BP (1-10

BP-01

RATIONALE, DESIGN FEATURES, AND BASELINE CHARACTERISTICS: THE HEART INSTITUTE OF JAPAN-PROPER LEVEL OF LIPID LOWERING WITH PITAVASTATIN AND EZETIMIBE IN ACUTE CORONARY SYNDROME (HIJ-PROPER)

1ERISA KAWADA-WATANABE, 1HIROSHI OGAWA, 1RYO KOYANAGI, 1HIROYUKI ARASHI, 1JUNICHI YAMAGUCHI, 2KUNIHIKO MATSUI, 1NOBUHISA HAGIWARA

1Department of Cardiology, The Heart Institute of Japan, Tokyo Women’s Medical University, Tokyo, Japan 2Department of General and Community Medicine, Kumamoto University Hospital, Kumamoto, Japan

BACKGROUND: In contrast to current guidelines in Western countries, moderate reduction of low-density lipoprotein cholesterol (LDL-C) is recommended for Japanese patients with atherosclerotic cardiovascular disease and dyslipidemia even in secondary prevention. HIJ-PROPER (Heart Institute of Japan-PRoper level of lipid lOwering with Pitavastatin and Ezetimibe in acute coRonary syndrome) is a prospective, randomized, open-label, blinded endpoint multicenter trial designed to assess whether closely controlled LDL-C lowering with a standard statin dose plus ezetimibe, targeting LDL-C of < 70mg/dL, would reduce cardiovascular events more than standard statin monotherapy targeting LDL-C of < 100mg/dL as per the Japan Atherosclerotic Society guideline in patients with acute coronary syndrome (ACS) and dyslipidemia.

METHODS: We recruited patients with ACS and dyslipidemia who had undergone coronary angiography. Participants are randomly allocated to either intensive LDL-C lowering treatment (target LDL-C of < 70mg/dL; pitavastatin plus ezetimibe) or standard LDL-C lowering treatment (target LDL-C of 90-100mg/dL; pitavastatin monotherapy). The primary endpoint is a composite of total death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, and any ischemia-driven revascularization. Patients will be followed for a minimum of 3 years.

RESULTS: Between January 2010 and April 2013, 1734 patients were enrolled from 19 hospitals in Japan with a mean age of 65.6 years; 75.5% were men and 83.3% were statin-naïve. The qualifying

CONCLUSION: HIJ-PROPER will determine whether targeting LDL-C of < 70mg/dL with pitavastatin plus ezetimibe can improve cardiovascular outcomes in Japanese patients with ACS and dyslipidemia in comparison to targeting LDL-C of 90-100mg/dL with standard pitavastatin monotherapy.

BP-02

HAEMODYNAMIC EFFECTS OF COMBINATION THERAPY WITH THE DPP-4 INHIBITOR LINAGLIPTIN AND RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN PATIENTS WITH TYPE 2 DIABETES

1M E COOPER, 2V PERKOVIC, 1,3P-H GROOP, 4B HOCHER, 5J CESCUTTI, 6T MEINICKE, 6A KOITKA-WEBER, 7S THIEMANN, 7M EYNATTEN

1Baker IDI Heart and Diabetes Institute, Melbourne, Australia 2George Institute for Global Health, Sydney, Australia 3Division of Nephrology, Department of Medicine, Helsinki, Finland 4Institute of Nutritional Science, University of Potsdam, Potsdam, Germany 5Boehringer Ingelheim, Reims, France 6Boehringer Ingelheim, Biberach, Germany 7Boehringer Ingelheim, Ingelheim, Germany

Background and aims: People with type 2 diabetes often require multi-drug therapy for adequate vascular risk factor management. Previous mechanistic clinical studies hypothesised an unfavourable potential drug-drug interaction between dipeptidyl peptidase (DPP)-4 inhibitors and angiotensin-converting enzyme inhibitors (ACEi) by postulating a clinically relevant increase in sympathetic activity and rise in blood pressure. We therefore investigated whether initiation of the DPP-4 inhibitor linagliptin on a background of renin-angiotensin system (RAS) blockade may alter clinical haemodynamic conditions.

