Standards of Diabetes 2019 Medical Care in Diabetes 2019 - PDF document

6/13/2019 Practical Application of the Updated American Diabetes Association (ADA) Standards of Medical Care in Standards of Diabetes – 2019 Medical Care in Diabetes – 2019 Presented by Ron Scott, R.Ph, Ph.C. 06/22/2019 1 2 Background Outline • Recent clinical trials that lay the foundation • Meeting in Berlin, Oct 2018 (Input since June) for new recommendations • Simultaneously published in Diabetes Care and • Decision cycle for DM management Diabetologia • Consensus recommendations from ADA/EASD • Update to prior position statements in 2012 and • Graphics/Algorithms for medication choices 2015 • 479 (English) papers evaluated (pub since 2014) • Emerging technologies, key knowledge gaps, • Incorporated into ADA Standards of Practice new and enduring questions • Central Theme: Decision Cycle for DM management • Discussion 3 4 Key Takeaways Rationale • For weight: Weight loss, lifestyle, medication, and • Summarize large body of recent evidence surgical intervention are all recommended • ASCVD is the leading cause of death with DM2 • For clinical CVD (Cardiovascular disease): SGLT-2 or • Diabetes self-management education and support GLP-1 with proven CV benefit are recommended (DSMES) is fundamental to DM2 care • For CKD (Chronic Kidney Disease) or clinical HF (Heart • Comprehensive implementation of evidence-based Failure) (esp w/ASCVD (Atherosclerotic CVD)): SGLT- interventions has been key to significant reduction of 2 with proven benefit is recommended • GLP-1 is generally recommended as the first ASCVD events and mortality over past few decades • ASCVD, HF, CKD affect 15-25% of DM patients injectable medication • Assess CV status first 5 6 1

6/13/2019 Care Delivery Systems. Classification. Diabetes can be classified into the following general categories: • 33-49% of patients still do not meet targets for 1. Type 1 diabetes (due to autoimmune ß-cell destruction, usually A1C, blood pressure, or lipids leading to absolute insulin deficiency) • Only14% of patients meet targets for all A1C, BP, 2. Type 2 diabetes (due to a progressive loss of ß-cell insulin secretion frequently on the background of insulin resistance) lipids, and nonsmoking status 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the • Progress in CVD risk factor control is slowing second or third trimester of pregnancy that was not clearly overt • System-level improvements are needed diabetes prior to gestation) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity- onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), and drug- or chemical-induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AIDS, or after organ transplantation) Improving Care and Promoting Health in Populations: Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes - 2019 . Diabetes Care 2019;42(Suppl. Standards of Medical Care in Diabetes - 2019 . Diabetes Care 2019;42(Suppl. 1):S7-S12 1):S13-S28 7 8 Definition of ASCVD and MACE Recent GLP-1 Studies of Note • ASCVD is defined somewhat differently across trials LEADER trial • All of the outcomes trials discussed today enrolled • Liraglutide, studied in the Liraglutide Effect and Action in individuals with established CVD (e.g. myocardial Diabetes: Evaluation of Cardiovascular Outcomes Results infarction [MI], stroke, any revascularization (LEADER) trial (n = 9340) procedure). • ARR of 1.9% with an HR of 0.87 (p = 0.01 for superiority) for primary outcome of MACE compared with placebo • They variably included related conditions like TIA, over 3.8 years. unstable angina, amputation, CHF, >50% stenosis of • Each component of the composite contributed to the any artery, coronary artery disease, CKD benefit. HR for cardiovascular death was 0.78 (p = 0.007; ARR 1.7%). HR for all-cause mortality was 0.85 (p = 0.02; • Major adverse cardiac events [MACE]: Cardiovascular ARR 1.4%). death, non-fatal MI and non-fatal stroke 9 10 Recent GLP-1 Studies of Note Recent Studies of Note SUSTAIN 6 trial EXSCEL trial • Semaglutide, studied in the Trial to Evaluate • Exenatide, studied in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial (n=14,752) Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes • Compared exenatide ER with placebo over 3.2 years. (SUSTAIN 6) (n = 3297) Exenatide was safe (non-inferior). • Compared with placebo demonstrated an ARR of • HR for MACE in the entire trial was 0.91 (p = 0.06), not 2.3% with HR 0.74 for MACE (p = 0.02 for superiority) demonstrating statistical superiority. ARR was 0.8%. over 2.1 years • All-cause death was lower in the exenatide arm (ARR 1%, • Reduction in events appeared to be driven by the HR 0.86, but also not statistically significant. rate of stroke, rather than CVD death 11 12 2

