New horizons for managing type 2 diabetes

S36

Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1–S39

Gemigliptin is a potent, selective, and long-acting DPP-4 inhibitor and also effective and well tolerated in patients with type 2 diabetes mellitus (T2DM) as either in monotherapy or in combination therapy. In addition, it is more effective in reducing glycemic variability than sitagliptin or SU as initial combination therapy with metformin in drug-naïve patients with T2DM. Various studies have shown that gemigliptin is optimized with having potent efficacy, reliable safety and compliance benefits for T2DM. In this talk, I will review the key characteristics of gemigliptin and discuss its potential benefits in the treatment of type 2 diabetes.

Lunch Seminar – Servier LN04-1 Update on existing therapy – with a focus on SUs Richard O’BRIEN1. 1University of Melbourne, Australia Metformin is recommended, in most guidelines, as first line treatment for overweight patients with type 2 diabetes. Sulphonylureas (SU) remain an initial option for non-obese patients and are useful second line therapy because they are effective and well tolerated. However, there is a common misconception that SU are inferior to modern agents such as DPP4 inhibitors in terms of complications prevention, cardiovascular (CV) risk and durability of control. Apart from metformin, SU are the only oral diabetes therapies to have shown clear reductions in microvascular complications in long term end-point trials. SGLT 2 inhibitors show promise with a recent study suggesting CV protection, but further studies are awaited. Also, these agents are not effective in patients with reduced renal function and are expensive. The effect of intensive glycaemic control with gliclazide (Diamicron MR®) was studied in the ADVANCE trial. 11,140 subjects were randomised to intensive therapy aiming for an HbA1C of <6.5%, or standard care, for 5 years. The intensive group attained an HbA1C of 6.4% vs. 7.0% in the control group. Intensive control reduced microvascular endpoints by 14% and had no adverse effect CV endpoints. These results were consistent with the effects of SU therapy seen in a previous end-point trial, the UKPDS. In that study, an HbA1C reduction of 1% resulted in a 25% reduction in microvascular endpoints over a 10 year follow up period. Gliclazide has been shown to cause less hypoglycaemia than comparable SU’s, and it is interesting to note that the rate of hypoglycaemia in ADVANCE was much lower than that of comparable studies. In the ADVANCE-ON study, 84% of the ADVANCE cohort (8,494 people) were followed for a further 5.4 years after the original trial finished. The difference in HbA1C between the intensive and control groups disappeared by the first post-trial visit, and remained similar at the end of ADVANCE-ON (intensive 7.2%, control 7.4%). End-stage renal disease resulting in death or dialysis was reduced by 64% (p = 0.007), suggesting a persisting microvascular benefit from earlier intensive glucose control with a gliclazide MR based regimen. Diabetes is a progressive process and β cell function declines gradually over time. In the UKPDS, β cell function declined at a similar rate in SU, metformin and insulin treated patients. Interest has focused on the possibility that newer diabetes drugs might preserve β cell function. The ADOPT study compared the effects of metformin, glyburide and rosiglitazone on glycaemic control over 5 years. Although rosiglitazone initially appeared to delay the progression of diabetes, by 5 years the decline in β cell function was similar in all 3 groups. Only shortterm data exists for the DPP4 inhibitors, but studies to date suggest durability of control is very similar to SU’s. There have, over many years, been concerns about the effect of SU’s on the risk of cardiovascular complications. One possible mechanism is that many of these drugs prevent the

opening of myocardial K+-ATP channels, thereby increasing the effects of ischemia on the myocardium. Gliclazide does not have this effect and, in the ADVANCE and ADVANCE-ON trials, there was no adverse effect on cardiovascular endpoints. Also, gliclazide appears to have some unique properties not shared by other SU’s. We have found that gliclazide, but not other SU’s or metformin, inhibited the oxidation of LDL and reduced markers of oxidative stress in diabetic patients. In another study, both metformin and gliclazide but not glibenclamide inhibited the progression of the intimamedia thickness of the carotid artery, an index of the progression of atherosclerosis. SU’s, and particularly gliclazide (Diamicron MR®) are effective and well tolerated agents for the treatment of type 2 diabetes and their use is well validated by large scale end-point studies. SU’s differ in their propensity to cause hypoglycaemia and in their vascular effects, and this should be taken into account when prescribing. Sulphonylureas are likely to retain a major role in diabetes treatment algorithms for the foreseeable future.

