made aware of any reports related to this cybersecurity vulnerability. The FDA’s alert also noted 

Medtronic has issued an Urgent Medical Device Correction

 on their own website notifying users as well as providing recommended actions.

“There is a potential issue associated with the communication protocol for the pump system that could allow unauthorized access to the pump system. If unauthorized access occurs, the pump’s communication protocol could be compromised, which may cause the pump to deliver too much or too little insulin,” noted the 

FDA’s September 20 Cybersecurity alert.

On their website, Medtronic provides the Urgent Medical Device Correction, a list of model numbers impacted by the issue, and a multitude of frequently asked questions for device users. Within these resources, Medtronic notes the issue was identified through an internal review and, while the event meets the definition of a recall, users are not required to return their devices.

, which was signed by Chirag Tilara, vice president of Quality at Medtronic Diabetes, and Robert Vigersky, MD, chief medical officer at Medtronic Diabetes, the pair recommended all patients turn off the “Remote Bolus” feature on their pump if it is turned on, which is on by default. The letter also urged users to conduct any connection linking of devices in a nonpublic setting. Additional recommended precautions from Medtronic included keeping pump and connected system components within user control at all times, be attentive to pump notifications, alarms, and alerts, and immediately cancel any boluses you or your care partner did not initiate.

“Medtronic has recently identified a potential issue through internal testing whereby, under specific circumstances, the communication between the components of the pump system could be compromised through unauthorized access,” reads the letter. “For unauthorized access to occur, a nearby person other than you or your care partner would need to gain access to your pump at the same time that the pump is being paired with other system components. This cannot be done over the internet.”

In the aforementioned release, the FDA noted they are working with Medtronic to identify, communicate, and prevent adverse events related to this incident. The FDA urged those with questions to reach out to Medtronic at 1-800-646-4633, option 1.

Articles

Announced on September 20, the alerts from the FDA and Medtronic notify users of a potential cybersecurity risk identified through internal testing at Medtronic that would allow unauthorized users to the pump's communication protocol, which could allow unauthorized boluses.

Cybersecurity Risk with MiniMed 600 Systems Prompts Alert from FDA, Medtronic

Data from a study led by investigators from the University of Texas and the University of Miami is providing insight into the effects of bariatric surgery on long-term body weight and risk of comorbidities in adolescent populations with 

An analysis of data from nearly 100 patients who underwent metabolic and bariatric surgery at 21 years of age or younger, results of the study suggest undergoing such a procedure was associated with a mean reduction in body weight of 31.3% more than a decade after undergoing surgery, with results indicating undergoing surgery was also associated with long-term 

“There are long-term benefits to completing bariatric surgery before the age of 22,” said Sarah Messiah, PhD, MPH, senior author of the study and professor and director of the Center for Pediatric Population Health at UTHealth School of Public Health-Dallas, 

. “The durability of the positive health outcomes isn’t well known this far out at this young age. It’s been a gap in understanding that this research has helped fill.”

As the obesity epidemic has ballooned, so has the popularity and knowledge base surrounding bariatric surgery as a potential treatment for obesity. In more recent years, bariatric surgery among adolescent populations has begun to increase as the safety of procedures has become more well-established. However, as investigators of the current study note, fewer research efforts have been undertaken to examine the long-term impact of metabolic and bariatric surgeries beyond 10 years of follow-up in adolescent populations.

With this in mind, Messiah and colleagues designed the current study as an analysis of long-term outcomes after bariatric surgery in patients aged 15-21 years before surgery and with a minimum of 10-18 years of follow-up from a single academic medical center. In total, 96 individuals who underwent surgery between 2002-2010 were identified for inclusion in the investigators’ analyses. Before surgery, this cohort had a mean age of 18.7±1.6 years, a median BMI of 45.0 kg/m2, and 83% were female. Investigators also pointed out 5.2% had type 2 diabetes, 13.5% had hypertension, and 14.6% had hyperlipidemia.

