Randomized Evaluation of a Remote Management Program to Improve Guideline-Directed Medical Therapy: The DRIVE Trial.

BACKGROUND: Several SGLT2i (sodium-glucose transport protein 2 inhibitors) and GLP1-RA (glucagon-like peptide-1 receptor agonists) reduce cardiovascular events and improve kidney outcomes in patients with type 2 diabetes; however, utilization remains low despite guideline recommendations. METHODS: A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with type 2 diabetes with increased cardiovascular or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP1-RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP1-RA (ie, Simultaneous) or 2 months of virtual education followed by medication prescription (ie, Education-First) delivered by a multidisciplinary team driven by nonlicensed navigators and clinical pharmacists who prescribed SGLT2i or GLP1-RA using a standardized treatment algorithm. The primary outcome was the proportion of patients with prescriptions for either SGLT2i or GLP1-RA by 6 months. RESULTS: Between March 2021 and December 2022, 200 patients were randomized. The mean age was 66.5 years; 36.5% were female, and 22.0% were non-White. Overall, 30.0% had cardiovascular disease, 5.0% had cerebrovascular disease, and 1.5% had both. Mean estimated glomerular filtration rate was 77.9 mL/(min‧1.73 m2), and mean urine/albumin creatinine ratio was 88.6 mg/g. After 2 months, 69 of 200 (34.5%) patients received a new prescription for either SGLT2i or GLP1-RA: 53.4% of patients in the Simultaneous arm and 8.3% of patients in the Education-First arm (P<0.001). After 6 months, 128 of 200 (64.0%) received a new prescription: 69.8% of patients in the Simultaneous arm and 56.0% of patients in Education-First (P<0.001). Patient self-report of taking SGLT2i or GLP1-RA within 6 months of trial entry was similarly greater in the Simultaneous versus Education-First arm (69 of 116 [59.5%] versus 37 of 84 [44.0%]; P<0.001) Median time to first prescription was 24 (interquartile range [IQR], 13-50) versus 85 days (IQR, 65-106), respectively (P<0.001). CONCLUSIONS: In this randomized trial, a remote, team-based program identifies patients with type 2 diabetes and high cardiovascular or kidney risk, provides virtual education, prescribes SGLT2i or GLP1-RA, and improves guideline-directed medical therapy. These findings support greater utilization of virtual team-based approaches to optimize chronic disease management. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06046560.

Methods, rationale, and design for a remote pharmacist and navigator-driven disease management program to improve guideline-directed medical therapy in patients with type 2 diabetes at elevated cardiovascular and/or kidney risk.

AIM: Describe the rationale for and design of Diabetes Remote Intervention to improVe use of Evidence-based medications (DRIVE), a remote medication management program designed to initiate and titrate guideline-directed medical therapy (GDMT) in patients with type 2 diabetes (T2D) at elevated cardiovascular (CV) and/or kidney risk by leveraging non-physician providers. METHODS: An electronic health record based algorithm is used to identify patients with T2D and either established atherosclerotic CV disease (ASCVD), high risk for ASCVD, chronic kidney disease, and/or heart failure within our health system. Patients are invited to participate and randomly assigned to either simultaneous education and medication management, or a period of education prior to medication management. Patient navigators (trained, non-licensed staff) are the primary points of contact while a pharmacist or nurse practitioner reviews and authorizes each medication initiation and titration under an institution-approved collaborative drug therapy management protocol with supervision from a cardiologist and/or endocrinologist. Patient engagement is managed through software to support communication, automation, workflow, and standardization. CONCLUSION: We are testing a remote, navigator-driven, pharmacist-led, and physician-overseen management strategy to optimize GDMT for T2D as a population-level strategy to close the gap between guidelines and clinical practice for patients with T2D at elevated CV and/or kidney risk.

Assessment of Sex Disparities in Nonacceptance of Statin Therapy and Low-Density Lipoprotein Cholesterol Levels Among Patients at High Cardiovascular Risk.

