Napp Pharmaceuticals Research Articles

1105-P: The Effect of Canagliflozin on Alanine Aminotransferase (ALT) Levels: Data from the Association of British Clinical Diabetologists (ABCD) Nationwide Audit Programme

Background: Nonalcoholic fatty liver disease (NAFLD) is common amongst those with type 2 diabetes (T2DM). Alanine aminotransferase (ALT) is known to correlate with levels of liver inflammation and fibrosis. Recent data from our audit programme showed promising reductions in ALT with dapagliflozin. Our aim was to test the same hypothesis, that canagliflozin may improve ALT levels in patients with T2DM, therefore possibly providing benefit in NAFLD. Methods: Data were extracted from the ABCD nationwide audit programme and then stratified into 4 groups based on gender and elevated or normal baseline ALT levels using gender specific references ranges (Prati et al). Baseline and follow-up ALT measurements in the 12-month (6-18months) period were required as a minimum. Data were analysed using Stata 16. Results: 730 datasets were included with mean (±SD) age 61.3yrs (±10.8), 60.1% male, 76% Caucasian (where known), BMI 32.5kg/m2 (±6.5), baseline HbA1c 8.9% (±1.6%) and weight 97.6kg (±22.2) and were broadly similar across all 4 sub-groups. For the entire population, median ALT decreased by 3U/L (95% CI -2, -3; P<0.01). Both male and female subgroups with normal ALT at baseline showed no significant change in ALT. In those with raised ALT at baseline (female ≥19U/L; male ≥30U/L) a change in ALT of -8U/L (95% CI -6, -9U/L; P<0.001) in men and -4U/L in women (95% CI -2, -5; P<0.05). Kruskal-Wallis test confirmed the difference between all groups was significant to P<0.01. No statistically significant correlation was noted between change in weight and change in ALT, which may suggest a weight-loss independent mechanism. Conclusion: Our data show that ALT decreases with canagliflozin, similar to that demonstrated with dapagliflozin. This decrease is greatest in those with elevated baseline levels. Weight-loss is not a predictor of change in ALT suggesting a potential weight-loss independent mechanism. Disclosure T.S.J. Crabtree: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. A. Bickerton: None. K.H. Darzy: None. P. Winocour: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Sanofi. M.L. Cull: None. A. Strzelecka: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. I.W. Gallen: None. M. Yadagiri: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S.

2209-PUB: Factors Associated with Switching from Sulfonylureas (SUs) to Dipeptidyl Peptidase-4 Inhibitors (DPP-4i) among Individuals with Type 2 Diabetes in the United States

Background and Objective: Studies examining the prevalence of and factors associated with switching from sulfonylureas (SUs) to dipeptidyl peptidase 4 inhibitors (DPP-4i) in real-world settings are lacking. We assessed the factors associated with switching from SUs to DPP-4i in the United States (U.S.). Methods: The retrospective cohort study was conducted using the U.S. Clinformatics® Data Mart (2009-2018). Adults with type 2 diabetes (T2D) and newly prescribed at least two SU prescriptions were included. Eligible individuals were followed for two years after the initiation of SU. We compare individuals’ characteristics between those who switched from SUs to DPP-4i and those who continued with SUs without adding other antidiabetic drugs. Results: In the total of 119,107 new SU users, 74.4% discontinued SUs within two years while 25.6% continued with SUs. Among those who discontinued with SUs, 4.7% switched to DPP-4i, and 12.6% switched to other antidiabetic drugs. Additionally, in those who continued with SUs, about 49.8% did not add other antidiabetic drugs. Multivariate logistic regression showed that those who had higher likelihood of switching were younger, female, living in the South, prior use of DPP-4i, fewer antidiabetic drugs used before the initiation of SU, glyburide user (vs. glimepiride user), and with cardiovascular disease or depression. Conclusion: The discontinuation rate for SUs is high (74.4%). Factors associated with switching from SUs to DPP-4i may help providers make more informed treatment decisions or develop strategies based on different individuals’ characteristics to improve medication use. Disclosure X. Tan: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. L. Yang: Employee; Self; Merck & Co., Inc. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. R. Zhang: Employee; Self; Merck Sharp & Dohme Corp. D. Zhang: Employee; Self; Merck Sharp & Dohme Corp. S. Rajpathak: Employee; Self; Menarini Group. M. Yu: None. Funding Merck Sharp & Dohme Corp; Pfizer Inc.

