CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

Therapeutic Inertia and Delays in Insulin Intensification in Type 2 Diabetes: A Literature Review.

Background: Therapeutic inertia leading to delays in insulin initiation or intensification is a major contributor to lack of optimal diabetes care. This report reviews the literature summarizing data on therapeutic inertia and delays in insulin intensification in the management of type 2 diabetes. Methods: A literature search was conducted of the Allied & Complementary Medicine, BIOSIS Previews, Embase, EMCare, International Pharmaceutical Abstracts, MEDLINE, and ToxFile databases for clinical studies, observational research, and meta-analyses from 2012 to 2022 using search terms for type 2 diabetes and delay in initiating/intensifying insulin. Twenty-two studies met inclusion criteria. Results: Time until insulin initiation among patients on two to three antihyperglycemic agents was at least 5 years, and mean A1C ranged from 8.7 to 9.8%. Early insulin intensification was linked with reduced A1C by 1.4%, reduction of severe hypoglycemic events from 4 to <1 per 100 person-years, and diminution in risk of heart failure (HF) by 18%, myocardial infarction (MI) by 23%, and stroke by 28%. In contrast, delayed insulin intensification was associated with increased risk of HF (64%), MI (67%), and stroke (51%) and a higher incidence of diabetic retinopathy. In the views of both patients and providers, hypoglycemia was identified as a primary driver of therapeutic inertia; 75.5% of physicians reported that they would treat more aggressively if not for concerns about hypoglycemia. Conclusion: Long delays before insulin initiation and intensification in clinically eligible patients are largely driven by concerns over hypoglycemia. New diabetes technology that provides continuous glucose monitoring may reduce occurrences of hypoglycemia and help overcome therapeutic inertia associated with insulin initiation and intensification.

Flash Continuous Glucose Monitoring: A Summary Review of Recent Real-World Evidence.

Optimizing glycemic control remains a shared challenge for clinicians and their patients with diabetes. Flash continuous glucose monitoring (CGM) provides immediate information about an individual's current and projected glucose level, allowing users to respond promptly to mitigate or prevent pending hypoglycemia or hyperglycemia. Large randomized controlled trials (RCTs) have demonstrated the glycemic benefits of flash CGM use in both type 1 and type 2 diabetes. However, whereas RCTs are mostly focused on the efficacy of this technology in defined circumstances, real-world studies can assess its effectiveness in wider clinical settings. This review assesses the most recent real-world studies demonstrating the effectiveness of flash CGM use to improve clinical outcomes and health care resource utilization in populations with diabetes.

Addressing the Burden of Multiple Daily Insulin Injections in Type 2 Diabetes with Insulin Pump Technology: A Narrative Review.

The growing prevalence of type 2 diabetes (T2D) remains a leading health concern in the US. Despite new medications and technologies, glycemic control in this population remains suboptimal, which increases the risk of poor outcomes, increased healthcare resource utilization, and associated costs. This article reviews the clinical and economic impacts of suboptimal glycemic control in patients on basal-bolus insulin or multiple daily injections (MDI) and discusses how new technologies, such as tubeless insulin delivery devices, referred to as "patch pumps", have the potential to improve outcomes in patients with T2D.

The Current and Future Role of Insulin Therapy in the Management of Type 2 Diabetes: A Narrative Review.

Early initiation of intensive insulin therapy has been demonstrated to be effective in controlling glycemia and possibly preserving beta-cell function. Innovations in insulin formulations and delivery systems continue. However, we have seen an acceleration in the development of new classes of diabetes medications for individuals with type 2 diabetes and obesity, such as, for example, glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These formulations have been shown to confer significant benefits in achieving good glycemic control with reduced hypoglycemia risk, weight loss, and cardiorenal protection. Therefore, it is reasonable to question whether there is still a role for insulin therapy in the management of type 2 diabetes. However, there are clear limitations inherent to GLP-1 RA therapy, including high rates of suboptimal adherence and treatment discontinuation due to high cost and side effects, which diminish long-term efficacy, and supply issues. In addition, newer formulations have shown improvements in convenience and tolerability, and have been shown to be even more effective when used in conjunction with basal insulin. In this narrative review, we discuss current evidence that supports GLP-1 RA use in combination with insulin therapy and the potential pitfalls of reliance on GLP-1 RAs as a substitute for insulin therapy.

Disparities in prevalence and treatment of diabetes, cardiovascular and chronic kidney diseases - Recommendations from the taskforce of the guideline workshop.