Materials and methods: MARLINA–T2D™, a multicentre, double-blind, placebo-controlled clinical trial, randomised 360 patients with type 2 diabetes on a stable background of single RAS blockade (ACEi 33.3% [n = 120]; angiotensin receptor blocker [ARB] 66.7% [n = 240]) to either linagliptin (n = 182) or placebo (n = 178). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was considered as an exploratory safety endpoint and was conducted at baseline (BL) and after 24 weeks of treatment.

Results: In the treated set population, ABPM data were available for 298 patients (linagliptin, n = 155; placebo, n = 143) at baseline. Overall mean (SE) BL 24-h systolic blood pressure (SBP), diastolic BP (DBP), and pulse rate were 132.7 (0.7) mmHg, 75.9 (0.5) mmHg, and 77.3 (0.6) bpm, respectively. At week 24, treatment with linagliptin was not associated with any clinically relevant haemodynamic changes: placebo-adjusted mean (SE) 24-h SBP, DBP, and pulse rate changes from BL were 0.0 (1.4) mmHg (95% CI –2.7, 2.7; NS), 0.0 (0.8) mmHg (95% CI –1.5, 1.5; NS), and 0.8 (0.7) bpm (95% CI –0.7, 2.2; NS), respectively. The presence of either ACEi or ARB background therapy at BL provided similar results (Table).

Conclusion: Adding linagliptin to stable RAS blockade background therapy was not associated with systemic haemodynamic changes. Our study supports its concomitant use for dual enzyme blockade of DPP-4 and ACE in patients with type 2 diabetes.

BP-03

EFFECT OF EMPAGLIFLOZIN ON ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES AND HIGH CARDIOVASCULAR RISK

1C WANNER, 2B ZINMAN, 3S E INZUCCHI, 4M MATTHEUS, 4A KOITKA-WEBER, 4M EYNATTEN, 5H J L HEERSPINK, 6D CHERNEY.

1Dept of Medicine, Würzburg Univ Clinic, Würzburg, Germany 2Lunenfeld-Tanenbaum Research Inst, Mount Sinai Hospital, Toronto, Canada 3Section of Endocrinology, Yale Univ, New Haven, CT 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 5Dept of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands 6Toronto General Hospital, Univ of Toronto, Canada.

Background: with type 2 diabetes (T2D). The present analysis aimed to explore short- and long-term effects of EMPA on albuminuria in EMPA-REG OUTCOME®.

Methods: Patients with T2D and established cardiovascular (CV) disease were randomized (1:1:1) to EMPA 10 mg, 25 mg or placebo in addition to standard of care. Changes in urinary albuminto-creatinine ratio (UACR, log-transformed) from baseline were analyzed for EMPA pooled vs placebo using a mixed model repeated measures analysis.

Results: 7020 patients were treated. At baseline, 59%, 29% and 11% had normo-, micro- and macroalbuminuria, respectively. At Week 12, placebo-corrected adjusted geometric mean ratio of UACR change from baseline with EMPA pooled was -7% (95%CI -12, -2; p = 0.0132), 25% (95%CI -31, -19; p < 0.0001) and -32% (95%CI -41, -23; p < 0.0001) in patients with normo-, micro- or macroalbuminuria at baseline, respectively. At Week 164, placebo-corrected adjusted geometric mean ratio of UACR change from baseline with EMPA pooled was -12% (95%CI -21, -4; p = 0.0072), -30% (95%CI -39, -19; p < 0.0001) and -32% (95%CI -47, -13; p = 0.0020) in these subgroups, respectively (Figure).

Conclusions: In patients with T2D and established CV disease, EMPA led to significant reductions in UACR from as early as Week 12, regardless of baseline albuminuria status. These results support both short- and long-term renal effects of EMPA on UACR.

BP-04

RAPID ONSET OF RENAL EFFECTS WITH EMPAGLIFLOZIN IN TYPE 2 DIABETES: A CUMULATIVE RENAL EVENT ANALYSIS OVER TIME IN THE EMPA-REG OUTCOME® TRIAL

1C WANNER, 2A KOITKA-WEBER, 2M MATTHEUS, 2M EYNATTEN, 3M E COOPER

1Dept of Medicine, Würzburg Univ Clinic, Würzburg, Germany 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 3Baker IDI Heart and Diabetes Institute, Melbourne, Australia.