1021-P: HbA1c Levels and Rates of Hypoglycemia with Insulin Degludec U200 and Insulin Glargine U300 Stratified by Renal Function Subgroups: Post Hoc Analysis from the CONCLUDE Trial

CONCLUDE was a randomized, open-label, treat-to-target trial in participants with T2D, who received basal insulin ± oral antihyperglycemic drugs (OADs) and had ≥1 baseline hypoglycemia risk factors, including moderate renal impairment. Participants were randomized to degludec U200 or glargine U300 (± OADs). CONCLUDE demonstrated no significant difference in the overall symptomatic hypoglycemia rate with degludec U200 vs. glargine U300 in the maintenance period (primary endpoint, tested for superiority). However, lower rates of nocturnal symptomatic and severe hypoglycemia in the maintenance period (exploratory secondary endpoints) were observed with degludec U200 vs. glargine U300. The current post-hoc analysis investigated these hypoglycemia endpoints and HbA1c stratified by baseline estimated glomerular filtration rate (eGFR) subgroups (<60, 60-<90, ≥90 mL/min/1.73 m2). Change in HbA1c from baseline to end of treatment and rates and rate ratios for all hypoglycemia endpoints were comparable across eGFR subgroups and to the primary analyses. No statistically significant interactions were found between the subgroups for the endpoints assessed (Table). Irrespective of renal function, degludec U200 and glargine U300 resulted in similar HbA1c, and hypoglycemia rates were consistent with the primary analyses. Disclosure T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diagnostics K.K. H.S. Bajaj: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Kowa Pharmaceuticals America, Inc., Novartis Pharmaceuticals Canada Inc., Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., mdBriefCase, Medscape, Merck Sharp & Dohme Corp., Novo Nordisk Inc. S.R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S. Other Relationship; Self; MannKind Corporation. T. Jia: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. D.C. Klonoff: Consultant; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., EOFlow, Fractyl Laboratories, Inc., Know Labs, LifeCare, Inc., Novo Nordisk Inc., Roche Diabetes Care. S. Ladelund: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. M.V. Hansen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S

1074-P: Nasal Glucagon Reversed Insulin-Induced Hypoglycemia in Adults with Diabetes: A Pooled Analysis

Background: Nasal glucagon (NG), a ready-to-use drug-device combination for treatment of severe hypoglycemia, contains 3 mg glucagon dry powder that is absorbed passively through nasal mucosa. We examined the efficacy and safety of NG compared to 1 mg injectable glucagon (IG) in reversing insulin-induced hypoglycemia in a global population of adults with T1D or T2D. Notably, this is the first analysis including pooled T2D data. Methods: Post-hoc analyses used data from 3 randomized, cross-over studies. Treatment success was defined as an increase in BG to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir BG within 30 min of receiving glucagon. Tolerability was assessed using treatment-emergent adverse events and a symptom questionnaire. Results: In the T1D+T2D pooled analysis, 99.5% (213/214) of NG and 100% (214/214) of IG patients achieved treatment success in a mean time (preparation time excluded) of 13 and 11 min, respectively. All NG T2D patients (N=41) achieved treatment success. NG and IG induced similar BG changes (Figure). NG and IG had similar incidences of nausea and vomiting, with NG having a higher rate of side effects related to nasal administration [headache (13% NG, 7% IG), nasal discomfort (4% NG, 1% IG), etc.]. Separate T1D and T2D analyses showed similar results as T1D+T2D. Conclusion: NG was efficacious and well-tolerated in reversing insulin-induced hypoglycemia in adults with T1D or T2D. Disclosure E.R. Seaquist: Advisory Panel; Self; MannKind Corporation, Zucara Therapeutics Inc. Other Relationship; Self; American Board of Internal Medicine, Endocrine Society, International Hypoglycemia Study Group. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. M.X. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. Y. Takita: Employee; Self; Eli Lilly Japan K.K. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Y. Nagai: Employee; Self; Eli Lilly Japan K.K. Stock/Shareholder; Self; Eli Lilly and Company. Y. Yan: Employee; Self; Eli Lilly and Company. M. Matsuhisa: Research Support; Self; Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Sanofi, Sysmex Corporation. Speaker’s Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sanofi K.K., Takeda Pharmaceutical Company Limited. Funding Eli Lilly and Company

