BP：廠商論文壁報展示 (1-6

BP-1 EFFICACY OF INVESTIGATIONAL DULAGLUTIDE DOSES OVERALL AND BY BASELINE HBA1C AND BMI: EXPLORATORY SUBGROUP ANALYSIS OF THE AWARD-11 TRIAL

1ENZO BONORA, 2JUAN FRIAS,

3LUIS NEVAREZ RUIZ, 4ZHUOXIN YU,

4ZVONKO MILICEVIC,

4RALEIGH MALIK,

4ANGELYN BETHEL,

4DAVID COX,

5THOMAS LEW (NON-AUTHOR PRESENTER)

1University of Verona, Verona, Italy; 2National Research Institute, California, USA; 3Hospital Angeles Chihuahua, Chihuahua, Mexico; 4Eli Lilly and Company, Indianapolis, Indiana, USA;

5Eli Lilly and Company, Taipei,

Taiwan, R.O.C

Background and aims: Dulaglutide (DU) is approved at doses of 0.75 and 1.5 mg for type 2 diabetes (T2D). The AWARD-11 trial assessed whether higher DU doses (3 mg and 4.5 mg) provide further improvements over the 1.5 mg dose in glucose and body weight (BW) in patients with T2D inadequately controlled with metformin monotherapy. Exploratory prespecified subgroup analyses assessed the effect of DU on HbA1c and BW reduction by baseline HbA1c (< 8.5% or ≥ 8.5%) and BMI (< or ≥ median [34.2 kg/m2]).

Materials and methods: Patients were randomized (1:1:1) to once-weekly DU 1.5 mg (n = 612), DU 3 mg (n = 616), and DU 4.5 mg (n = 614). All patients initiated once-weekly DU 0.75 mg for 4 weeks, followed by step-wise dose escalation every 4 wks to the randomized dose. The primary objective was change in HbA1c from baseline at 36 wks. Secondary objectives included change in BW and % of pts achieving HbA1c < 7% at 36 wks.

Results: At baseline patients had a mean age of 57.1 yrs, HbA1c of 8.6%, and BW of 95.7 kg. At the 36-wk primary endpoint, both the DU 3 mg and 4.5 mg doses were superior to the DU 1.5 mg dose for HbA1c change (1.5 mg, -1.5%; 3 mg, -1.7% [p = 0.003]; 4.5 mg, -1.9% [p < 0.001]), % of patients achieving HbA1c < 7% (1.5 mg, 57%; 3.0 mg, 65% [p = 0.006]; 4.5 mg, 71% [p < 0.001]) and BW (1.5 mg, -3.1 kg; 3 mg, -4.0 kg [p = 0.001]; 4.5 mg, -4.7 kg [p < 0.001]). Treatment group differences in HbA1c change favored the higher doses vs the 1.5-mg dose in each HbA1c subgroup, with dose-related HbA1c improvements being larger in the higher baseline HbA1c subgroup. BW reduction was dose related in each baseline HbA1c subgroup but was larger among patients with lower baseline HbA1c. Treatment effects on HbA1c were similar between baseline BMI subgroups. Absolute BW reduction was larger across dose groups in the higher baseline BMI subgroup, but treatment group differences were similar between subgroups. Common adverse events were similar between HbA1c and BMI subgroups.

Conclusions: In patients with T2D and inadequate glycemic control on metformin, escalation from DU 1.5 mg to DU 3 mg or DU 4.5 mg once-weekly provided clinically relevant, dose-related

improvements in HbA1c and BW overall and in subgroups of baseline HbA1c and BMI. Consistent with results from other GLP-1 agonists, dose-related improvements in HbA1c were larger among patients with higher baseline HbA1c, whereas dose-related BW reduction was larger among patients with lower baseline HbA1c.