Lunch Seminar – Boehringer-Ingelheim LN09-1 New horizons for managing type 2 diabetes Hung-Yuan LI1. 1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Type 2 Diabetes Mellitus (T2DM) is a complex cardio-metabolic disorder characterized by insulin resistance, pancreatic beta cell dysfunction and hyperglycaemia. Due to the progressive nature of T2DM, maintaining glycemia as close to normal as possible can significantly reduce microvascular complications. Long-term reduction in macrovascular disease was also observed, if the glycemic control was implemented soon after diagnosis. Current treatment guidelines emphasize the importance of individualizing patient care with regard to both goals and therapies. A number of different diabetes therapies exist, allowing for personalized therapy regimens. Engage patients by involving them in healthcare decisions and selecting therapies that fit with their needs and preferences, which may enhance adherence to therapy. As the disease progresses, changes in β-cell function and insulin resistance can limit the ability of certain oral antidiabetic agents to reduce blood glucose levels. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents through insulin independent pathway that reduce hyperglycemia in patients with T2DM by reducing renal glucose reabsorption and thus increasing urinary glucose excretion (UGE). Most recent guidelines have already included SGLT2 inhibitors as one of the dual or triple therapy options, even concomitantly treatment with insulin. Drugs within the class of SGLT2 inhibitors have shown various clinical, mechanistic and theoretical effects on cardiovascular pathways and some of the cardiovascular outcome studies have been conducted to assess whether any of the individual SGLT2 inhibitor compounds has an impact on cardiovascular outcomes. Based on the placebo-controlled phase III trials in T2DM patients taking empagliflozin (one of the SGLT2 inhibitors), improved hemoglobin A1c (HbA1c) has been noted in monotherapy or add-on therapy with a low risk of hypoglycemia, reduced body weight and blood pressure, without increases in heart rate. Further investigations have also revealed the efficacy and safety data of empagliflozin in patients with certain range of impaired renal functions. In addition, empagliflozin has also been reported to reduce other CV risk markers such as visceral fat mass, uric acid, arterial stiffness and glomerular hypertension. With the positive results

Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1–S39

observed from EMPA-REG OUTCOME, more and more studies will be implemented to confirm the potential benefits and safety in patients with cardiovascular and renal disease. LN09-2 EMPA-REG OUTCOME®: Macrovascular and microvascular outcomes Ele FERRANNINI1,2. 1University of Pisa School of Medicine and CNR (National Research Council) Institute of Clinical Physiology, Pisa, Italy; 2University of Texas Health Science Center, San Antonio, Texas, USA People with type 2 diabetes (T2D) are at increased risk of vascular morbidity and mortality. Cardiovascular (CV) disease remains a major complication and is the leading cause of death associated with diabetes. While intensive glucose control reduces the risk of microvascular complications, its relationship to CV outcomes remains unclear. The management of T2D is therefore complex and necessitates treatment considerations beyond glycaemic control. In the context of these current challenges, Professor Ele Ferrannini from the University of Pisa, Italy, and the University of Texas Health Science Center in San Antonio, USA, will provide an overview of EMPA-REG OUTCOME®, the first CV outcomes trial in T2D to demonstrate improved CV outcomes in patients at high CV risk. In EMPA-REG OUTCOME®, the SGLT2 inhibitor empagliflozin was found to significantly reduce CV death compared with placebo in patients with T2D and established cardiovascular disease.1 Professor Ferrannini will begin by outlining the baseline characteristics of the trial population, background standard of care and trial endpoints. He will then explore the CV outcomes, heart failure outcomes and renal findings from the study. The trial safety findings, including those relevant to patients with renal impairment or heart failure at baseline, will also be reviewed during his presentation. Finally, Professor Ferrannini will consider the wider clinical implications of the EMPA-REG OUTCOME® trial results for future diabetes care. Reference 1. Zinman B et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117.