927-P: Effect of Oral Semaglutide with or without Background SGLT2i in Patients with T2D: Subgroup Analysis of PIONEER 4

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLTi) are widely used to treat type 2 diabetes (T2D) but trial data on their combined use are limited. We report the first data on oral semaglutide in combination with SGLT2i. This was a post-hoc subgroup analysis of the 52-week, double-blind, double-dummy PIONEER 4 trial (NCT02863419), in which patients with T2D uncontrolled on metformin with or without SGLT2i were randomized 2:2:1 to once-daily oral semaglutide 14 mg, subcutaneous (s.c.) liraglutide 1.8 mg or placebo. Glycated hemoglobin (HbA1c) and body weight (BW) data presented are for the trial product estimand (on-trial product without rescue medication). In total, 183 (26%) of 711 patients were receiving SGLT2i treatment at baseline which continued throughout the trial. Subgroups of patients receiving SGLT2i had a lower percentage of females, slightly longer mean T2D duration and higher BW. Changes in HbA1c and BW were similar in patients receiving oral semaglutide or s.c. liraglutide with or without SGLT2i. Occurrence of most gastrointestinal adverse events was similar in patients on GLP-1RA with and without SGLT2i. In conclusion, improvements in HbA1c and BW after one year as well as safety profile were similar in patients on GLP-1RA with or without background SGLT2i. Disclosure R.E. Pratley: Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Janssen Scientific Affairs, LLC., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. R. Bauer: Employee; Self; Novo Nordisk A/S. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck & Co., Inc., vTv Therapeutics. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. E.B. Kreiner: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P.N. Laursen: Employee; Self; Novo Nordisk A/S. J.J. Meier: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S

1590-P: Effects of Second-Line Metformin Combination Therapies on Weight, HbA1c, and Risk of Hypoglycemia over 3 Years: The DISCOVER Study

Background: We used DISCOVER, a 3-year observational study of people with T2D, to assess the effects of second-line metformin combination therapies on weight, HbA1c level and risk of hypoglycemia. Methods: Adjusted changes from baseline in weight and HbA1c level at 6, 12, 24 and 36 months were assessed using linear mixed models. An interval censored analysis was used to assess the risk of hypoglycemia. Results: At baseline, 7613 patients from 37 countries received second-line therapy with metformin and a dipeptidyl peptidase-4 inhibitor (DPP-4i; 48.3%), a glucagon-like peptide-1 receptor agonist (GLP-1 RA; 2.4%), a sodium-glucose co-transporter 2 inhibitor (SGLT2i; 8.3%) or a sulfonylurea (SU; 40.9%). When used in combination with metformin, GLP-1 RAs, SGLT2is and DPP-4is were associated with greater weight loss than SUs at all time points (Figure). Beyond 12 months, changes in HbA1c from baseline were similar for all combinations. Patients prescribed metformin and an SU had a greater occurrence of hypoglycemia over 3 years (11.9%) compared with the other combinations (3.9-6.4%). Conclusions: A high proportion of patients received metformin and a DPP-4i or an SU as a second-line therapy. All combinations showed a similar reduction in HbA1c. However, combinations of metformin and an SU were associated with the highest risk of hypoglycemia and the lowest weight reduction. Disclosure K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. B. Charbonnel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; AstraZeneca. A. Cooper: Employee; Self; AstraZeneca. M.B. Gomes: None. L. Ji: None. P. Leigh: Employee; Self; AstraZeneca. Employee; Spouse/Partner; Merck Sharp & Dohme Corp. A. Nicolucci: Consultant; Self; AstraZeneca. W. Rathmann: Advisory Panel; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Research Support; Self; Novo Nordisk Inc. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. M.V. Shestakova: None. A. Siddiqui: None. F. Tang: Research Support; Self; AstraZeneca. H. Watada: Advisory Panel; Self; Abbott, Ajinomoto, Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Fuji Film, Janssen Pharmaceuticals, Inc., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Yakult. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. H. Chen: None. Funding AstraZeneca