BP-2 PREFERENCES AND HEALTH STATE UTILITIES ASSOCIATED WITH ROUTES OF ADMINISTRATION FOR ORAL SEMAGLUTIDE, INJECTABLE SEMAGLUTIDE AND DULAGLUTIDE

1KRISTINA BOYE, 2KATELYN CUTTS, 2KATIE STEWART, 3KIRSI NORRBACKA,

4LUIS-EMILIO GARCÍA-PÉREZ,

2LOUIS MATZA, 5THOMAS LEW (NON-AUTHOR

PRESENTER)

1

Eli Lilly and Company, Indianapolis, IN, USA; 2Patient-Centered Research, Evidera, Bethesda, MD, USA; 3Eli Lilly Finland, Helsinki, Finland; 4Lilly S.A., Alcobendas, Spain;

5Eli Lilly and Company, Taipei, Taiwan, R.O.C

OBJECTIVE: Previous studies have examined health state utilities (which are preference weightings for use in cost-effectiveness analyses) associated with injectable GLP-1 receptor agonists for treatment of type 2 diabetes (T2D). An oral formulation of semaglutide (sema) has recently become available. This study estimates health state utilities representing preferences associated with routes of administration for daily oral sema and two weekly injectable GLP-1 receptor agonists.

METHODS: Participants with T2D in the UK valued four health state vignettes (drafted based on drug labels and device instructions for use) in time trade-off interviews to estimate preference-based utility scores. The vignettes had identical descriptions of T2D, but differed in treatment process: (1) daily simple oral treatment (tablets without specific administration requirements), (2) daily oral sema (tablet with administration requirements per product label), (3) weekly dulaglutide (dula) injection, (4) weekly sema injection.

RESULTS: Interviews were completed by 201 participants (52.7% male; mean age = 58.7). Preferences among routes of administration varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral sema, 0.878 for dula injection, and 0.859 for sema injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences among the four utility scores (p < 0.01), except the comparison between oral sema and dula which was not significant (p = 0.49).

CONCLUSIONS: While some participants preferred daily oral treatment, others preferred one of the weekly injections. Results suggest that patient preferences for routes of administration cannot be compared using only the simplest descriptions (e.g., “oral” vs. “injectable”). The details of treatment administration and treatment frequency have an impact on preference and should be considered.

BP-3 CONVERSATIONS AND REACTIONS AROUND SEVERE HYPOGLYCEMIA (CRASH): SURVEY RESPONSE OF PEOPLE AGED 65+ WITH TYPE 1 DIABETES OR INSULIN-TREATED TYPE 2 DIABETES AND CAREGIVER

1FRANK SNOEK, 2ERIK SPAEPEN, 3DONALD M BUSHNELL, 2CHRISTOPHER J CHILD,

3ZANETA BALANTAC, 2BETH D MITCHELL, 4MARK PEYROT, 5THOMAS LEW (NON-

AUTHOR PRESENTER)

1Amsterdam University Medical Centers, Amsterdam, The Netherlands, 2Eli Lilly and Company, Indianapolis, United States, 3Evidera, Bethesda, United States, 4Loyola University, Baltimore, United States, 5Eli Lilly and

Company, Taiwan, R.O.C

Background and aims: The CRASH online survey examined the experience and treatment of a severe hypoglycemic event (SHE) in people with type 1 diabetes (T1DM) or insulin-treated type 2 diabetes (T2DM) or their caregivers (CGs).

Materials and methods: Eligible participants experienced ≥ 1 SHE in the last 3 years with insulin treatment at the time of event. Reported here are results from people with diabetes (PWD) aged ≥ 65 years and CGs of PWD ≥ 65 years old from Canada, Germany, Spain, UK, and USA.

Results: Because the majority of the responses were similar between T1D PWD (N = 74) and CGs (N = 95) and also between T2D PWD (N = 104) and CGs (N = 231), results were combined for PWD and CGs and are reported as ‘T1DM’ (PWD and CGs) and ‘T2DM’ (PWD and CGs), respectively. During the last SHE, reported glucagon use was low for T1DM (9.5%) and T2DM (7.5%); primary reason reported was no prescription available or filled (T1DM 24.3%, T2DM 29.3%). Of those who ever discussed SHE at their healthcare provider (HCP) visit (T1DM 138, T2DM 243), less than half (T1DM 41.3%, T2DM 34.2%) reported discussion of SHE at every HCP visit. No discussion of the most recent SHE occurred for 34.3% (T1DM) and 31.0% (T2DM). During the most recent SHE many felt unprepared (T1DM 35.5%, T2DM 47.2%), scared (T1DM 60.9%, T2DM 64.2%), and helpless (T1DM 39.1%, T2DM 51.3%). After the last SHE, changes were reported to insulin regimens, meal plans, carrying sugar/sweets, checking blood glucose more often or using continuous glucose monitors, and increasing access to glucagon.

