LS Lunch Symposium (1-12

LS1

ADVANCES IN INSULIN AND LIPID MANAGEMENT: GLARGINE U300 AND PCSK-9 INHIBITOR INSULIN GLARGINE U300: THE NEXT GENERATION BASAL INSULIN TO REDEFINE THE LIMITS OF CONTROL

CHIA HUNG LIN

Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital

into clinical practice and it remains the most widely used. Although Gla-U100 is an effective and safe treatment, there are still many unmet needs in current clinical practice. The higher concentration of Gla-U300 has a longer duration of action than U100 and plasma insulin exposure is less variable.

The Phase III EDITION clinical trials indicated that Gla-U300 offers a similar level of glycaemic control to U100 but with a lower rate of hypoglycaemic events, in particular nocturnal episodes. Patient-level meta-analysis of EDITION 1, 2 and 3 shows the comparable glycemic control with eGFR subgroup at baseline. In a real-world assessment of patient characteristics and clinical outcomes of early users of the new insulin Gla-U300 in the US, switching to Gla-300 from other basal insulins was associated with improved glycemic control and a trend towards less hypoglycemia in patients with T2DM after 6 months.

Through the upcoming symposium, we will be sharing “real world” case studies of local Taiwan clinical experiences with the next generation insulin Gla-U300, including T2DM patients on Gla-U300 switched from OADs uncontrolled, and other basal insulin uncontrolled.

Taken together, the data suggests that Gla-U300 represents an overall better treatment option. While Gla-U300 and Gla-100 exhibit equally strong efficacy, more importantly, Gla-U300 with its

LS1

PCSK-9 INHIBITOR:OPTIMAL TREATMENT IN LIPID CONTROL

The risks of cardiovascular (CV) disease and mortality rise in association with increasing low preventive therapies, patients who have had atherosclerotic events or diabetes with risk factors remain at high risk for the occurrence of CV events. Meta-analysis combined prospective clinical studies have shown that lowers LDL-C substantially reduces the incidence of IHD and decreases major CV events incidence. International guidelines, ex. European Society of Cardiology, as well as Taiwan Lipid Guideline, hence, also recommend to treat to LDL-C level below 70mg/dL for very high CV risk patients, such as documented MI, PCI, CABG, arterial revascularization procedures…etc. and could consider to further lower LDL-C level below 55mg/dL for patients with acute coronary syndrome combining with diabetes.

Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is effective in lipid lowering and reducing cardiovascular mortality by preventing myocardial infarction and ischemic stroke. However, LDL-C goal attainment rates for CV high risk populations and patients with familial hypercholesterolemia to reach treatment targets, statin intolerance or fear of side effects caused by statin…

Alirocumab is a recently launched lipid lowering monoclonal antibody with novel mechanism, PCSK9 inhibitor. PCSK9 is an abbreviation for proprotein convertase subtilisin/kexin type 9 and mainly expressed and secreted in the liver. It plays an important role in the control of LDL-C levels by binding LDL receptor (LDLR) on the cell surface, promoting degradation of LDLR in the lysosome are proved by more than 10 large-scale international phase III trials. Regarding LDL-C lowering power on top of statins, Alirocumab delivers sustained 50-60% additional LDL-C reductions over the duration of studies. Safety profile is generally comparable to placebo and has low potential for drug interaction regardless of diabetes status. Mean HbA1c and fasting plasma glucose measurements are also comparable between Alirocumab and control groups over 52 weeks of treatment. A posthoc analysis of ODYSSEY study further showed a significant lower rate of adjudicated major CV events with Alirocumab. Based on currently available clinical evidence, Alirocumab is represent new options of lipid lowering therapy in hypercholesterolemia patients with or without atherosclerosis cardiovascular diseases to further effectively reduce recurrent ischemic events.

LS2

EXPERIENCE OF SHARED MEDICAL APPOINTMENTS IN TAIWAN

1BONIFACE J. LIN, 2PEI-FEN LEE

1.Honorary consultant, Cardinal Tien Hospital. 2.Graduate student, National Taipei University of Nursing and Health Sciences.