Lunch Seminar – Takeda LN10-1 Collaborations & combinations: Spotlight on high CV risk and T2D patients in Asia Cardiovascular outcome trials (CVOT) are increasing our understanding of how we can optimize the way we manage type 2 diabetes (T2D) patients. We want to have a conversation about what this means for endocrinologists and cardiologists treating high CV risk and hypertensive patients with T2D mellitus in Asia. This unique symposium will look at the challenges – and discuss the potential solutions – to help improve and optimize the treatment of specific patient populations in Asia. Professor Fen-Yu Tseng and Professor Bob Chilton will talk about the importance of collaboration from the perspective of endocrinologists and cardiologists – including strategies to help optimize multidisciplinary collaboration. We will spotlight the epidemiology of high CV risk and hypertensive patients, focus on CVOTs and discuss why they are important. We will present the individual trials in detail – including EXAMINE, LEADER, EMPA-REG and PROactive. We will then look at what these clinical data mean for patients and clinicians.

S37

Professor Bob Chilton and Professor Stefano Genovese will discuss the azilsartan and alogliptin treatment families. We will examine the clinical data and look at the specific patient populations for whom these treatments and treatment combinations are most appropriate. Now is the time to have a conversation about how we improve and optimize the management of high CV risk patients with T2D in Asia. Please come join us and collaborate in this symposium.

Lunch Seminar – Ascensia LN11-1 Accuracy and user performance evaluation as key factors in self-monitoring in diabetes patients Guido FRECKMANN1. 1Institute for Diabetes-Technology Research and Development Corporation, Germany For people with diabetes, self-monitoring of blood glucose (SMBG) is an essential part in the maintenance of glycemic control. Particularly for patients with intensified insulin therapy or insulin pump therapy, the availability of reliable and accurate glucose results is crucial to adequately adjust insulin doses. The international standard ISO (International Organization for Standardization) 15197 defines various requirements for SMBG systems, concerning safety and reliability, analytical performance (e.g. system accuracy), information supplied by the manufacturer and performance in the hand of lay-users. The currently applicable version of the standard is ISO 15197:2013, its predecessor was ISO 15197:2003. Regarding system accuracy, ISO 15197:2013 describes the following minimum criteria: Criterion A: At least 95% of a system’s measurement results shall fall within ±15 mg/dL of the comparison measurement results at blood glucose (BG) concentrations <100 mg/dL and within ±15% at BG concentrations ≥100 mg/dL. Criterion B: At least 99% of individual measurement results shall fall within Consensus Error Grid zones A and B. Criterion A is also applicable for user performance evaluation. A number of accuracy evaluation studies performed in recent years have reported that not all available SMBG systems show sufficient measurement quality to comply with ISO 15197 requirements. However, there are qualitative differences even among SMBG systems that comply with ISO 15197 requirements. Simulation studies show that higher accuracy leads to clinical benefit. User performance evaluation studies showed that SMBG systems showing high accuracy when used by trained professionals do not necessarily also showed high accuracy in the hands of lay-users. This underlines the importance of patient education and training, not only to avoid meter-independent factors like contamination of hands, but also to highlight meter-specific details. A reliable and accurate SMBG system is an important aspect in optimizing insulindependent patients’ therapies.

Lunch Seminar – AstraZeneca LN14-1 Is there a unifying hypothesis to explain the cardio-renal benefit of SGLT2 inhibitors? – Spotlight on the role of ketone bodies Sunder MUDALIAR1,2,3. 1University of California, 2Director Diabetes Clinic, VA San Diego Healthcare System, 3Director Special Diagnostic and Treatment Unit, VA San Diego Healthcare System, San Diego, CA, USA