Conclusions: Clinical guidelines recommending discussion of hypoglycemia at each HCP visit for PWD at risk for SHE are not being met and should occur, and CGs should be included in preparedness strategies.

BP-4 EFFECT OF DULAGLUTIDE OF KIDNEY FUNCTION-RELATED OUTCOME IN TYPE 2 DIABETES: POST HOC ANALYSIS FROM REWIND TRIAL

1JONATHAN SHAW, 2FADY T. BOTROS,

2RALEIGH ELIZABETH MALIK, 2CHARLES

MESSAN ATISSO, 3HELEN COLHOUN,

4HERTZEL GERSTEIN, 5THOMAS LEW (NON-

AUTHOR PRESENTER)

1Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; 2Eli Lilly and Company, Indianapolis, IN, USA; 3University of Edinburgh, Edinburgh, Scotland, UK; 4Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada; 5Eli Lilly and Company, Taipei, Taiwan, R.O.C

Background and Aims: In participants with type 2 diabetes (T2D) in the REWIND trial, dulaglutide (DU) use for a median follow-up of 5.4 years was associated with a reduction in the composite renal outcome, defined as first occurrence of new macroalbuminuria, sustained decline in estimated glomerular filtration rate (eGFR) of ≥ 30%, or chronic renal replacement therapy.

Objective: To evaluate the effect of dulaglutide on renal outcomes related to kidney function that are typically used in renal outcomes studies, defined as the composite endpoint of sustained eGFR decline ≥ 40%, end-stage renal disease (ESRD), or all-cause death.

Materials and Methods: Participants with T2D and cardiovascular (CV) disease or CV risk factors were randomized (1:1) to DU 1.5 mg once-weekly or placebo. This post hoc analysis used Cox proportional hazards modeling for time-to-first-event to determine the risk of renal outcomes. Two additional sensitivity analyses were conducted by replacing the “all-cause death” component initially with “CV or renal death” component, or “renal death only” component.

Results: At baseline, treatment groups had similar eGFR (mean ± SD: DU = 77.2 ± 22.7; placebo = 76.6 ± 22.8). The incidence rate of the composite endpoints was significantly lower for the DU group compared with placebo with 17% risk reduction when including all-cause death, 18% risk reduction when including CV or renal death, and 28% risk reduction when only including renal death This effect was mainly driven by the significantly lower proportion of participants with sustained eGFR decline ≥ 40% in the dulaglutide group compared to placebo.

Conclusion: Treatment with DU 1.5 mg was associated with a 17% risk reduction in kidney function-related outcomes, suggesting potential delay in progression of diabetic kidney disease in patients with T2D and established CV and CV risk factors.

BP-5 EMPAGLIFLOZIN FACILITATES SUSTAINED INSULIN DOSE REDUCTIONS IN PATIENTS WITH TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE: THE EMPA-REG OUTCOME TRIAL

1M VADUGANATHAN, 2N SATTAR, 3D FITCHETT, 4AP OFSTAD, 5,6M BRUECKMANN,

5J GEORGE,

3S VERMA, 7M MATTHEUS, 8C WANNER, 9SE INZUCCHI, 10B ZINMAN,

11J BUTLER

1Brigham and Women’s Hospital, Harvard Medical School, Boston, USA; 2University of Glasgow, Glasgow,

United Kingdom; 3

St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; 4Boehringer Ingelheim KS, Asker, Norway; 5Boehringer Ingelheim International Pharma GmbH, Ingelheim, Germany;

6

University of Heidelberg, Mannheim, Germany; 7Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; University Hospital Würzburg, Würzburg, Germany; 8 9Yale University School of Medicine, YaleNew Haven Hospital, New Haven, CT, USA; 10Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; 11University of Mississippi, Jackson, MS, USA

Background: Many patients with T2D require insulin therapy and reducing insulin requirements is attractive to both patients and practitioners. Limited data are available regarding the effects of SGLT-2 inhibitor initiation on background insulin doses.

Methods: In EMPA-REG OUTCOME, 7,020 patients were treated with empagliflozin (EMPA) 10, 25mg, or placebo (PBO). This analysis focuses on the 3,387 (48%) patients treated with insulin at baseline. After the first 12 weeks, changes in background antihyperglycemic therapy were permitted. We assessed treatment effects of pooled EMPA arms vs. PBO on time to sustained total daily insulin dose reduction from baseline by 10%, 20%, and 30% for at least 2 consecutive study visits by Cox regression adjusting for baseline risk factors. Dose reductions were considered appropriate if they were accompanied by no subsequent change (defined as < 0.2% increase) or a decrease in subsequent HbA1c.