The majority of patients (90.6%) underwent gastric bypass while 9.4% underwent laparoscopic adjustable gastric banding )LAGB, and 1.0% underwent sleeve gastrectomy. The mean follow-up time of participants was 14.2±2.2 years. Upon analysis, results indicated the mean total decrease in body weight among adolescents who had undergone bariatric surgery was 31.3% (IQR, 20.0-38.9%), with body weight reductions of 32.0% (IQR, 21.3-40.1%) observed among RYGB participants and 22.5% (IQR, 0.64-28.3%) among LAGB participants.

Further analysis suggested individuals with hyperlipidemia, and diabetes or hyperglycemia before surgery reported 100% remission at follow-up (

 <.05). Investigators also pointed out decreases in the prevalence of multiple comorbidities was decreased at baseline compared to before surgery, including hypertension (13.5% vs 1%; 

 <.001), gastroesophageal reflux disease (13.5% vs 3.1%; 

“Adolescents are the fastest-growing segment of the severe obesity epidemic in the US, and the COVID-19 pandemic has exacerbated the problem,” Messiah added. “The evidence from this study supports recent recommendations from the American Academy of Pediatrics to increase access to surgery for adolescents. We hope this data could change barriers to access for these children.”

Long-Term Outcomes after Adolescent Bariatric Surgery

Journal of the American College of Surgeons.

An analysis of nearly 15 years of follow-up data from 97 patients who underwent bariatric surgery during adolescence provides insight into the benefits of surgery on weight loss and comorbidities among those with severe obesity. 

Benefits of Bariatric Surgery in Adolescents Endure Beyond a Decade, Study Shows

After demonstrating efficacy and safety as a weight loss agent in randomized clinical trials, a retrospective cohort study from a Mayo Clinic-led team is providing insight into the real-world effects of 2.4 mg semaglutide (Wegovy) for weight management.

With data from more than 150 patients treated at a referral center for 

 prescribed semaglutide for 3 months or more between January 1, 2021-March 15, 2022, results of the study suggest the mean weight loss achieved at 3 months was 5.9% of body weight, with this improving to 10.9% at 6 months and further analysis indicating more than 50% of semaglutide users achieving weight loss of 10% or more at 6 months.

“This study may be a stepping stone to demonstrating the effectiveness of semaglutide for patients aiming to lose weight. These results may support the applicability of semaglutide in a less controlled environment, as previously proven in RCTs,” wrote investigators.

US FDA’s approval of 2.4 mg semaglutide

 in June 2021 for chronic weight management in patients with overweight or obesity, the weekly GLP-1 receptor agonist became the first drug to receive such an approval in more than half a decade. Based on the results of the pivotal STEP program, the agent boasted a mean weight loss of 6% of body weight at 3 months and 12% of body weight at 28 weeks. Now, more than a year removed from FDA approval, investigators launched the current study citing a lack of retrospective studies assessing effectiveness of the increased doses of semaglutide outside of a clinical trial setting.

Designed as a retrospective review of electronic medical record data from individuals in the Mayo Clinic Health system using 1.7 mg or 2.4 mg semaglutide from January 1, 2021-March 15, 2022, the study’s primary endpoint of interest was the percentage of weight loss, with secondary endpoints examining the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months as well as the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months. For inclusion in the investigators’ analyses, individuals were required to have a BMI of 27 kg/m2 or greater and be prescribed weekly semaglutide for 3 months or more. Major exclusion criteria included hoister of bariatric procedures, receipt of other antiobesity medications, and have an active malignant neoplasm.

A total of 408 patients were identified for potential inclusion. After application of exclusion criteria and those who were denied based on insurance or a national shortage of semaglutide, 175 individuals were identified for inclusion in the investigators’ final analyses. This cohort had a mean age of 49.3 (SD, 12.5) years, 75.4% were female, and 88.0% were White. The cohort had a mean BMI of 41.3 (SD, 9.1) kg/m2, 16.0% had type 2 diabetes, and 58.3% had 6-month follow-up data available.