There is a mounting clinical, psychosocial, and socioeconomic burden worldwide as the prevalence of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) continues to rise. Despite the introduction of therapeutic interventions with demonstrated efficacy to prevent the development or progression of these common chronic diseases, many individuals have limited access to these innovations due to their race/ethnicity, and/or socioeconomic status (SES). However, practical guidance to providers and healthcare systems for addressing these disparities is often lacking. In this article, we review the prevalence and impact of healthcare disparities derived from the above-mentioned chronic conditions and present broad-based recommendations for improving access to quality care and health outcomes within the most vulnerable populations.

Continuous Glucose Monitoring Impact and Implications of Real-World Evidence: Past, Present, and Future.

Randomized controlled trials, which are considered the highest level of scientific evidence, have shown significant glycemic benefits associated with use of continuous glucose monitoring (CGM) in individuals with diabetes who are treated with intensive insulin regimens. However, numerous prospective, retrospective, and observational studies have investigated the impact of CGM in various diabetes populations treated with nonintensive therapies. Results from these studies have contributed to changes in payer coverage, prescriber behaviors, and expanding use of CGM. This article reviews findings from recent real-world studies, highlights the key lessons learned from these studies, and discusses how we need to move forward in increasing utilization of and access to CGM among all diabetes patients who would benefit from this technology.

Race/Ethnicity and gender differences in health intentions and behaviors regarding exercise and diet for adults with type 2 diabetes: a cross-sectional analysis.

BACKGROUND: Self-management is the cornerstone of diabetes control and prevention of complications; however, it is undetermined whether differences in intention to adopt healthy lifestyles and actual healthy behavior exist across race/ethnic groups. This study evaluated the differences across racial-ethnic groups in self-reported medical advice received and health intentions and behaviors among adults with type 2 diabetes mellitus. METHODS: A cross-sectional analysis of the 2007 SHIELD US survey ascertained self-reported health intentions and behaviors for regular exercise, diet, and weight management among Non-Hispanic Caucasian (n = 2526), Non-Hispanic African-American (n = 706), and Hispanic (n = 179) respondents with type 2 diabetes. RESULTS: A similar proportion of respondents from each race-gender group (43%-56%) reported receiving healthcare advice to increase their exercise (P = 0.32). Significantly more minorities reported an intention to follow the exercise recommendation compared with Non-Hispanic Caucasians (P = 0.03). More Non-Hispanic African-American (29%) and Hispanic (27%) men reported exercising regularly compared with other race-gender groups (P = 0.02). Significantly more Non-Hispanic Caucasian women (74%) and Hispanic women (79%) reported trying to lose weight compared with other groups (P < 0.0001). CONCLUSIONS: Differences in health intentions and healthy behaviors were noted across race-gender groups. More Non-Hispanic African-American men reported an intention to follow advice on exercising and self-report of exercising regularly was also higher compared with other race-gender groups. More Hispanic men reported high physical activity levels than other groups. Despite an increased willingness to follow healthcare recommendations for diet, >50% of respondents were obese among all race-gender groups.

Treatment of heart failure in African Americans--a call to action.

Advances in heart failure treatment have not necessarily translated into equity in improved outcomes for African Americans. Heart failure in African Americans is characterized by a higher prevalence, especially at younger ages; more-adverse course with more frequent hospitalizations; and higher mortality rates compared to the general population. Despite this distinct disease profile, African Americans are remarkably underrepresented in large heart failure trials. This paper reviews the unique course of heart failure in African Americans and discusses treatment in the context of clinical trial evidence. African Americans with heart failure may respond differently to some standard therapies compared to whites, but low levels of enrollment of AAs in large clinical trials preclude valid conclusions in certain cases. An important exception is the African American Heart Failure Trial (AHeFT), a well-designed, prospective, randomized, placebo-controlled, double-blind study, that added a combination of fixed-dose isosorbide dinitrate/hydralazine (ISDN/ HYD) to standard therapy and showed a 43% improvement in survival and a 33% reduction in first hospitalizations. Despite compelling evidence from AHeFT, post hoc secondary analyses, and recommendations from current practice guidelines, ISDN/HYD remains underutilized in African Americans with heart failure. In this paper, we put forth a call to action for racial equity in clinical research and treatment in African Americans with heart failure.

Real-World Studies Support Use of Continuous Glucose Monitoring in Type 1 and Type 2 Diabetes Independently of Treatment Regimen.