Shared Medical Appointment is also known as a group outpatient clinic. Dr. Joseph Pratt of the Massachusetts General Hospital in 1905 developed a group outpatient treatment for tuberculosis patients. Dr. Pratt asked the patient every day to record the weight at home and the number of hours of sleep while breathing fresh air in the backyard or balcony. Once a week in the group outpatient clinic (classroom), Dr. Pratt let the patients to compare the notes with each other, and posted the best note. Soon the patents began competing with each other and the cure rate for these poor tuberculosis patients at home became comparable with that obtained by the rich patients who lived in the expensive mountain sanatorium. In the 1920s, Dr. Pratt also used the same group method to help patients with ago, Shared Medical Appointments were gradually applied in a variety of chronic diseases such as Implementation process and method: In June 2015, we began to try this innovative model. Each time 7 to 12 patients and a few family members attended the SMA. Medical staff tried to avoid delivering lectures, mainly to let patients share the experience and ideas, learn from each other to really understand their own problems, and also enhance the ability of patients to solve the problem. In the We usually had enough time left to discuss one of the 9 items of self-management courses developed at Wilfordhall Medical Center in Texas. In our SMA, a nurse educator led the patient discussion, and a dietitian and a physician joined at any time to participate in the discussion. When the physician is not needed in the discussion, the physician is invited to examine and write prescriptions to one patient at a time at a corner of the discussion room. In order to respect the privacy of each patient, we let participated once per month increased from 26 to 89 persons. Of 68 patients who participated in more than 4 months, 87.3% of A1C attained <7%, 64.7% of BP <130/80 mmHg, 76.5% of LDL-C <100 mg / dL, and 42.6% of patients attained the goals of ABC. Eighty three % of patients agreed that SMA was helpful.

LS3

UPDATE IN GOUT MANAGEMENT: FROM VIEWPOINT OF TOTAL CARE OF METABOLIC SYNDROME

1T-Y HSIEH, 1D-Y CHEN, 2I-T LEE, 3WAYNE H-H SHEU.

1Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan, R.O.C.

Metabolic syndrome, which consists of multiple interrelated conditions, increases the risk for atherosclerotic cardiovascular disease up to 3 times and increases the risk for type 2 diabetes up to 5 times. Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. been repeatedly suggested, but no quantitative population data are available; therefore, the magnitude of the problem remains unclear. The proposed connection has been supported by the close association between hyperuricemia and insulin resistance syndrome

Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular

These findings indicate that the prevalence of metabolic syndrome is remarkably high among individuals with gout. Given the serious complications associated with metabolic syndrome, this frequent comorbidity should be recognized and taken into account in long-term treatment and overall health of individuals with gout. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases.

LS4

MOSA1C, A MULTINATIONAL OBSERVATIONAL STUDY ASSESSING INSULIN USE: UNDERSTANDING THE CHALLENGES ASSOCIATED WITH THE PROGRESSION OF THERAPY

Healthcare professionals (HCPs) and their patients consider conversations about intensifying barriers both from the HCP and the patient perspective, they needed to first be identified and then followed over years of patients’ treatment experience. That’s what inspired the MOSA1c study.

MOSAIc is a multinational, non-interventional, prospective, observational cohort study designed therapy, from both the patient’s and the physician’s perspective. Its primary objective is to determine if the characteristics of the patient, physician, and healthcare system affect progression from initial insulin therapy.

The study cohort consists of more than 4300 adults with type 2 diabetes, from 18 countries, 5 geographic regions (Asia, Europe, North America, Latin America and the Middle East) during 2-year study period. Patients on initial insulin therapy (basal insulin alone or insulin mixtures) for at least 3 months, with or without any combination of oral agents, were eligible for the study.

LS5

CLINICAL DETERMINANTS AND CHARACTERISTICS DRIVING CLINICAL DECISION IN ELDERLY T2DM MANAGEMENT

C-H CHU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Taiwan, R.O.C.