Upon analysis, results indicated the mean weight loss at 3 months was 6.7 (SD, 4.4) kg, which was equivalent to a mean weight loss of 5.9% (SD, 3.7%) (

 <.001). At 6 months, the mean weight loss was 12.3 (SD, 6.6) kg, which was equivalent to a mean weight loss of 10.9% (SD, 5.8%) (

 <.001). Among the 102 patients with at least 6 months of follow-up, 87.3% achieved a weight loss of 5% or more, 54.9% achieved a weight loss of 10% or more, 23.5% achieved a weight loss of 15% or more, and 7.8% achieved a weight loss of 20% or more. Further analysis suggested people with type 2 diabetes had. A lower mean percentage of weight loss at 3 months (3.9% [SD, 3.1%] vs 6.3% [SD, 3.7%]) and at 6 months (7.2% [SD, 6.3%] vs 11.8% [SD, 5.3%]) compared to their counterparts without type 2 diabetes (

“The findings of this cohort study suggest that semaglutide is clinically effective for weight loss at 3 and 6 months for people with overweight or obesity,” investigators added. “Although our study lacked the stringent and closely controlled nature of RCTs, we report similar weight loss results within the same time period as in RCTs. Studies with greater sample sizes and longer periods of follow-up are further needed to support the effectiveness of semaglutide.”

Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity

A retrospective analysis of EMR data from Mayo Clinic referral centers provides an overview of the effects of 2.4 mg semaglutide on weight loss in populations outside of clinical trial settings. 

Real-World Data Backs 2.4 mg Semaglutide (Wegovy) for Weight Management in Obesity

The COVID-19 pandemic, now in its third year, has led to a host of setbacks in public health in addition to its specific toll on human lives. As a result of widespread lockdowns, many people have been stuck inside with little to do. With greater than 40% of American adults already struggling with obesity, the pandemic was thought to increase social isolation while decreasing access to health care and high-quality nutritious food sources.

A recent investigation by Jaime Amandoz, MD, and colleagues in Texas found nearly one-third of people with 

 gained more than 5% of their body weight in the first year of the COVID-19 pandemic, with 1 in 7 gaining 10%. Amandoz believes the increased anxiety produced in obese patients due to their increased risk for serious COVID-19 illness and death is the driving force behind the dramatic weight gain.

“The COVID-19 pandemic is a fascinating model for individual and social stress and showed that changes in mental health can really preclude people from maintaining a healthy body weight,” Amandoz said.

Leveraging surveys, the investigators of this study found very high levels of self-reported stress, anxiety, depression, and maladaptive eating behaviors among adults with obesity during the COVID-19 pandemic.

 Prior research by this team of investigators looked at the impact of stay-at-home orders on the mental health and behaviors of obese patients. They found that 70% of patients found weight loss to be more difficult during the lockdowns with large portions reporting less exercise and more stress-related eating.

In the current report, Amandoz and fellow researchers found that the majority of obese patients surveyed gained around 4.3% of their body weight during the pandemic.

 Another study cited in their work showed that 48% of all American adults gained weight during the pandemic further supporting these new data.

 Those surveyed tended to be of higher education and economic status. The investigators speculate that those of lower socioeconomic status likely faced even greater stress and more weight gain.

Factors associated with greater weight gain included eating less healthy food, not sleeping as much, and exercising less.

Finally, those people reporting the highest levels of anxiety, depression, and stress gained the most weight.

“It’s not just about telling people to eat less and move more, there’s a mental health aspect that has to be integrated into treating the whole person as well,” Amandoz notes.

These results make sense. The stress of a pandemic coupled with isolation and fear put a significant strain on the mental health of obese patients already struggling to lose weight. As we move into and beyond the third year of COVID-19 we as clinicians need to evaluate our patients for stress, anxiety, and depression making available to them enhanced support and targeted interventions. When access to care is limited, we need to find alternatives such as virtual visits and responsible office encounters. Education and encouragement become even more important when our patients are dealing with mental health challenges. Addressing those mental health challenges should be a part of every visit.

Every effort needs to be made to identify those patients at highest risk for weight gain. The challenges experienced by isolated obese patients should not be underestimated. The stigma and mental health problems already experienced by obese patients should be assumed to be significantly worse during the pandemic but with support, understanding, and encouragement, we can mitigate the added strain. Amandoz points out that people in weight management programs typically lose weight.

As such, we should do everything we can to get obese patients in and keep them in these programs, programs that should evaluate and address the patients mental as well as physical health.