2192-PUB: Treatment Satisfaction in People with Type 2 Diabetes (T2D) Receiving Basal Insulin (BI): Results from Real-World Studies and Randomized Controlled Trials (RCTs) with Insulin Glargine 300 U/mL (Gla-300)

BI analogs can help optimize glycemic control in people with T2D, but the patients’ satisfaction is key for acceptance and treatment adherence. ACHIEVE, REACH, and REGAIN were open-label real-world studies comparing Gla-300 with standard of care BI (ACHIEVE: insulin glargine 100 U/mL [Gla-100] or insulin detemir [IDet]; REACH and REGAIN: Gla-100, IDet, insulin degludec [IDeg] or neutral protamine Hagedorn). EDITION 1-3 and BRIGHT were open-label RCTs comparing Gla-300 with Gla-100 and IDeg, respectively. All studies were in people with uncontrolled T2D and used the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs; Table). In RCTs and real-world studies, initiating BI in insulin-naïve participants was associated with improved treatment satisfaction after 6 months (ACHIEVE, 12 months) and a reduction in the perceived frequency of hyperglycemia. Perceived hypoglycemia increased slightly from low baseline values. Similar findings were found in patients switching BI, with improved patient satisfaction and reduced perceived frequency of hyperglycemia after 6 months of treatment, and no change in perceived hypoglycemia. Initiating or switching BI in people with uncontrolled T2D can improve patient satisfaction, irrespective of baseline diabetes treatment. Disclosure S.B. Harris: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Canadian Institutes of Health Research, Eli Lilly and Company, Health Canada/First Nations and Inuit Health Branch, Janssen Pharmaceuticals, Inc., JDRF, Lawson Foundation, Novo Nordisk Inc., Sanofi. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Sanofi. F.J. Snoek: Advisory Panel; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Research Support; Self; Sanofi. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Applied Therapeutics, Sanofi US. F. Lauand: Employee; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A. Roborel de Climens: Employee; Self; Sanofi. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Funding Sanofi

1462-P: Baseline Gait Speed Can Predict Diabetes Incidence in Individuals with or at Risk of Knee Osteoarthritis: A Longitudinal Study Using Data from the Osteoarthritis Initiative

Introduction: The coexistence of Knee osteoarthritis (OA) and diabetes mellitus (DM) can be explained by shared risk factors such as age and obesity. Both conditions adversely affect gait speed, however, longitudinal studies investigating the relationship between gait speed and DM incidence in people with or at elevated risk for knee OA are lacking. Therefore, the aim was to investigate the association between baseline gait speed and risk of DM incidence among people with or at risk for knee OA. Methods: Participants from the osteoarthritis initiative, aged 45 to 79 years, who were at risk or had knee OA and followed up from baseline to 96-month visit were included. Self-reported diabetes was used over a 4-time points to identify DM incidence. Gait speed was measured at baseline using 20 meter walk test. Body mass index (BMI) was measured and included as a time-dependent covariate. Generalized estimating equations with logistic regression were utilized to examine the association between baseline gait speed and DM incidence. Results: Increased baseline gait speed was significantly associated with decreased odds of incident DM after adjustments for covariates (OR 0.52). The risk of DM incidence decreased 48% for each 0.1 m/s increase in gait speed at baseline for individuals with established or at risk of knee OA. Sensitivity analysis showed that the significant results were maintained with those at risk of OA (OR 0.45) but not in those with established knee OA. Conclusion: Increasing baseline gait speed in general was significantly associated with a lower risk of DM incidence over time. However, the association disappeared after adjustments for BMI in people with established knee OA, suggesting that the majority of this association might be explained by higher weight. Therefore, future research should examine closely the link between gait speed and well-defined DM risk using objective measures such as glucose level. Disclosure A.M. Alenazi: None. B. Alqahtani: None. M.M. Alshehri: None. A.D. Alanazi: None. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. V. Vennu: None. N.A. Segal: None. S.M. Bindawas: None.