Diabetes population has increased rapidly and was estimated to reach 642 million patients in higher prevalence of type 2 diabetes (T2D) in older individuals across gender and ethnicity has also been reported. International T2D management guidelines have supported an individualized approach, considering age, body weight, comorbidities, and diabetes duration, to achieve better diabetes care. However, T2D in ageing communities associated with different underlying pathophysiology and higher risk of micro- and macro-vascular complications pose a unique challenge in clinical setting. This symposium will overview the current ageing state of T2D in Taiwan, discuss new emerging challenges, including frailty, sarcopenic obesity, and cognitive impairment, and summarize the clinical characteristics driving therapeutic decisions which should be considered. A multidimensional and multidisciplinary assessment process is essential to obtain information on medical, psychosocial, and functional capabilities, and also on how impairments of these functions could limit activities.

LS6

THE ROLE CO-MORBIDITIES PLAY IN THE CHOICE OF ANTIHYPERGLYCEMIC AGENTS FOR PATIENTS WITH TYPE 2 DIABETES

LIN, CHING-LING

Department of Metabolism & Endocrinology, Cathy General Hospital

OBJECTIVE The management of patients with type 2 diabetes has become more complex in clinicians' selection of initial therapy for most patients. However, eventually, it is conceivable that more medication will be needed in addition to metformin glycemic management with the progressive nature of type 2 diabetes. One of the challenges of T2DM management is the increasing extent of comorbidity. Most adults with diabetes have at least one morbid chronic disease, and 40% have three or more. The importance of treating patients with T2DM to target glycemic levels applies to patients with and without comorbidities in the same way. However, evidence-based diagnostic and treatment strategies should take comorbidities as treatment consideration. A position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) has suggested individualized and tailored care for T2DM, taking into account several elements, including comorbidities. The diabetes management has also moved from being “gluco-centric” to “patientcentric.” The last two decades have witnessed the development of a wide variety of new therapeutic options to treat T2DM. Although each class of these agents broadly shows similar efficacy as monotherapy with hardly any clinically meaningful differences in glucose-lowering potency at least in monotherapy most widely used in community medicine are either addition of a sulphonylurea or addition of a dipeptidylpeptidase-4 inhibitor or others. Recently, Sodium glucose transporter 2 inhibitors (SGLT2I) are also becoming one of the new second line choices after metformin. Despite raised for usage with caution, especially in patients with more comorbidity, such as elderly or CKD diabetic patients should be carefully considered. It is noteworthy that incretin-based therapies (i.e., GLP-1 receptor agonists and DPP-4 inhibitors) have become fundamental treatment options for acting in inhibition of DPP4 on the incretin system to regulate glucose homeostasis, are useful in the management of patients with T2DM over the spectrum of A1C levels, including drug-naive patients as well as those treated with other glucose-lowering therapy. Sitagliptin, one of the DPP4 inhibitors has been shown with well-tolerated in broad T2DM patient type, including renal impairment and elderly

patients. These special population patients are usually with more comorbidity to increase the challenge for the glycemic control. In addition, from recent CV safety trails data, Sitagliptin is also proven without increase CV risk in T2DM with CVD, even in the elderly or CKD patient subgroup analysis.

Since T2DM is a progressive disease, an important therapeutic issue is to ensure that each stage of treatment is as effective as possible to delay escalation of treatment intensity to the next line of treatment as long as possible. The comorbidities of T2DM patients, especially in special populations, needs to be carefully considered for their treatment options. . Maintaining a patient on an unchanged treatment is a pragmatic outcome criterion which combines notions of both effectiveness and tolerability.

LS7

THE GROWING EVIDENCE OF NEW PERSPECTIVES IN TYPE 2 DIABETES TREATMENT - SGLT2 INHIBITOR AND ITS ADDITIONAL EFFECTS

PROFESSOR WASIM HANIF MBBS, MD, FRCP

Professor of Diabetes & Endocrinology University Hospital Birmingham UK

OBJECTIVE: The prevalence of type 2 diabetes is increasing across the globe. The ADA/EASD treatment algorithm. After Metformin, nearly all the available drugs can be used depending upon the individual patients. There is a lot of emphasis on individualization of care but with no clear guidelines on how the individualization should be based. The data from a number of countries suggest that the second choice of therapy after Metformin is either Sulphonylureas or DPP-4 inhibitors. The recent trials data including the CV outcome studies suggest that perhaps the SGLT-2 inhibitors are better as second line agents. This scholastic presentation goes through the RCT evidence for the early use of SGLT-2 inhibitors in the type 2 diabetes algorithms. It also presents the latest real world data from THIN database of UK.