Almandoz JP, Xie L, Schellinger JN, et al. Changes in body weight, health behaviors, and mental health in adults with obesity during the COVID-19 pandemic. Obesity (Silver Spring). 2022;1‐12. doi:10.1002/oby.23501

Khubchandani J, Price JH, Sharma S, Wiblishauser MJ, Webb FJ. COVID-19 pandemic and weight gain in American adults: a nationwide population-based study. Diabetes Metab Syndr. 2022;16: 102392. doi:10.1016/j.dsx.2022.102392

New research from a team at University of Texas Southwestern describes the impact of the COVID-19 pandemic on mental health and subsequent increases in body weight among people with obesity. 

Declining Mental Health During COVID-19 Pandemic Linked to Worsening Obesity

An analysis of online survey data from people with type 2 diabetes is providing new insight into patient preferences related to newer oral therapies in 

A custom survey assessing responses to blinded drug profile comparisons comparing empagliflozin 25 mg, oral semaglutide 14 mg, and sitagliptin 100 mg, results of the study provide insight into the most important attributes and most concerning risks pertaining to these newer agents, with results indicating the highest blinded preference score was for the profile matching empagliflozin followed by sitagliptin then oral semaglutide.

“These findings have significant implications as they suggest that patients may be hesitant to initiate guideline-directed medical therapy oral antihyperglycemic therapies with cardiovascular benefit due to side effect concerns,” investigators wrote. “It is possible that these findings reflect a lack of awareness amongst patients of the CV risks associated with T2DM and more focus on side effects and short-term quality of life.”

In recent years, the field of cardiometabolic health has experienced an explosion in knowledge and advancement led primarily by the revelation of the cardiorenal protective benefit provided by some antihyperglycemic agents, such as SGLT2 inhibitors, oral GLP-1 receptor agonists, and DPP-4 inhibitors. However, despite the growing knowledge of these benefits, uptake of these agents has lagged behind, even with inclusion in recent guideline updates.

Led by Gianluigi Savarese, MD, of the Division of Cardiology at Karolinska Institute, and Abhinav Sharma, MD, of the Division of Cardiology at McGill University, the present study was launched with the intent of developing a more thorough understanding of patient preferences related to oral therapies antihyperglycemic agents. With this in mind, investigators designed the current study as an analysis of data from a custom survey distributed to the dQ&A Diabetes Patient Panel, which is a patient panel of more than 15,000 people with type 1 or type 2 diabetes.

Distributed between August 16-23, 2019, investigators received completed surveys from 553 (67.9%) of the 815 patients contacted and issued surveys. Within the survey, participants were presented with hypothetical, blinded, pairwise, drug profile comparison choices, with benefits and harms derived from phase 3 trials for each agent.

Regarding participant characteristics, 25% had an HBa1c of 6.5-7%, 24% had an HbA1c greater than 8%, 26% had a known history of cardiovascular disease, 55% had cardiovascular disease risk only, and 62% were insulin users. Investigators pointed out all demographic and health outcomes data were self-reported, respondents received $10 for participation in surveys, and the median time to completion was 14.5 minutes.

Upon analysis, investigators found genital infection risk was the most important attribute of an agent’s clinical profile (relative score: 19% [z-test, 

=.077]). The next most important attributes from the patient perspective were fasting requirements (15%), weight reduction (15%), risk of vomiting (14%), cardiovascular benefit (12%), and risk of nausea (11%). Investigators highlighted HbA1c and ability to take other medications were considered the most important factor by 8% and 6% of respondents, respectively. When blinded to drug names and dose, 41% of survey respondents chose a profile similar to empagliflozin, 31% chose a profile similar to sitagliptin, 11% chose a profile similar to oral semaglutide, and 17% elected to choose none of the options.

“These results can facilitate broader conversation between patients and clinicians in determining patient-centric therapies, as advised by the American Diabetes Association and European Society of Cardiology guidelines for type 2 diabetes mellitus treatment and may lead to improved compliance and outcomes,” investigators added in their conclusion.