Background: Patients with diabetes are at high risk of developing chronic kidney disease in patients with type 2 diabetes and established cardiovascular disease. To further explore the onset of the observed renal effects with EMPA we investigated hazard ratios (HRs) over time for the composite outcome of incident or worsening nephropathy.

Methods: Patients were randomized to receive EMPA 10mg, 25mg or placebo in addition to standard of care. The cumulative probabilities of experiencing incident or worsening nephropathy (i.e. progression to macroalbuminuria, doubling of serum creatinine accompanied by eGFR [MDRD] 2, initiation of renal replacement therapy or death due to renal disease) were CIs (obtained from Cox regression analyses) were derived at each time point following randomization until the last observation of the last patient. All events until the respective cut-off day were considered and patients without events were censored at that day.

Results: stabilized as the number of patients with events increased over time.

Conclusions:

BP-05

HEART FAILURE HOSPITALISATION OR CARDIOVASCULAR DEATH WITH EMPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES AND HIGH CARDIOVASCULAR RISK: ANALYSIS OVER TIME

1D FITCHETT, 2J GEORGE, 2J LEE, 2H-J WOERLE

1St Michael's Hospital,Division of Cardiology, University of Toronto, Toronto, Canada 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Background and aims: In the EMPA-REG OUTCOME trial, empagliflozin (EMPA) given in (3-point MACE; composite of CV death, non-fatal myocardial infarction, non-fatal stroke) in patients with type 2 diabetes (T2DM) and high CV risk. This reduction was driven by a 38% reduction in CV death vs placebo (PBO). EMPA also reduced hospitalisation for heart failure by 35% and the composite of heart failure hospitalisation or CV death by 34%. We investigated hazard ratios with EMPA vs PBO for the composite of heart failure hospitalisation or CV death at time points following randomisation.

Materials and methods: Patients were randomised to receive EMPA 10 mg, EMPA 25 mg, or PBO in addition to standard of care. The cumulative probabilities of experiencing the composite of heart failure hospitalisation or CV death were analysed for pooled EMPA versus PBO in patients ratios and 95% confidence intervals (obtained from Cox regression analyses) were derived at each time point following randomisation until the last observation of the last patient. All events until the respective day were considered and patients without events were censored at the respective day.

Results: Reductions in the risk of heart failure hospitalisation or CV death with EMPA vs PBO were observed by the first month and persisted for the duration of the trial (Figure). Hazard ratio stabilised as the number of patients with events increased over time.

Conclusion: In patients with T2DM and high CV risk, an early reduction in the risk of heart failure hospitalisation or CV death was observed in patients treated with EMPA. This reduction in risk persisted throughout the duration of the trial.

BP-06

FACTORS ASSOCIATED WITH INSULIN ADHERANCE AMONG PATIENTS WITH TYPE 2 DIABETES: THE MOSAIC STUDY

1THOMAS LEW (PRESENTER ONLY),

2MENGDONG HE, 3BRADLEY H. CURTIS, 3JAY BAE, 3AYAD K. ALI, 4WILLIAM H. POLONSKY, 5LUCAS RISTA, 6SALEM A. BESHYAH, 7MARTHA M. FUNNELL, 8RENAN MAGALHAES MONTENEGRO JR, 8VIRGINIA FERNANDES, 2SEOYOUNG C. KIM

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Brigham and Womens Hospital, Boston, MA, USA; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Diabetes Behavioral Institute, Del Mar, CA, USA; 5University Rosario, Rosario, Argentina; 6Diabetes Clinic, Abu Dhabi, United Arab Emirates; 7University of Michigan, Ann Arbor, MI, USA; 8Universidade Federal do Ceará (UFC), Fortaleza-Ceara, Brazil

While insulin is the most effective glucose lowering therapy, adherence varies widely. Few studies insulin nonadherence within MOSAIc, a 2-year prospective cohort study. Patients with type 2 diabetes clinical, and self-reported data were collected at baseline and over 2 years. Insulin nonadherence was regression and multiple imputations were used in the analyses. Among 2706 patients, mean (standard deviation) age was 62.1 (10.8) years, 50% were female, and 608 (29.3%) were nonadherent at the end of study. These patients were younger (p < .0001), had lower diabetes knowledge test scores (p = .04), and were likely to be nonadherent at baseline (p < .0001), use mixed insulin (p = .0003), inject > 1 time per day (p = .001), have a worse experience with their insulin delivery system (p = .01), and have poor communication with their physicians compared to adherent patients. After adjustment, age and our study indicates that among patients with T2D utilizing insulin, younger patients with a history of poor adherence are less likely to be adherent over time.

Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at the American Diabetes Association –

BP-07

DEMOGRAPHIC AND CLINICAL FACTORS MAY PREDICT INSULIN PROGRESSION AND GLYCEMIC CONTROL AMONG PATIENTS WITH TYPE 2 DIABETES USING INSULIN: LEARNING FROM THE MOSAIC STUDY

1THOMAS LEW (PRESENTER ONLY),

2AYAD K. ALI, 2BRADLEY H. CURTIS, 3JAMES R. ROGERS, 3MENGDONG HE, 3ABDURRAHMAN ABDURROB, 4BRUNO LINETZKY, 2JAY BAE, 2RAN DUAN, 5STEVE BAIN, 6MANOJ CHAWLA, 7YOEL TOLEDANO, 8IKURO MATSUBA, 9MUSTAFA ARAZ, 10WILLIAM H. POLONSKY, 3SEOYOUNG C. KIM

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA; 4Eli Lilly and Company, Buenos Aires, Argentina; 5Swansea University, Swansea, UK; 6Lina Diabetes Care Centre, Mumbai, India; 7Hillel Yaffe Medical Center, Maccabi, Petah Tikva, Israel; 8Kanagawa Physicians Association, Kanagawa, Japan; 9Gaziantep University, Gaziantep, Turkey; 10Diabetes Behavioral Institute, Del Mar, CA, USA

MOSAIc is a multinational 2-year prospective cohort study designed to understand challenges associated with insulin progression in patients with type 2 diabetes (T2D). This analysis describes characteristics of patients who had insulin progression over the 2-year period according to their 3 months with/without other antidiabetes medications seen as part of their usual care, in 18 countries. Data were measured during patient visits to physicians, semiannually for 2 years. Insulin progression the study period, a total of 924 patients had insulin progression. Of those, only 28% achieved glycemic control at Year 2. Those who achieved glycemic control were older, with lower baseline HbA1c; majorities were males, nonsmokers, and those with a family history of diabetes. In addition, 30% of this group still had their HbA1c level above their physician’s stated treatment goal. In conclusion, there are important demographic and clinical differences at baseline among patients with T2D with insulin progression by glycemic control status.

Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at the American Diabetes Association –

BP-08

EFFICACY AND SAFETY BY BASELINE A1C WITH ONCE-WEEKLY DULAGLUTIDE IN THE AWARD PROGRAM

1THOMAS LEW (PRESENTER ONLY),

2SAMUEL DAGOGO-JACK, 3VIVIAN THIEU, 4MARIA YU, 3NAN ZHANG, 3DARA SCHUSTER, 3LUIS-EMILIO GARCIA-PEREZ

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2University of Tennessee Health Science Center, Memphis, TN, USA; 3Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN, USA; 4Eli Lilly Canada, Danforth, Canada

Dulaglutide (DU), a once-weekly glucagon-like peptide-1 receptor agonist, was studied in the AWARD clinical trial program in adult patients with type 2 diabetes (T2D) and demonstrated

To evaluate the efficacy and safety of DU 1.5 mg and DU 0.75 mg in patients with T2D by months.

Across 7 studies, 55% to 82% of the DU-treated patients had a baseline A1c < 8.5%, and 18% 8.5%, respectively, were: DU 1.5 mg: -0.67% to -1.25% and -1.22% to -2.37%; DU 0.75 mg: -0.53% to -1.07% and -1.37% to -2.19%. The A1c reduction from the pooled analysis was greater in patients and -1.02%; DU 0.75 mg: -1.75% and -0.83%. DU treatments were well tolerated among baseline A1c subgroups.