Importance: Many patients at high cardiovascular risk-women more commonly than men-are not receiving statins. Anecdotally, it is common for patients to not accept statin therapy recommendations by their clinicians. However, population-based data on nonacceptance of statin therapy by patients are lacking. Objectives: To evaluate sex disparities in nonacceptance of statin therapy and assess their association with low-density lipoprotein (LDL) cholesterol control. Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 2019, to December 31, 2022, of statin-naive patients with atherosclerotic cardiovascular disease, diabetes, or LDL cholesterol levels of 190 mg/dL (to convert to millimoles per liter, multiply by 0.0259) or more who were treated at Mass General Brigham between January 1, 2000, and December 31, 2018. Exposure: Recommendation of statin therapy by the patient's clinician, ascertained from the combination of electronic health record prescription data and natural language processing of electronic clinician notes. Main Outcomes and Measures: Time to achieve an LDL cholesterol level of less than 100 mg/dL. Results: Of 24 212 study patients (mean [SD] age, 58.8 [13.0] years; 12 294 women [50.8%]), 5308 (21.9%) did not accept the initial recommendation of statin therapy. Nonacceptance of statin therapy was more common among women than men (24.1% [2957 of 12 294] vs 19.7% [2351 of 11 918]; P < .001) and was similarly higher in every subgroup in the analysis stratified by comorbidities. In multivariable analysis, female sex was associated with lower odds of statin therapy acceptance (0.82 [95% CI, 0.78-0.88]). Patients who did vs did not accept a statin therapy recommendation achieved an LDL cholesterol level of less than 100 mg/dL over a median of 1.5 years (IQR, 0.4-5.5 years) vs 4.4 years (IQR, 1.3-11.1 years) (P < .001). In a multivariable analysis adjusted for demographic characteristics and comorbidities, nonacceptance of statin therapy was associated with a longer time to achieve an LDL cholesterol level of less than 100 mg/dL (hazard ratio, 0.57 [95% CI, 0.55-0.60]). Conclusions and Relevance: This cohort study suggests that nonacceptance of a statin therapy recommendation was common among patients at high cardiovascular risk and was particularly common among women. It was associated with significantly higher LDL cholesterol levels, potentially increasing the risk for cardiovascular events. Further research is needed to understand the reasons for nonacceptance of statin therapy by patients and to develop methods to ensure that all patients receive optimal therapy in accordance with their preferences and priorities.

Asymptomatic Diabetic Cardiomyopathy: an Underrecognized Entity in Type 2 Diabetes.

PURPOSE OF REVIEW: Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with diabetic cardiomyopathy (DbCM) referring to abnormal heart structure in the absence of other driving cardiac factors such as hypertension, coronary artery disease (CAD), and valvular heart disease. Stage B DbCM is commonly asymptomatic and represents a form of stage B HF; DbCM thus represents a transitional phenotype prior to onset of symptomatic HF. The pathogenesis of DbCM is not fully elucidated but involves hyperglycemia, insulin resistance, increased free fatty acids (FFA), lipotoxicity, oxidative stress, advanced glycation end product (AGE) formation, activation of the renin-angiotensin-aldosterone system (RAAS) with an increase in angiotensin II, and dyshomeostasis of calcium, which all contribute to left ventricular hypertrophy (LVH) and cardiac systolic and diastolic dysfunction. Although DbCM is an established pathogenic process, it is underrecognized clinically due to its commonly asymptomatic nature. Raising awareness to identify high-risk individuals with stage B HF due to DbCM, who may subsequently progress to overt HF (stage C/D HF), as well as identifying new pharmacological agents and approaches to prevent functional decline, may help reduce this global health problem. The aim of this review is to focus on stage B DbCM; provide data on diagnostic approaches, current therapies, and potential therapies under investigation; and highlight the need to raise awareness and interdisciplinary dialogue among clinicians and researchers. RECENT FINDINGS: There are no currently approved therapeutic strategies to treat or prevent progression of stage B DbCM, but multiple attempts are being made to target different pathogenic mechanisms involved in the development of DbCM. Recent cardiovascular (CV) outcome trials (CVOTs) have identified newer therapeutic agents with CV benefit, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors that reduce hospitalization for HF and glucagon-like peptide-1 (GLP-1) receptor agonists that reduce major adverse CV events (MACE), though without consistent effect on HF outcomes. Recent clinical practice guidelines recommend screening patients at high risk for HF. Further definition and interdisciplinary discussion of high-yield populations to screen, appropriate subsequent evaluation and intervention are needed to advance this area. DbCM is a complex entity that results from multiple pathogenic mechanisms triggered by impairment of glucose and lipid metabolism over many years. DbCM is commonly asymptomatic and represents a form of stage B HF. It is an underrecognized process that may progress to functional decline and overt HF. Although newer medications approved for the treatment of T2D may play an important role in reducing the risk of HF complications, less focus has been placed on earlier recognition and treatment of DbCM while asymptomatic. Additional efforts should be made to further study and target this stage in order to decrease the overall burden of HF.