Patient preferences for newer Oral therapies in type 2 diabetes,

An analysis of data from patient surveys provides insight into patient preferences related to oral therapies for type 2 diabetes, with blinded results indicating a preference for SGLT2 inhibitors over oral GLP-1 RA or DPP-4 inhibitors. 

Patient Survey Details Preferences for Newer Oral Therapies in Type 2 Diabetes

A patient in their mid-70s with a history of obesity, hypertension, osteoporosis, and prior ankle surgery presents to the urgent care with right lateral foot pain ongoing for about 10 days. She denies any injury, fever, redness, or other complaints. Pain does not involve her ankle and is minimal at rest but moderate to severe with walking.

Vital signs are normal. A physical exam is also normal except for tenderness to the 5th metatarsal base. There is no appreciable swelling or warmth and pulses are symmetric.

Our latest endocrine case report from Brady Pregerson, MD, features a person in their mid-70s with a history of obesity, hypertension, osteoporosis, and prior ankle surgery presenting to urgent care with right lateral foot pain ongoing for about 10 days. Can you determine the correct diagnosis?

Endocrine Case Report: Foot Pain

A pair of studies released within days of one another have produced conflicting reports related to the apparent increase in 

 diagnoses following a COVID-19 infection in younger patients.

Although one of the studies suggests a COVID-19 infection was associated with up to a 72% increase in new diagnoses of type 1 diabetes, the second, which was presented at the European Association for the Study of Diabetes 2022 annual meeting, purports that while overall rates of diagnoses may be elevated, COVID-19 may not be the cause of increased prevalence.

“Our findings call into question whether a direct association between COVID-19 and new-onset type 1 diabetes in adults and children exists”, said Helen Colhoun, MD, an investigator on the EASD 2022 study and the chair of Medical Informatics and Life Course Epidemiology at the University of Edinburgh,

 “One recent report by researchers at the US CDC, analyzing two large insurance-claim databases of those under age 18, found that children with COVID-19 were 2.5 times as likely to be diagnosed with diabetes over a month after infection than those who were never infected. If replicated, this is going to create a large number of people with newly diagnosed diabetes and might also alter the risk–benefit balance for COVID-19 vaccination in young children. Importantly, we did not confirm that finding.”

Early on in the COVID-19 pandemic, each passing month brought new concerns over comorbidities or the effects of long COVID. Among endocrinologists, the most pressing concern at the height of the pandemic was the risk of severe COVID-19 associated with prediabetes, diabetes, and overweight. Now, that focus has shifted to the long-term health implications for patients, including the potential for increased risk of type 1 diabetes.

The study purporting an increased risk was conducted by Pamela B. Davis, MD, PhD, and colleagues from Case Western Reserve University School of Medicine and the MetroHealth System in Cleveland. An analysis of data from the TriNetX Analytics Platform, investigators created a pair of distinct cohorts for their analyses: one including people 18 years or younger with SARS-CoV-2 infection from March 2020-December 2021 and another including patients of the same age without SARS-CoV-2 infection but with a non-SARS-CoV-2 respiratory infection during the same period. The primary outcome of interest in propensity score-matched analysis was the risk of new diagnoses of type 1 diabetes within 1, 3, and 6 months of COVID_19 infection.

Results of this study suggested the risk of diagnosis of type 1 diabetes was greater among those infected with SARS-CoV-2 compared with those with non–COVID-19 respiratory infection at 1 month (HR, 1.96 [95%CI, 1.26-3.06]), 3 months (HR, 2.10 [95% CI, 1.48-3.00]), and 6 months (HR, 1.83 [95% CI, 1.36-2.44]) after infection.

Although the team of Ohio-based investigators noted further research is needed to further understand any potential links between SARS-CoV-2 infection and new-onset type 1 diabetes, they pushed for heightened awareness surrounding the issue.

“Families with high risk of type 1 diabetes in their children should be especially alert for symptoms of diabetes following COVID, and pediatricians should be alert for an influx of new cases of type 1 diabetes, especially since the Omicron variant of COVID spreads so rapidly among children,” said Davis, the Arline H. and Curtis F. Garvin Research Professor at Case Western University, 

. “We may see a substantial increase in this disease in the coming months to years. Type 1 diabetes is a lifelong challenge for those who have it, and increased incidence represents substantial numbers of children afflicted.”