LS8

PATHOGENESIS AND TREATMENT IN PATIENTS WITH DIABETIC NEPHROPATHY

YASUHIKO TOMINO, MD, PHD

Professor Emeritus, Juntendo University, Tokyo, Japan Tokyo, Japan

As reported by the Japanese Society of Nephrology (JSN), 13.0 million people have chronic kidney disease (CKD). In Japan, major causes of end stage kidney disease (ESKD) are type 2 diabetic nephropathy (diabetic kidney disease), chronic glomerulonephritis, mainly IgA nephropathy, and hypertensive nephrosclerosis. I would like to focus on the pathogenesis and treatment of patients with diabetic nephropathy.

1. Pathogenesis of diabetic nephropathy

The initiation and progression factors of diabetic nephropathy have included genetic factors and/or environmental factors such as lifestyle impairment, i.e. a high protein and/or high salt diet, smoking and obesity. Advanced glycation end products (AGEs) may stimulate the growth factors as fibronectin, type IV collagen, and laminin in the glomeruli of diabetic nephropathy patients. in the progression of diabetic nephropathy. Although renal biopsy is not performed on all patients with presence of diabetic retinopathy and/or neuropathy are important findings for clinical diagnosis. In and JSD (the Japan Diabetes Society). From new biomarkers using urine and serum samples, Gohda et al. (J Am Soc Nephrol 2012; 23: 516-524 and 507-515, Curr Diab Rep 2013; 13: 560-566) reported that the concentrations of transforming necrosis factor receptors (TNFRs) strongly predict early and late renal function loss in both type 1 and 2 diabetes, independent of classical risk factors such as

2. Treatment of diabetic nephropathy

Despite the successful application of lifestyle changes, metabolic control (blood glucose: less than HbA1c of 7.0 % , LDL-C: less than 100 or 120 mg/dL), and blood pressure control (blood pressure: less than 130/80 mmHg) using ACE inhibitors and ARB, residual renal risk remains very high, leaving the diabetic population with a clear need for novel treatments. There are many therapeutic strategies to address the clinical condition, as follows: 1) adequate exercise and a low protein diet (decrease of dietary protein intake according to renal function), 2) AGE inhibitors, 3) statins, 4) eicosapentaenoic

acid (EPA), 5) renin angiotensin system blockers (ARBs), and 6) a vitamin D analogue (Kidney Blood Press Res 2014; 39: 450-489). We usually use DPP (dipeptidyl peptidase)-4 inhibitors for patients with type 2 diabetes. It is generally thought that the activated GLP (glucagon-like peptide)-1 by the sodium-glucose co-transporter 2 (SGLT2) inhibitor, i.e. a new class of diabetic medications, is used located in S1 segment of the proximal tubule in the kidneys. It is responsible for 90 % of glucose reabsorption. Inhibition of SGLT2 leads to the decrease of blood glucose levels due to the increase in renal glucose excretion. It is necessary to treat common advanced stage CKD patients, including diabetic nephropathy patients, using an oral carbonaceous adsorbent (AST-120, KremezinR) from an early stage for a long duration in order to inhibit the progression to ESKD. It consists of black spherical particles 0.2-0.4mm in diameter. Composed mainly of carbon (approximately 96%), AST-120, exhibits a superior adsorption-ability for certain acidic and basic organic compounds that are known to be increased in renal failure patients.

Although the current treatments remain suboptimal, further clinical trials are needed to identify novel therapies for patients with diabetic nephropathy.

LS9

CLINICAL APPLICATION OF GLP-1 RA ARE THERE ANY PREDICTORS OF EFFICACY FROM CLINICAL TRIALS?

Multiple new classes of diabetes treatment have emerged in the recent decade to tackle this complicated disease. This could confuse even the most experienced doctors in choosing between these new therapies. Type 2 diabetes management emphasizes the importance of individualized therapy, which should takes into account both the patient’s clinical condition and preferences. Understanding therapies affect patients.