Patient-provider discussions of bariatric surgery and subsequent weight changes and receipt of bariatric surgery.

OBJECTIVE: The purpose of this study was to determine whether patients who discuss bariatric surgery with their providers are more likely to undergo the procedure and to lose weight. METHODS: A retrospective cohort study of adults with BMI ≥ 35 kg/m2 treated between 2000 and 2015 was conducted to analyze the relationship between a discussion of bariatric surgery in the first year after study entry and weight changes (primary outcome) and receipt of bariatric surgery (secondary outcome) over 2 years after study entry. Natural language processing was used to identify the documentation of bariatric surgery discussion in electronic provider notes. RESULTS: Out of 30,560 study patients, a total of 2,659 (8.7%) discussed bariatric surgery with their providers. The BMI of patients who discussed bariatric surgery decreased by 2.18 versus 0.21 for patients who did not (p < 0.001). In a multivariable analysis, patients who discussed bariatric surgery with their providers lost more weight (by 1.43 [change in BMI]; 95% CI: 1.29-1.57) and had greater odds (10.2; 95% CI: 9.0-11.6; p < 0.001) of undergoing bariatric surgery. CONCLUSIONS: Clinicians rarely discussed bariatric surgery with their patients. Patients who did have this discussion were more likely to lose weight and to undergo bariatric surgery.

Coexistence of Immune Checkpoint Inhibitor-Induced Autoimmune Diabetes and Pancreatitis.

Autoimmune diabetes is a rare but severe endocrine toxicity induced by immune checkpoint inhibitor (ICI) treatment. It is unclear if ICI causes selective islet toxicity or non-selective pancreas toxicity. We analyzed 11 patients treated with ICI who developed ICI-related autoimmune diabetes. Eight patients had lipase and/or amylase tested on the same day of diagnosis of autoimmune diabetes. Among them, 75% (6/8) had normal lipase and 100% (6/6) had normal amylase. There was no correlation between glucose level at onset and biochemical pancreatitis. We characterized the clinical features of ICI-induced autoimmune diabetes. Fifty-five percent (6/11) of patients tested positive for GAD65 autoantibodies, and 55% (6/11) developed diabetic ketoacidosis at manifestation of hyperglycemia. In all 11 patients, C-peptide levels were low in the presence of hyperglycemia. ICI-induced thyroiditis was found in 64% (7/11), of which 36% (4/11) were newly diagnosed with thyroiditis while the remaining 27% (3/11) had pre-existing hypothyroidism followed by ICI-induced thyroiditis. Additionally, 27% (3/11), developed ICI-induced hypophysitis. Thyroiditis and autoimmune diabetes coexisted in all patients with ICI-induced hypophysitis. The median time from ICI treatment to the onset of autoimmune diabetes was 11 weeks. Our data suggest that few patients had coexistent ICI-induced autoimmune diabetes and pancreatitis, suggesting ICI mainly caused selective islet toxicity.

Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review.

Importance: Recent randomized clinical trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce cardiovascular events in at-risk individuals with type 2 diabetes. Despite these findings, GLP-1RAs are underused in eligible patients, particularly by cardiologists. Observations: To date, randomized clinical trials of albiglutide, dulaglutide, liraglutide, and injectable semaglutide have reported favorable cardiovascular outcomes. Most recently approved for clinical use, oral semaglutide has a favorable safety profile and is currently undergoing regulatory evaluation and further study for cardiovascular outcomes. Professional society guidelines now recommend GLP-1RA therapy for cardiovascular risk mitigation in patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors, independent of glucose control or background antihyperglycemic therapy (other diabetes medications being used). Additional conditions suitable for GLP-1RA therapy include obesity and advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), for which cardiovascular risk-reducing options are limited. Out-of-pocket costs and secondary advantages (eg, weight loss) may inform shared decision-making discussions regarding potential therapies. GLP-1RA therapy has a favorable safety profile. Its most common adverse effect is gastrointestinal upset, which typically wanes during the early weeks of therapy and may be mitigated by starting at the lowest dose and escalating as tolerated. Depending on baseline glycemic control, sulfonylureas and insulin may need to be decreased before GLP-1RA initiation; without concurrent use of insulin or sulfonylureas, GLP-1RAs are not associated with hypoglycemia. Multidisciplinary follow-up and collaborative care with primary care physicians and/or endocrinologists are important. Conclusions and Relevance: Findings from this review suggest that GLP-1RAs are safe, are well tolerated, and improve cardiovascular outcomes, largely independent of their antihyperglycemic properties, but they remain underused by cardiologists. This review provides a practical resource for cardiologists for initiating GLP-1RAs and managing the therapy in patients with type 2 diabetes and established ASCVD or high risk for ASCVD.