Numerous randomized controlled trials (RCTs) have demonstrated the glycemic benefits of continuous glucose monitoring (CGM) in management of type 1 diabetes (T1D) and type 2 diabetes. Although RCTs remain the gold standard clinical study design, findings from these trials do not necessarily reflect the effectiveness of CGM or reveal the feasibility and wider applications for use in broader real-life settings. This review evaluates recent real-world evidence (RWE) demonstrating the value of CGM to improve clinical outcomes, such as avoidance of severe hypoglycemic and hyperglycemic crises, and improved measures of psychological health and quality of life. Additionally, this review considers recent RWE for the role of CGM to enhance health care resource utilization, including prediction of T1D and applications in gestational diabetes, chronic kidney disease, and monitoring during surgery.

Perceived body image in men and women with type 2 diabetes mellitus: correlation of body mass index with the figure rating scale.

BACKGROUND: Body mass index (BMI) is often used as an objective surrogate estimate of body fat. Increased BMI is directly associated with an increase in metabolic disease, such as type 2 diabetes mellitus (T2DM). The Stunkard Figure Rating Scale (FRS) is a subjective measure of body fat, and self-perceptions of body image conceivably impact the development and treatment of T2DM. This study examined the self-perception of body image to various levels of BMI among those with T2DM. METHODS: Respondents (n = 13,887) to the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) 2006 survey self-reported their weight and height for BMI calculation. On the gender-specific Stunkard FRS, respondents selected the figure most closely resembling their body image. Spearman correlation was computed between perceived body image and BMI for men and women separately. Student's t-test analysis compared the mean BMI differences between respondents with and without T2DM. RESULTS: Men with T2DM did not significantly differ from men without diabetes mellitus in mean BMI per body image figure except at the extremes in body figures. Women with T2DM had a significantly higher BMI for the same body figure compared with women without diabetes mellitus for most figures (p < 0.05). CONCLUSIONS: Individuals, particularly women, with T2DM may differ in their perception of body image compared with those without diabetes mellitus. It is unclear if these perceived differences increase the risk of T2DM, or if the diagnosis of T2DM alters body image perceptions.

Self-Monitoring of Blood Glucose (SMBG) in insulin- and non-insulin-using adults with diabetes: consensus recommendations for improving SMBG accuracy, utilization, and research.

Current clinical guidelines for diabetes care encourage self-monitoring of blood glucose (SMBG) to improve glycemic control. Specific protocols remain variable, however, particularly among non-insulin-using patients. This is due in part to efficacy studies that neglect to consider (1) the performance of monitoring equipment under real-world conditions, (2) whether or how patients have been taught to take action on test results, and (3) the physiological, behavioral, and social circumstances in which SMBG is carried out. As such, a multidisciplinary group of specialists, including several endocrinologists, a health psychologist, a diabetes nurse practitioner, and a patient advocate (the Panel), discuss within this review article how the potential of SMBG might be fully realized in today's healthcare environment. The resulting recommendations cover technological, clinical, behavioral, and research considerations with the aim of achieving short- and long-term benefits, ranging from fewer hypoglycemic episodes to lower complication-related costs. The panel also made suggestions for designing future studies that increase the ability to discern optimal models of SMBG utilization for individuals with diabetes who may, or may not, use insulin.

Approach to Using Trend Arrows in the FreeStyle Libre Flash Glucose Monitoring Systems in Adults.

The use of personal continuous glucose monitoring (CGM) has expanded dramatically among individuals with diabetes. CGM systems provide retrospective data, as well as the current glucose value and trend arrow data, which indicate the direction and velocity of changing glucose. In 2017, Aleppo and colleagues developed a simplified approach for adults with diabetes to safely adjust rapid-acting insulin doses using trend arrow information in the Dexcom G5 CGM system. Since then, the FreeStyle Libre and FreeStyle Libre 14-day CGM systems have become available in the United States; however, guidance on using trend arrow data that take the unique features of these systems into consideration is lacking. Specifically, the FreeStyle Libre systems do not have automatic alarms, which impact how the system and trend arrow data are used. The Endocrine Society convened an expert panel to address this gap and develop an approach to adjusting rapid-acting insulin doses for adults using trend arrows in the FreeStyle Libre systems. We based our approach on previous work and expanded upon engagement and scanning recommendations, and we incorporated pre-exercise planning specific to these systems. Our approach provides insulin dose adjustments as discrete insulin units based on an individual's insulin sensitivity and directionality of the trend arrow. We focus on the needs of patients treated with multiple daily injections because these individuals currently make up a greater proportion of individuals on intensive insulin therapy. Our recommendations are intended to provide a safe, practical approach to using trend arrows in the FreeStyle Libre systems.

The Berlin Declaration: A call to improve early actions related to type 2 diabetes. Why is primary care important?