1110-P: Effect of Raised Alanine Transaminase (ALT) Levels on HbA1c in the Association of British Clinical Diabetologists (ABCD) Nationwide Audits of SGLT2 Inhibitors (SGLT2i)

Introduction: Alanine transaminase (ALT) is an important marker for Nonalcoholic Fatty Liver Disease (NAFLD), and its levels are reduced following treatment with SGLT2i. However, how raised ALT levels and hence NAFLD affects HbA1c response to SGLT2i is not known. Methods: Data for this study was obtained from the ABCD nationwide audits of patients with type 2 diabetes started on SGLT2i. We used a gradient boosting machine learning algorithm (GBM) to identify if ALT is an important predictor of glycaemic response to SGLT2i. The results of the GBM model were confirmed using linear regression analysis where the absolute drop in HbA1c was modelled as a dependent variable with baseline ALT as independent variable adjusted for relevant covariates. Results: We studied 9,609 patients initiated on Empagliflozin (n=5061), Dapagliflozin (n=3711) or Canagliflozin (n=837). The mean age of the study population was 59(±10.3), 62% male with a mean weight of 96.6(±18.8), baseline eGFR 81(±11) and baseline HbA1c 9.06% (±1.62). At a median 5.8 months follow-up, the mean HbA1c drop was 0.81% and was similar in all three types of SGLT2i. The drop in HbA1c was 0.62%, 0.78% and 1.01% in 1st 2nd and 3rd quartiles of baseline ALT, respectively (P-Anova <0.0001). In the GBM analysis the important predictors of glycaemic response were baseline weight (relative influence (RI)=71%), and baseline HbA1c (RI= 7.2%), baseline ALT (RI= 5.6%) baseline creatinine (RI= 4.9%). The model accuracy was 0.73 (0.71-0.75) and area under the curve was 0.83. In the linear regression model, higher baseline ALT was associated with a larger drop in HbA1c (beta=0.007, P<0.0001) after adjustments for baseline weight, weight loss, baseline HbA1c, and duration of diabetes. Conclusion: Higher baseline ALT levels are associated with a more significant SGLT2 induced HbA1c drop and SGLT2 inhibitors and are likely to be more effective in those with NAFLD. Disclosure H. Deshmukh: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. K. Adamson: None. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals.

FRI0536 SERUM GOLIMUMAB CONCENTRATIONS AND ANTI-DRUG ANTIBODIES ARE ASSOCIATED WITH TREATMENT RESPONSE AND DRUG SURVIVAL IN PATIENTS WITH INFLAMMATORY JOINT DISEASES: DATA FROM THE NOR-DMARD STUDY