Glucagon-like peptide-1 agonists are emerging as useful treatments since they not only lower risk of hypoglycemia.

Dulaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. Dulaglutide safety and glycemic efficacy have been previously demonstrated in the AWARD clinical trial program. based on major patient baseline characteristics in response in the sub-analysis of data from the AWARD clinical trial program. This will help physicians make informed decision when choosing different types of therapies to help patient reach their goal.

LS10

CLINICAL INTERPRETATION OF PHARMACOKINETICS AND PHARMACODYNAMICS PROFILE OF BASAL INSULIN

ANNE DORNHORST

Department of Medicine, Imperial College Healthcare NHS Trust

Glycaemic fluctuations in healthy people are tightly controlled by a number of physiological homeostatic mechanisms. For patients with type 1 and type 2 diabetes, basal insulin therapy is essential to control blood glucose level by restricting excessive hepatic glucose production in the context of insulin resistance in both the liver and the peripheral tissues, decreased insulin secretion, and excess glucagon secretion. In addition, fasting plasma glucose variability is reportedly associated with the 10-year survival of diabetes patient, with both intra-day glucose variability and HbA1c variability being independent risk factors for microangiopathy. Therefore, glucose variability may be an additional risk factor for diabetic complications, independent of hyperglycemia. Ideal basal insulin is to ensure continuous insulin coverage throughout the 24 hrs of the day with flat and predictable glucose lowering effect. As albumin binding molecules of Insulin detemir (IDet) and degludec (IDeg), and titration of treatment to achieve blood glucose control target.

LS11

NOVEL STRATEGIES FOR IMPROVING LONG-TERM OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES

S KASPERS

Boehringer Ingelheim, Corporate, Ingelheim, Germany

Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk based on the study results with intensive glycemic control. On the other hand, following a request of the US Food and Drug Administration, many large CV outcome studies have been performed in patients with longstanding disease and established CV disease to demonstrate safety of newer glucoselowering agents (saxagliptin, alogliptin, sitagliptin, lixisenatide) but did not show superiority in the CV outcomes compared with placebo.

By contrast, in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study, CV death, all-cause mortality, and hospitalization for heart failure were significantly decreased when empagliflozin was added instead of placebo to therapy for patients with high CV risk and T2DM already well treated with statins, glucose-lowering drugs, and blood pressure-lowering drugs as well as antiplatelet agents. Even though sodium–glucose cotransporter 2 inhibitors (SGLT2i) exert multiple metabolic benefits (decreases in HbA1c, body weight, and blood pressure and an increase in HDL cholesterol), all of which could reduce CVD risk, More likely, hemodynamic effects, specifically reduced blood pressure and decreased extracellular volume, are responsible for the reduction in CV mortality and heart failure hospitalization. Coincidentally, the CV outcome study with liraglutide (LEADER) also demonstrated a significant reduction of the composite endpoint (cardiovascular death, non-fatal myocardial infarction or non-fatal with established CVD.

Therefore, the latest updated guidelines in diabetic treatments recommend that adding cardiovascular and all-cause mortality.

LS12

THE ADVANCED APPLICATION OF CONTINUOUS GLUCOSE MONITORING (CGM) FROM MONITORING TO DIAGNOSIS

1CHIA-HUNG LIN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

In ‘‘professional’’ continuous glucose monitoring (CGM), the device is owned and controlled by medical professionals and patients receive no information while wearing the device. Since there are either minimal behavior changes or none at all in response to the results of professional CGM, this method is more likely to observe the patients’ actual glucose excursions. Results can be determined in between day variations in blood glucose, and the frequency of unrecognized hypoglycemia. different pattern in diabetic treatment. The mean amplitude of glucose excursion (MAGE), nocturnal high glucose, and nocturnal low glucose are highly associated with the development of diagnostic algorithms. The latest CARELINK® iPRO® PATTERN SNAPSHOT is available in the clinical practice. The combinations of currently guidelines and clinical trials, prioritizing patterns and possible causes could be listed automatically. How to use clinical judgment to determine the appropriateness of the ranked order and possible causes is a upcoming issue in the education and training of CGM.

In conclusion, professional continuous glucose monitoring can be used as not only monitoring variated therapy.