Diabetes is epidemic worldwide and places a huge burden on healthcare systems. The majority of the cost of type 2 diabetes (T2D) is related to hospitalization and the management of complications, and these also have a negative impact on the individual's quality of life. The Berlin Declaration is a global call for early action for the identification of high risk individuals, prevention of T2D and the prevention of complications in those with T2D, through prevention, early detection, early control and early access to the right multidisciplinary interventions. This should empower people to take action to prevent T2D and its complications.

The Berlin Declaration: A call to action to improve early actions related to type 2 diabetes. How can specialist care help?

Diabetes is a major global epidemic and places a huge burden on healthcare systems worldwide. The complications of type 2 diabetes (T2D) and related hospitalizations are major contributors to this burden, and there is strong evidence that the risk for these can be reduced by early action to identify and prevent progression of people at high risk of T2D and ensure tight glycemic control in those with established disease. In response to this, the Berlin Declaration was developed by four working groups of experts and ratified by healthcare professionals from 38 countries. Its aim is to act as a global call to action for early intervention in diabetes, in addition to providing short-, medium- and long-term targets that should be relevant to all nations. The Berlin Declaration focuses on four aspects of early action, and proposes actionable policies relating to each aspect: early detection, prevention, early control and early access to the right interventions. In addition, a number of treatment targets are proposed to provide goals for these policies. To ensure that the suggested policies are enacted in the most effective manner, the support of specialist care professionals is considered essential.

Prevalence of self-reported diagnosis of diabetes mellitus and associated risk factors in a national survey in the US population: SHIELD (Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes).

BACKGROUND: Studies derived from continuous national surveys have shown that the prevalence of diagnosed diabetes mellitus in the US is increasing. This study estimated the prevalence in 2004 of self-reported diagnosis of diabetes and other conditions in a community-based population, using data from the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD). METHODS: The initial screening questionnaire was mailed in 2004 to a stratified random sample of 200,000 households in the US, to identify individuals, age > or = 18 years of age, with diabetes or risk factors associated with diabetes. Follow-up disease impact questionnaires were then mailed to a representative, stratified random sample of individuals (n = 22,001) in each subgroup of interest (those with diabetes or different numbers of risk factors for diabetes). Estimated national prevalence of diabetes and other conditions was calculated, and compared to prevalence estimates from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. RESULTS: Response rates were 63.7% for the screening, and 71.8% for the follow-up baseline survey. The SHIELD screening survey found overall prevalence of self-reported diagnosis of diabetes (either type 1 or type 2) was 8.2%, with increased prevalence with increasing age and decreasing income. In logistic regression modeling, individuals were more likely to be diagnosed with type 2 diabetes if they had abdominal obesity (odds ratio [OR] = 3.50; p < 0.0001), BMI > or =28 kg/m2 (OR = 4.04; p < 0.0001), or had been diagnosed with dyslipidemia (OR = 3.95; p < 0.0001), hypertension (OR = 4.82; p < 0.0001), or with cardiovascular disease (OR = 3.38; p < 0.0001). CONCLUSION: The SHIELD design allowed for a very large, community-based sample with broad demographic representation of the population of interest. When comparing results from the SHIELD screening survey (self-report only) to those from NHANES 1999-2002 (self-report, clinical and laboratory evaluations), the prevalence of diabetes was similar. SHIELD allows the identification of respondents with and without a current diagnosis of the illness of interest, and potential longitudinal evaluation of risk factors for future diagnosis of that illness.

Guidelines for management of high-risk African Americans with multiple cardiovascular risk factors: recommendations of an expert consensus panel.

African Americans have higher rates of cardiovascular disease (CVD) than do Caucasians, which contributes significantly to their reduced life expectancy. Most African American adults have at least one major risk factor for CVD. Nonetheless, African Americans are often underdiagnosed and undertreated, despite presenting to the healthcare system late in their course, often after a CVD event. Patients with multiple risk factors have a CVD risk far greater than the sum of their individual risks. Metabolic syndrome tends to be clustered to a greater degree in African American women. Aggressive management of African Americans is necessary. In this report, we provide guidelines for the management of high-risk African Americans. For each individual risk factor, we address existing data and guidelines in the general population, existing data in African Americans, and proposed guidelines for African Americans based on evidence or extrapolation. In particular, for elevated cholesterol and blood pressure, evidence is emerging that lower is better, so aggressive management strategies are necessary. For dyslipidemia, statins alone will generally reach the goal, but for hypertension, multiple drugs are usually necessary. We conclude that further research in African Americans is necessary to complete the totality of evidence.