Background:Lack or loss of response to TNFα-inhibitors can be caused by subtherapeutic drug levels and anti-drug antibodies (ADAb). Knowledge about associations between clinical efficacy and drug levels as well as occurrence of ADAb is limited in patients with inflammatory joint diseases (IJD) treated with golimumab.Objectives:To identify the therapeutic target concentration and assess the frequency of ADAb in golimumab-treated patients with IJD.Methods:91 patients from the NOR-DMARD study with a clinical diagnosis of axial spondyloarthritis (n=41), rheumatoid arthritis (n=20) or psoriatic arthritis (n=30) starting treatment with golimumab, with an available biobank sample at 3 months follow-up, were included. Treatment response was defined by ASDAS Clinically important improvement in axial spondyloarthritis, EWULAR good/moderate response in rheumatoid arthritis and improvement of ≥50% in modified DAPSA (using 28 swollen/tender joint counts) in psoriatic arthritis. Serum drug concentrations were analysed in non-trough samples collected 3 months after treatment initiation, using an automated in-house target-based immunofluorometric assay. ADAb was measured with an inhibition assay that measures neutralising antibodies. The association between drug levels and treatment response was assessed by multivariable logistic regression (adjusted for age, sex and prior bDMARD (Y/N)). Drug-survival was assessed by Kaplan-Meier curves and Cox proportional hazard regression analysis.Results:Golimumab serum concentrations varied considerably between patients on standard dose (range 0.0-8.2 mg/L) with a median of 2.2 (IQR 1.0-3.5) mg/L. The proportions of responders after 3 months among patients with golimumab concentration <1.0, 1.0-3.9 and ≥4.0 mg/L, were 19%, 49% and 74%, respectively (Fig.1). The likelihood of response after 3 months of treatment was significantly higher among patients with serum golimumab concentration ≥1.0 mg/L compared to those with golimumab <1.0 mg/L (OR 5.8 (95% CI 1.7-19.7), P =0.005). The proportion of responders was highest among patients with golimumab concentrations ≥4.0 mg/L, but the difference in response between patients with concentrations ≥4.0 mg/L compared to 1.0-4.0 mg/L was not statistically significant (OR 2.1 (95% CI 0.6-7.1), P=0.24). We also found a higher rate of treatment discontinuation in patients with serum golimumab concentration <1.0 mg/L compared to ≥1.0 mg/L (HR 3.6 (95% CI 1.9-6.9), P <0.001) (Fig.2). ADAb were detected in 5 of 91 samples and were associated with lower drug concentrations. Only 1 out of 5 ADAb-positive patients was a responder at 3 months, and all 5 ADAb positive patients discontinued treatment within the first 14 months.Conclusion:Golimumab concentrations ≥1.0 mg/L were associated with improved treatment response and better drug survival, but our results also indicate that some patients might benefit from higher concentrations. ADAb were associated with lower drug concentrations and both reduced treatment response and drug survival. These findings suggest a rationale for personalised dosing guided by measurements of drug concentration and ADAb in golimumab-treated patients with IJD, which should be addressed in future randomised strategy trials.Disclosure of Interests:Johanna Elin Gehin Speakers bureau: Roche, David J Warren: None declared, Silje Watterdal Syversen Speakers bureau: Roche, Thermo Fisher, Elisabeth Lie: None declared, Joe Sexton: None declared, Liz Loli: None declared, Ada Wierød: None declared, Trine Bjøro: None declared, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Nils Bolstad Consultant of: Pfizer, Janssen, Speakers bureau: Orion Pharma, Napp Pharmaceuticals, Takeda, Roche, Novartis, Guro Løvik Goll Consultant of: Novartis, Pfizer, Speakers bureau: Abbvie, Biogen, Boehringer Ingelheim, Orion Pharma, Eli Lilly, Novartis, Pfizer, MSD, Roche, UCBTable 1.Change in FVC(ml) and DLCO% in the 6–12 months before and after different treatmentTreatment groupPre-TxPost-TxpR9.8% (11)FVCDLCO2015±74672.4±17.22024±80360.7±27.90.780.43CYC25.0% (28)FVCDLCO1853±58561.2±23.81796±57861.4±23.90.740.79R+CYC17.9% (20)FVCDLCO1901±66758.2±14.51922±67246.7±18.80.900.90Non-R, CYC47.3% (53)FVCDLCO2177±65746.7±18.82286±70445.8±19.60.470.69SubgroupUIP31.3% (35)FVCDLCO2053±72158.9±22.71949±72749.3±25.10.570.15Non-UIP68.8% (77)FVCDLCO(%)1908±60859.0±18.71961±65460.5±1850.530.46Table 2.Secondary outcome and multivariable Cox model for overall survival

129-OR: Abnormal Mitochondrial Activity in Pain Processing Regions of the Brain in Painful Diabetic Peripheral Neuropathy