6/13/2019 Recent GLP-1 Studies of Note Recent SGLT-2 Studies of Note EMPA-REG OUTCOME trial • Lixisenatide, a short-acting GLP-1, did not demonstrate • Empagliflozin, studied in the Empagliflozin Cardiovascular CVD benefit or harm in a trial of patients recruited Outcome Event Trial in Type 2 Diabetes Mellitus Patients within 180 days of an acute coronary syndrome and (EMPA-REG OUTCOME) trial (n=7020) compared with placebo in patients with type 2 diabetes and CVD. Median followed for 25 months (ELIXA) (n=6068) NEJM follow-up 3.1 years. • Taken together, it appears that among patients with • ARR was 1.6% and the HR was 0.86 (p = 0.04 for established CVD, some GLP-1 receptor agonists may superiority) for primary composite endpoint of MACE. provide cardiovascular benefit, with the evidence of • The ARR was 2.2% and the HR was 0.62 (p < 0.001) for benefit strongest for liraglutide, favorable for cardiovascular death. semaglutide, and less certain for exenatide. There is no • The ARR was 2.6% and the HR was 0.68 (p < 0.001) for evidence of cardiovascular benefit with lixisenatide. death from any cause 13 14 Recent SGLT-2 Studies of Note Recent Studies of Note CANVAS and CANVAS-Renal Secondary Endpoint (HF) • Canagliflozin, studied in the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program (comprised of two similar trials, CANVAS and • In the EMPA-REG OUTCOME and CANVAS CVOT studies testing SGLT2 inhibitors, CANVAS-Renal); (n = 10,142) vs. placebo in participants with type 2 which enrolled participants with ASCVD, >85% of participants did not have diabetes, 66% of whom had a history of CVD. symptomatic HF at baseline. Yet, in both trials there was a clinically and statistically • Combined analysis of the two trials: Primary composite endpoint of significant reduction in hospitalization for HF for the SGLT2 inhibitor as compared MACE was reduced with canagliflozin (26.9 vs 31.5) per patient-year vs with placebo placebo; HR 0.86 (p = 0.02) for superiority in the pooled analysis, with • In the GLP-1 receptor agonist studies LEADER, SUSTAIN 6 and EXSCEL, there was no consistent findings in the component studies. significant effect on hospitalization for HF with HR 0.86 (95% CI 0.71, 1.06), 1.11 • There was a trend towards benefit for cardiovascular death, but the (95% CI 0.77, 1.61) and 0.94 (95% CI 0.78, 1.13), respectively. difference from placebo was not statistically significant in the CANVAS • Two short-term studies of liraglutide in patients with reduced ejection fraction Program. suggested a lack of benefit in this setting • Participants were followed for a median of 3.6 years 15 16 Recent DPP-4 Studies of Note Summary: Recent Studies of Note • • Among recent cardiovascular safety outcomes trials testing DPP-4 inhibitors, For the SGLT2 inhibitors studied to date, it appears that among patients with established CVD, there is likely cardiovascular benefit, with the evidence of benefit the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with modestly stronger for empagliflozin than canagliflozin. Diabetes Mellitus – Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study evaluating saxagliptin demonstrated a significant increased risk of HF, • In GLP-1 and SGLT-2 subgroup analyses of trials, lower risk individuals have not with 3.5% risk of hospitalization for HF vs 2.8% for placebo (HR 1.27; p = been observed to have an ASCVD benefit. This may be due to the short time frame of the studies and the low event rate in those without ASCVD. 0.007). • • Overall, CVOTs of dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated Subsequently, the Examination of Cardiovascular Outcomes with Alogliptin safety, i.e. non-inferiority relative to placebo, for the primary MACE endpoint, but versus Standard of Care (EXAMINE) study of alogliptin there was no not cardiovascular benefit, but possibly increasing HF risk. statistically significant difference in HF hospitalization (3.9% vs 3.3% with • There are no clinical trial data that support prescribing an SGLT2 inhibitor or GLP-1 placebo) receptor agonist with the intent of reducing cardiovascular risk in patients with an • In the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), the HbA1c <7%. rate of hospitalization for HF was 3.1% in both sitagliptin and placebo treated • Limited data suggest that there is no heterogeneity in the cardiovascular benefits patients of SGLT2 inhibitors or GLP-1 receptor agonists as a function of background glucose- lowering therapy. 17 18 3