Bridging the Gap for Patients with Diabetes and Cardiovascular Disease Through Cardiometabolic Collaboration.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with type 2 diabetes (T2D). Recent cardiovascular outcome trials (CVOTs) have established sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1 RA) as powerful medications that can lower glucose as well as reduce the risk of complications of CVD in many individuals with T2D. The combination of glycemic and cardiovascular benefits of SGLT2i and GLP1 RA has highlighted the importance of collaborative care of patients by diabetes and cardiovascular specialists. We review several models of cardiometabolic care for patients with diabetes and CVD and discuss practical ways in which diabetes and cardiovascular specialists can work together to improve cardiometabolic care. RECENT FINDINGS: CVOTs for SGLT2i and GLP1 RA have demonstrated a significant reduction in major adverse cardiovascular events in individuals with T2D and CVD, in addition to their beneficial effects on glucose lowering and weight loss. Additionally, several models of care, including population health screening models with or without a remote management intervention, multidisciplinary clinics, and combined cardiometabolic training, have been proposed to better facilitate the multifaceted care that individuals with diabetes and CVD require. Innovative models of cardiometabolic care have the potential to improve the quality of care that individuals with diabetes and CVD receive. Through collaboration and co-management, diabetes specialists, cardiovascular specialists, and primary care providers have the ability to optimize diabetes and cardiovascular care.

Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints.

Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) with inhibitory antibodies has demonstrated effective and durable antitumor activity in subgroups of patients with cancer. The US Food and Drug Administration has approved several immune checkpoint inhibitors (ICPis) for the treatment of a broad spectrum of malignancies. Endocrinopathies have emerged as one of the most common immune-related adverse events (irAEs) of ICPi therapy. Hypophysitis, thyroid dysfunction, insulin-deficient diabetes mellitus, and primary adrenal insufficiency have been reported as irAEs due to ICPi therapy. Hypophysitis is particularly associated with anti-CTLA-4 therapy, whereas thyroid dysfunction is particularly associated with anti-PD-1 therapy. Diabetes mellitus and primary adrenal insufficiency are rare endocrine toxicities associated with ICPi therapy but can be life-threatening if not promptly recognized and treated. Notably, combination anti-CTLA-4 and anti-PD-1 therapy is associated with the highest incidence of ICPi-related endocrinopathies. The precise mechanisms underlying these endocrine irAEs remain to be elucidated. Most ICPi-related endocrinopathies occur within 12 weeks after the initiation of ICPi therapy, but several have been reported to develop several months to years after ICPi initiation. Some ICPi-related endocrinopathies may resolve spontaneously, but others, such as central adrenal insufficiency and primary hypothyroidism, appear to be persistent in most cases. The mainstay of management of ICPi-related endocrinopathies is hormone replacement and symptom control. Further studies are needed to determine (i) whether high-dose corticosteroids in the treatment of ICPi-related endocrinopathies preserves endocrine function (especially in hypophysitis), and (ii) whether the development of ICPi-related endocrinopathies correlates with tumor response to ICPi therapy.

Extracting Healthcare Quality Information from Unstructured Data.

Healthcare quality research is a fundamental task that involves assessing treatment patterns and measuring the associated patient outcomes to identify potential areas for improving healthcare. While both qualitative and quantitative approaches are used, a major obstacle for the quantitative approach is that many useful healthcare quality indicators are buried within provider narrative notes, requiring expensive and laborious manual chart review to identify and measure them. Information extraction is a key Natural Language Processing (NLP) task for discovering and mining critical knowledge buried in unstructured clinical data. Nevertheless, widespread adoption of NLP has yet to materialize; the technical skills required for the development or use of such software present a major barrier for medical researchers wishing to employ these methods. In this paper we introduce Canary, a free and open source solution designed for users without NLP and technical expertise and apply it to four tasks, aiming to measure the frequency of: (1) insulin decline; (2) statin medication decline; (3) adverse reactions to statins; and (3) bariatric surgery counselling. Our results demonstrate that this approach facilitates mining of unstructured data with high accuracy, enabling the extraction of actionable healthcare quality insights from free-text data sources.