In the EASD 2022 study, Colhoun and colleagues used linked EHR data from 1,849,411 individuals aged less than 35 years of age without diabetes who tested positive for SARS-CoV-2 and were followed from March 1, 2020-November 22, 2021. The primary outcome of interest for their analyses was risk of incident type 1 diabetes. For the purpose of analysis, investigators planned to compare the trends of incidence observed in the study against those from 2015-2021.

Of the 1.8 million identified for inclusion, a total of 365,080 individuals had at least 1 detected SARS-CoV-2 infection during follow-up and 1074 developed type 1 diabetes. Upon analysis, results indicated the rate ratio for type 1 diabetes associated with a first positive test was 0.86 (95% CI, 0.62-1.21) for infection less than 30 days prior to infection and 2.62 (95% CI, 1.81-3.78) for infection in the previous 30 days. Despite the observed increased in rate ratio, investigators pointed out negative and positive SARS-CoV-2 tests were more frequent in the days surrounding diabetes presentation.

“Our findings show that causes other than COVID-19 infection itself need to be considered in relation to the increased incidence of type 1 diabetes”, said study investigator Professor Paul McKeigue from Public Health Scotland and the University of Edinburgh, in the aforementioned statement from EASD 2022. “We need to consider what has happened regarding the spread of viruses such as enteroviruses during the pandemic, and whether there are any other environmental factors, such as sunlight exposure and vitamin D levels, that might have altered during lockdown that might also be relevant.”

Relation of Incident Type 1 Diabetes to Recent COVID-19 Infection: Cohort Study Using e-Health Record Linkage in Scotland

Association of SARS-CoV-2 Infection With New-Onset Type 1 Diabetes Among Pediatric Patients From 2020 to 2021

A pair of studies published within days of one another provide insight into the apparent increase in risk of type 1 diabetes diagnoses following COVID-19, but one study purports this increase may not be the result of COVID-19. 

Studies Debate Link Between COVID-19 and Increased Type 1 Diabetes Diagnoses

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have announced the release of a new consensus update on the management of hyperglycemia in 

Released on September 23, the 42-page document has a target audience described as the “full spectrum of professional healthcare team providing diabetes care” and provides updates to recommendations made in previous consensus reports from the organizations released in 2018 and 2019.

“We are excited to share an updated consensus report on the management of hyperglycemia in type 2 diabetes,” said Robert Gabbay, MD, PhD, chief scientific and medical officer for the ADA, 

. “This is a wide-ranging consensus report that has several new features. It not only speaks of what needs to be done, but it also has a section on how to implement those changes.”

Led by John Buse, MD, PhD, of the University of North Caroline School of Medicine, and Melanie Davies, CBE, MBChB, MD, of the Leicester Diabetes Centre, the consensus report was composed by a multidisciplinary team of experts representing major institutions from across the US and Europe. A draft version of the report was presented and the opportunity for feedback was provided at the ADA’s 82nd Scientific Session in June 2022. In the aforementioned statement, the ADA press team noted that suggested changes from this feedback period included a greater focus on person-centered care, equity of care, and weight loss management.

Citing more than 340 references, the consensus report was aimed at encapsulating the recent explosion in knowledge and management strategies since the last update was published in 2019. Among the updates highlighted by the ADA were recommendations on use of oral GLP-1 RAs, the GIP/GLP-1 RA class, and combination therapy with GLP-1 RA and insulin. The document also provides information related to glucose-lowering therapies based on the presence of different comorbid conditions.

The document also includes a particular focus on lifestyle modifications and cites a multitude of lifestyle recommendations, including light exercise or resistance training every 30 minutes while sitting, achieving an extra 500 daily steps, reaching the 150-minute threshold of moderate to vigorous physical activity each week, strength training 2-3 times per week, and getting between 6-9 hours of sleep each night.

The entirety of page of 3 of the consensus report is dedicated to a graphic emphasizing the decision cycle for glycemic management in type 2 diabetes, from specific factors that impact treatment choices to ongoing support and monitoring strategies. This is the first of 6 dedicated pages with graphics, chart, or diagrams highlighting specifics aspects of care and diabetes management, including a summary of characteristics for glucose-lowering medications, optimal approaches for holistic person-centered type 2 diabetes management, and recommendations for initiating insulin therapy.