Results: EMPA significantly increased the proportion of patients achieving sustained and appropriate (without increases in HbA1c) insulin dose reductions by > 20% from baseline compared with PBO after accounting for key covariates (adj. HR 1.87 [95% CI: 1.39-2.51]; P < 0.0001). Similarly, consistent benefits were observed when considering sustained insulin dose reductions of > 10% from baseline in EMPA vs. PBO (14.0% vs. 7.5%; adj. HR 1.91 [95% CI: 1.50-2.43]; P < 0.0001) or > 30% from baseline (5.6% vs. 3.3%; adj. HR 1.68 [95% CI: 1.17-2.43]; P = 0.0055).

Conclusions: Among insulin-treated patients with T2D and CVD, EMPA facilitates meaningful, sustained, and appropriate reductions in insulin requirements.

BP-6 EFFECT OF EMPAGLIFLOZIN ON CARDIORENAL OUTCOMES AND MORTALITY ACROSS BMI CATEGORIES: SUBGROUP ANALYSIS OF THE EMPA-REG OUTCOME TRIAL WITH A FOCUS ON ASIAN PATIENTS

1Q JI,

2L JI, 3Y MU, 4J ZHAO, 5B ZINMAN, 6C WANNER, 7JT GEORGE, 8I ZWIENER,

9K UEKI, 10K YOKOTE, 11W OGAWA, 12OE JOHANSEN

1

Department of Endocrinology, Shaanxi Aerospace Hospital, Xi'an, China; 2Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China; 3Department of Endocrinology, Chinese PLA General Hospital, Beijing, China; 4Shandong Provincial Hospital, Shandong University, Jinan, China; 5LunenfeldTanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 6Department of Medicine, Wuerzburg University Clinic, Wuerzburg, Germany; 7Boehringer Ingelheim International GmbH, Ingelheim, Germany; 8Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; 9Department of Molecular Diabetic Medicine, Diabetes Research Center, National Center for Global Health and Medicine, Tokyo, Japan; 10Department of Endocrinology, Hematology, and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan; 11Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; 12Boehringer Ingelheim Norway KS, Asker, Norway

Background and aims: Epidemiology studies show a J- or U-shaped relationship between body-mass index (BMI) and mortality where individuals at the lower end of the BMI distribution, as well as those who are overweight/obese, have increased risk of mortality. Although obesity characteristics differ between Caucasian and Asian populations, such a relationship is observed in both populations. We explored the association between differing BMI at baseline, according to World Health Organization categories (< 25, 25 to < 30, ≥ 30 kg/m2), and mortality and cardiorenal outcomes with empagliflozin (EMPA), a sodium-glucose co-transporter-2 inhibitor, in the EMPAREG OUTCOME trial.

Materials and methods: In EMPA-REG OUTCOME, patients with type 2 diabetes (T2D) and prior cardiovascular (CV) disease were treated with EMPA or placebo (PBO) (median followup: 3.1 years). We used Cox regression to analyse post hoc the effects of EMPA vs PBO on all-cause mortality, the composite of CV death (excluding fatal stroke) or hospitalisation for heart failure (HHF), and incident or worsening nephropathy across baseline BMI categories (< 25, 25 to < 30, ≥ 30 kg/m2) overall and in patients of Asian race.

Results: Of the 7020 patients overall, 934 (13.3%) had BMI < 25 kg/m2 and 3621 (51.6%) had BMI ≥ 30 kg/m2; a total of 1517 (21.6%) were of Asian race. EMPA reduced all-cause mortality, CV death/HHF, and incident/worsening nephropathy in patients across BMI categories, with benefits being consistent between those with BMI < 25 kg/m2, 25 to < 30 kg/m2 and ≥ 30 kg/m2. The cardiorenal protective effects of EMPA were similar in Asians.

Conclusion: This subgroup analysis of EMPA-REG OUTCOME, in which 934 patients had BMI < 25 kg/m2 and 1517 were Asian, suggests that the beneficial cardiorenal effects of EMPA are not affected by BMI, either overall or in Asian patients specifically.