Cardiovascular Outcomes with Once-Weekly GLP-1 RAs: Clinical and Economic Implications.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects. Given these benefits, there has been substantial interest in evaluating the cardiovascular safety of GLP-1 RAs as well as their potential to reduce the risk of major adverse cardiac events (MACE). Following the superior clinical outcome with the once-daily GLP-1 RA liraglutide (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results [LEADER]), this review examines and summarizes the effects of once-weekly GLP-1 RAs, including exenatide extended release (ER), dulaglutide, and semaglutide, on reducing cardiovascular events in patients with T2DM. A phase 3 cardiovascular outcomes trial (EXSCEL) of exenatide ER found no significant difference between exenatide ER and placebo in reducing MACE in patients with T2DM. In a phase 3 premarketing trial in T2DM patients at high risk of cardiovascular disease (SUSTAIN-6), semaglutide significantly reduced the risks of MACE and non-fatal stroke compared with placebo. A phase 3 study (REWIND) is underway to evaluate the effects of dulaglutide on MACE. Considering the substantial costs of cardiovascular disease in patients with T2DM, it will be of interest to assess the impact of treatment with once-weekly GLP-1 RAs on cardiovascular disease-related costs among patients with T2DM. DISCLOSURES: This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose.

Adherence to thyroid hormone replacement therapy: a retrospective, claims database analysis.

OBJECTIVE: The objective of this analysis was to compare adherence at 6 months and 12 months across levothyroxine formulations for patients with hypothyroidism. METHODS: This retrospective analysis utilized insurance claims data from a commercially insured population from January 1, 2000 through March 31, 2016. Patients were included if they were diagnosed with hypothyroidism and initiated treatment with generic levothyroxine, Levoxyl, Synthroid, Unithroid, or Tirosint. Patients were excluded if they were younger than age 18, were diagnosed with thyroid cancer, received a prescription for liothyronine, or did not have continuous insurance coverage over the study period. Adherence, defined by the proportion of days covered (PDC) ≥ 80%, was examined using multivariable analyses for both 6 and 12 months post-initiation on therapy Results: The study identified 580,331 patients who fit the study criteria. At 6 months, 40.3% of patients were found to be non-adherent, while 51.9% were non-adherent at 12 months. Synthroid was associated with significantly higher adherence compared to all other levothyroxine formulations at both 6 and 12 months. Compared to generic levothyroxine, the likelihood of being adherent at 12 months was highest for Synthroid (OR = 1.44; 95% CI = 1.43-1.46), followed by Levoxyl (OR = 1.20 95% CI = 1.17-1.23). Tirosint and Unithroid were associated with significantly lower adherence at 12 months compared to generic levothyroxine (OR = 0.65; 95% CI = 0.57-0.75 and OR = 0.79; 95% CI = 0.71-0.89, respectively). CONCLUSIONS: This large, retrospective real-world study demonstrated that adherence to levothyroxine remains a concern among patients with hypothyroidism, and that differences in adherence may exist across levothyroxine formulations.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE - EXECUTIVE SUMMARYComplete Appendix to Guidelines available at http://journals.aace.com.

OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Each Recommendation is based on a diligent review of the clinical evidence with transparent incorporation of subjective factors. RESULTS: The Executive Summary of this document contains 87 Recommendations of which 45 are Grade A (51.7%), 18 are Grade B (20.7%), 15 are Grade C (17.2%), and 9 (10.3%) are Grade D. These detailed, evidence-based recommendations allow for nuance-based clinical decision making that addresses multiple aspects of real-world medical care. The evidence base presented in the subsequent Appendix provides relevant supporting information for Executive Summary Recommendations. This update contains 695 citations of which 202 (29.1 %) are evidence level (EL) 1 (strong), 137 (19.7%) are EL 2 (intermediate), 119 (17.1%) are EL 3 (weak), and 237 (34.1%) are EL 4 (no clinical evidence). CONCLUSION: This CPG is a practical tool that endocrinologists, other healthcare professionals, regulatory bodies and health-related organizations can use to reduce the risks and consequences of dyslipidemia. It provides guidance on screening, risk assessment, and treatment recommendations for a range of patients with various lipid disorders. These recommendations emphasize the importance of treating low-density lipoprotein cholesterol (LDL-C) in some individuals to lower goals than previously recommended and support the measurement of coronary artery calcium scores and inflammatory markers to help stratify risk. Special consideration is given to patients with diabetes, familial hypercholesterolemia, women, and pediatric patients with dyslipidemia. Both clinical and cost-effectiveness data are provided to support treatment decisions. ABBREVIATIONS: A1C = hemoglobin A1C ACE = American College of Endocrinology ACS = acute coronary syndrome AHA = American Heart Association ASCVD = atherosclerotic cardiovascular disease ATP = Adult Treatment Panel apo = apolipoprotein BEL = best evidence level CKD = chronic kidney disease CPG = clinical practice guidelines CVA = cerebrovascular accident EL = evidence level FH = familial hypercholesterolemia HDL-C = high-density lipoprotein cholesterol HeFH = heterozygous familial hypercholesterolemia HIV = human immunodeficiency virus HoFH = homozygous familial hypercholesterolemia hsCRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol Lp-PLA2 = lipoprotein-associated phospholipase A2 MESA = Multi-Ethnic Study of Atherosclerosis MetS = metabolic syndrome MI = myocardial infarction NCEP = National Cholesterol Education Program PCOS = polycystic ovary syndrome PCSK9 = proprotein convertase subtilisin/kexin type 9 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus TG = triglycerides VLDL-C = very low-density lipoprotein cholesterol.

Information technology for the treatment of diabetes: improving outcomes and controlling costs.

BACKGROUND: Diabetes in particular presents an ideal opportunity for the incorporation of information technology (IT) in the provision of care. The disease is highly prevalent in managed care populations, is frequently associated with comorbid conditions, and requires multiple medications in its management. Furthermore, effective diabetes care involves the monitoring of several measures of disease control, such as hemoglobin A1c (A1c) and lipid levels, by several different levels of providers, such as physicians, nurse practitioners, physician assistants, pharmacists, and dieticians. All of these factors combined make diabetes an opportune disease state for a case study of the implementation of health information technology (HIT) in managed care. OBJECTIVE: To review practical applications of HIT for improving the delivery of care in diabetes management. SUMMARY: Between 1990 and 2002, the incidence of type 2 diabetes increased by 61% in the United States. The total costs associated with diabetes have been increasing since the late 1970s as well, with a more dramatic rise over the last 10 years. In fact, the total cost of diabetes in the United States will approach $200 billion per year by the year 2020. In order to improve diabetes management efforts nation wide, the goal of glucose lowering therapy has been recommended to lower the hemoglobin A1c (A1c) to < 7% and keep it below that level long term. Other measures beyond A1c levels have also been identified as being important components to effective diabetes management and incorporated into national treatment recommendations, providing an ideal opportunity for the incorporation of HIT interventions. These interventions have been aimed at 3 different groups of stakeholders in managed care: payers, providers, and patients. CONCLUSIONS: While uncontrolled diabetes remains a major concern in managed care from both a health and a cost perspective, implementation of information technology enabled diabetes management (ITDM) has demonstrated significant potential for improving processes of care, preventing the development of diabetic complications, and generating cost savings. ITDM improves the synthesis of information, the delivery of knowledge, and the efficiency of communication, allowing for coordination of care across delivery teams. Of the existing technologies targeting providers, patients, and payers, provider centered interventions, such as diabetes registries currently show the most potential for benefit in improving outcomes and reducing costs.