This consensus report, “Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD),” was copublished in 

Released on September 23, the consensus report from the American Diabetes Association and European Association for the Study of Diabetes outlines optimal strategies for management of hyperglycemia in type 2 diabetes—their first update on the subject since 2019. 

American Diabetes Association, EASD Update Recommendations on Hyperglycemia Management in Type 2 Diabetes

Results of the GRADE Study suggest use of GLP-1 receptor agonists and insulin glargine U-100 outperformed sulfonylureas and DPP-4 inhibitors for glycemic control in people with 

Results of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-funded study, which compared the 4 aforementioned classes as add-ons to metformin, indicate use of liraglutide and insulin glargine were associated with a greater ability to help achieve and maintain target glycemic control in people with type 2 diabetes, but no material differences were observed for incidence of microvascular complications or death.

“This study was designed to provide health care providers with important information on how to guide the long-term management of type 2 diabetes,” said Henry Burch, MD, NIDDK’s project scientist for GRADE, 

. “This is an integral step toward precision medicine for diabetes care, as these results can now be used in the decision-making process for each individual patient in light of their levels of glucose control, how well the medications are tolerated, and the person’s other health considerations.”

Launched in 2013, the Glycemic Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study was created with the intent of comparing 4 medications approved by the FDA at the time as add-ons to metformin for improving glycemic control and reducing risk of adverse outcomes. multicenter, parallel-group, comparative effectiveness clinical trial conducted in 36 medical centers in the US, the study followed 5047 participants diagnosed with type 2 diabetes at or after the age of 30 years for a mean of 5.0 years.

Those identified for inclusion were randomized to sitagliptin, liraglutide, glimepiride, or insulin glargine U-100 as add-on therapies to metformin. Overall, the 5047 participants identified for inclusion had a mean age of 57.2±10.0 years, 63.6% were men, and 65.7% identified as White. The mean duration of diabetes at stud entry was 4.2±2.7 years, the mean BMI was 34.3±6.8 kg/m2, and the mean HbA1c was 7.5±0.5%. A total of 1263 received insulin glargine, 1254 received glimepiride, 1262 received liraglutide, and 1268 received sitagliptin. Investigators pointed out thiazolidinediones were not included as a result of safety concerns at the time and SGLT2 inhibitors were not included as they had not yet been approved.

The primary glycemic outcome of interest was achieving an HbA1c of 7.0% or higher and the secondary glycemic outcome of interest was a confirmed HbA1c greater than 7.5%. The GRADE Study Research Group also conducted analyses assessing microvascular and cardiovascular outcomes. Outcomes of interest related to these analyses included hypertension and dyslipidemia, confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml/min/1.73m2 , diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument, major adverse cardiovascular events, and death.

Upon analysis, results suggested there with significant differences in the cumulative incidence of HbA1c levels of 7.0% or greater between the study arms (

 <.001). Incidence rates per 100 patient-years were 26.1, 26.5, 30.4, and 38.1 for liraglutide, insulin glargine, glimepiride, and sitagliptin, respectively. Further analyses indicated these trends persisted when examining the secondary outcome of incidence of an HbA1c level greater than 7.5%. Investigators pointed out no material difference were observed with respect to the primary outcome based on sex, age, or racial/ethnic group.

When examining risk of microvascular and cardiovascular outcomes, results suggested there were no material differences observed for the study’s interventions for the development of hypertension, dyslipidemia, or microvascular outcomes. Investigators noted there was no significant differences in risk of MACE, hospitalization for heart failure, cardiovascular death, or all-cause mortality based on study arm. Investigators highlighted small differences were observed for the rate of cardiovascular disease, with rates of 1.9, 1.9, 1.4, and 2.0 per 100 patient-years in the glargine, glimepiride, liraglutide, and sitagliptin groups, respectively.