Across the AWARD program, DU 1.5 mg and DU 0.75 mg demonstrated significant A1c

Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at American Diabetes Association – 76th

BP-09

EFFICACY AND SAFETY BY DURATION OF DIABETES WITH ONCEWEEKLY DULAGLUTIDE IN THE AWARD PROGRAM

1THOMAS LEW (PRESENTER ONLY),

2BAPTIST GALLWITZ, 3IMRE PAVO, 4VIVIAN THIEU, 4NAN JIA, 4NAN ZHANG, 4LUIS-EMILIO GARCIA-PEREZ

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2University of Tübingen, Tübingen, Germany; 3Eli Lilly Regional Operations, Vienna, Austria; 4Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN, USA

Dulaglutide (DU), a once-weekly glucagon-like peptide-1 receptor agonist, was studied in the AWARD clinical trial program in adult patients with type 2 diabetes (T2D) and demonstrated

To evaluate the efficacy and safety of DU 1.5 mg and DU 0.75 mg in patients with T2D by analysis on the completed studies, AWARD-1, -2, -5, -6, and -8, at 6 months. AWARD-3 and -4 were not included in the analysis because, due to the population studied, small numbers of patients had DoD

Across the 5 studies, the proportions of patients with DU treatment were similar among DoD respectively, were: DU 1.5 mg: -1.19% to -1.54%, -1.16% to -1.56%, and -1.04% to -1.50%; DU 0.75 mg: -0.90% to -1.28%, -0.94% to -1.21%, and -0.82% to -1.38%. The A1c changes were similar from -1.27%, and -1.17%; DU 0.75 mg: -1.02%, -0.93%, and -0.98%, respectively. The effects on weight were similar among DoD subgroups with both DU doses, respectively. DU treatments were well tolerated among DoD subgroups.

In conclusion, irrespective of DoD, patients treated with DU demonstrate similar A1c reduction,

Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at the American Diabetes Association –

BP-10

ASSESSING THE ECONOMIC BURDEN OF PATIENTS WITH HYPOGLYCEMIA IN TAIWAN USING THE NATIONAL HEALTH INSURANCE RESEARCH DATABASE (NHIRD)

1CJ CHANG, 2,3HSIEH AN-TSZ, 5THOMAS LEW, 4BRUCE C.M. WANG, 4WESLEY FURNBACK; 6WEE TECK NG, 6ALENA STRIZEK

1Medical Statistics Research Center, Chang Gung University, 2Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan, 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, 4Elysia Group Ltd., Taipei, Taiwan, 5Eli Lilly and Company (Taiwan), Inc., 6Eli Lilly and Company, Indianapolis, IN, USA

Purpose: For patients with type 2 diabetes mellitus (T2DM), hypoglycemia, whether severe economic burden of the disease. This study aims to quantify the economic burden of hypoglycemia in Taiwan using the National Health Insurance research database (NHIRD), a claims-based dataset encompassing 99% of Taiwan’s population.

Methods: Using the NHIRD 2 million patient sample, the index period ran from 2001 to 2012 with 2000 and 2013 serving as the pre- and post-index periods, respectively. Patients were indexed into the study if they had a diagnosis of T2DM during the index period, had a minimum of 12 months continuous enrollment in their pre- and post-index periods, and did not meet any exclusion criteria. Patients with a hypoglycemic episode (HE) (defined by ICD-9 code) during the index period were A matched study cohort of patients with T2DM which did not have a HE was also identified and matched 4:1 on index date, age, sex, and the Charlson Comorbidity Index (CCI) to the HE cohort for comparison.

Results: direct medical costs for patients with and without incident HEs were NT$173,701 and NT$93,275, respectively. The incremental mean annual direct costs between the HE cohort and without HE cohort was NT$80,426. Incremental costs between the HE and non-HE cohorts were driven by higher mean annual inpatient costs (NT$42,654), outpatient costs (NT$31,718), and emergency department costs (NT$6,055).

Conclusion: The economic burden of Taiwanese T2DM patients with HEs is substantially higher than T2DM patients not experiencing HEs. The introduction of new diabetic therapies with improved improving the health outcomes of Taiwanese patients.