“GRADE effectively shows which drugs worked best at achieving and maintaining blood glucose targets over time, but we need to establish even more effective strategies for the long-term maintenance of acceptable glucose levels,” said GRADE study chair David M. Nathan, MD, director of the Massachusetts General Hospital Diabetes Center, Boston, in the aforementioned statement. “We still have more work to do, such as evaluating other interventions and treatment combinations to help people with type 2 diabetes achieve long-term glucose control.”

Glycemia Reduction in Type 2 Diabetes — Microvascular and Cardiovascular Outcomes

Glycemia Reduction in Type 2 Diabetes — Glycemic Outcomes,

Results of the Glycemic Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study provide insight into the comparative effectiveness of DPP-4 inhibitors, GLP-1 RAs, sulfonylureas, and insulin glargine for glycemic control and cardiovascular outcomes in people with type 2 diabetes.

GLP-1 RA, Insulin Glargine Outperform DPP-4 Inhibitors and Sulfonyulreas in GRADE Study 

 globally is expected to double by 2040, according to the results of a new modeling study.

Funded by JDRF International, results of the study project the number of people with type 1 diabetes worldwide to balloon from 8.4 million, which was the 2021 estimate, up to 13.5-17.4 million by 2040, with the largest relative increases occurring in low- and lower-middle-income countries.

“Given that prevalence of people with T1D is projected to increase in all countries to up to 17.5 million cases in 2040, our results provide a warning for substantial negative implications for societies and healthcare systems,”said study investigator Graham Ogle, MBBS, a pediatric endocrinologist with the University of Sydney, in a statement. “There is an opportunity to save millions of lives in the coming decades by raising the standard of care for T1D and increasing awareness of the signs and symptoms of T1D to enable a 100% rate of diagnosis in all countries. Our model, which will be made available open-source, will make data on the burden of T1D widely accessible and serve as a platform for stakeholders to make improvements in T1D care and outcomes.”

Although type 1 diabetes represents a significant threat to life expectancy, notable gaps in data still exist related to prevalence, incidence, and associated mortality for people with type 1 diabetes. With this in mind, Ogle and a team of colleagues fitted a Markov model with data on type 1 diabetes incidence and associate morality for 201 countries for the year of 2021 to estimate project prevalence in 2040.

Overall, investigators obtained data related to the 1 diabetes incidence form 97 countries and mortality data from 37 countries. For the purpose of analysis, diagnosis rates were estimated using data from an expert survey. Additionally, mortality was modeled using random-first regression of published type 1 diabetes mortality data and life expectancy was calculated using life tables. Investigators pointed out estimates were validated against observed prevalence data for 15 countries.

Investigators found the global prevalence of type 1diabetes in 2021 was approximately 8.4 (95% uncertainty interval [UI], 8.1-8.8) million. Of the 8.4 million with diabetes, 18% were less than 20 years of age, 64% were 20-59 years of age, and 19% were aged 60 years or older. During 2021, investigators estimated there were 500,000 new diagnoses of type 1 diabetes, with a median age at onset of 39 years. Results suggest there were about 500,000 undiagnosed cases in 2021 and, during the same time, investigators estimated about 35,000 undiagnosed patients would die within 12 months of symptom onset.

Investigators highlighted 1.8 million individuals with type 1 diabetes were in low-income and lower-middle-income countries. Comparison of life expectancy revealed the life expectancy of a 10-year-old diagnosed with type 1 diabetes in 2021 ranged from a mean of 13 years in low-income countries to 65 years in high-income countries. By 2040, the results of the modeling study pointed to an increase in prevalence to 13.5-17.4 million, which represents an increase of 60-107% over the 2021 figures, with the greatest relative increases observed among low- and lower-middle-income countries.

“Our findings indicate that the overall footprint of T1D is much larger than previous estimates have indicated, when missing prevalence due to excess mortality is accounted for,” said study investigator Kim Donaghue, MBBS, PhD, head of Diabetes Complications Assessment Services Child and Adolescent Health at the University of Sydney, in the aforementioned statement. “This is particularly true in low- and middle-income countries – for example in sub-Saharan Africa which accounts for 357,000 cases of T1D or 4% of global prevalence but 23% of the lives lost each year—highlighting the urgent need to increase awareness of the signs and symptoms of T1D in lower-middle-income countries."

Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study