Aims: The management of painful diabetic peripheral neuropathy (pDPN) is inadequate because the disease mechanisms are not fully understood. We assessed cerebral cellular bioenergetics using phosphorus magnetic resonance spectroscopy (31P-MRS) to determine whether high energy phosphate metabolite levels are altered in the pain processing regions of the brain in pDPN. Methods: A total of 66 subjects, 44 with type 2 diabetes (12 no-DPN, 13 painless-DPN and 19 pDPN) and 12 healthy volunteers (HV), underwent detailed clinical and neurophysiological assessments, and 31P-MRS brain imaging at 3-Tesla (Ingenia, Phillips Healthcare) with voxels placed over the right somatosensory cortex and the thalamus (TR 4s, TR 0.26ms, voxel size 21 x 21 x 40mm3). Measures reflecting cellular bioenergetics (mitochondrial function), ATP to phosphocreatine (PCr) and inorganic phosphate (Pi) ratios (ATP:PCr and ATP:Pi) were calculated. Results: There was a significant group effect in the ATP:PCr ratio at the thalamus (p=0.016) and somatosensory cortex (p=0.025). The ATP:PCr at the thalamus was significantly higher in the pDPN group (0.50±0.06) compared to HV (0.44±0.04, p=0.024) and no-DPN (0.42±0.07, p=0.006). Moreover, the ATP:PCr ratio at the somatosensory cortex was significantly higher in pDPN (0.48 ±0.1) compared to HV (0.38 ±0.1, p=0.035). In addition, the ratio correlated with the numeric pain score ratings during the MRI scan at both brain regions. Conclusions: This is the first study to use 31P-MRS to study cerebral energetics in human-DPN and peripheral painful neuropathies. We demonstrated significantly higher ATP:PCr ratios in patients with pDPN in the somatosensory cortex and thalamus, which correlated with pain severity. This is suggestive of increased cellular energy usage in pain processing regions of the brain, perhaps due to continuous nociceptive inputs. Altered cerebral phosphorus metabolite ratios may serve as a biomarker of neuropathic pain in diabetes. Disclosure G.P. Sloan: None. A. Anton: None. D. Selvarajah: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, Wörwag Pharma. Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, Napp Pharmaceuticals, Novo Nordisk Inc., Pfizer Inc. I.D. Wilkinson: None.

26-OR: Acute Declines in EGFR during Treatment with Canagliflozin and Its Implications for Clinical Practice: Insights from CREDENCE

Background: Canagliflozin (CANA) slows progression of chronic kidney disease (CKD) in people with type 2 diabetes. CANA also induces a reversible acute decline in estimated glomerular filtration rate (eGFR), which is believed to be a hemodynamic effect. Predictors of the initial decline and its association with long-term eGFR trajectories and safety outcomes are unknown. Methods: This post-hoc study of the CREDENCE trial included 4289 patients with type 2 diabetes and CKD who had eGFR measured at both baseline and week 3. Participants were categorized by percentage decline in eGFR at week 3: >10%, ≤10% to >0%, and ≤0%. Baseline characteristics associated with acute eGFR declines >10% were evaluated using logistic regression. Long-term eGFR decline and safety outcomes were estimated in each eGFR decline category by linear mixed effects models and Cox regression after adjustment for laboratory measures and medication use. Results: More participants in the CANA (956 [45%]) versus placebo (PBO) group (450 [21%]) had an acute eGFR decline >10% (p<0.001). A >30% decline occurred infrequently (89 [4%] with CANA and 39 [2%] with PBO; p<0.001). In the CANA but not in the PBO group, older age (OR CANA 1.17, 95% CI 1.05-1.31; per 10 years) and history of heart failure (OR CANA 0.77, 0.59-0.99) were associated with a higher and lower likelihood of an acute eGFR decline >10%, respectively (both p for interaction <0.05). Following the initial eGFR change, long-term eGFR trajectories as well as overall safety profiles were similar across eGFR decline categories (all p values >0.05). Results were consistent when other decline thresholds (>20%) were used and in subgroup analysis by baseline eGFR (30-<45, 45-<60, and 60-<90 ml/min/1.73 m2). Conclusions: Although acute eGFR declines >10% occurred in nearly half of all patients following initiation of CANA, the benefit of CANA compared with placebo was observed regardless of the acute eGFR decline and safety profiles were similar. Disclosure M. Oshima: Research Support; Self; Japan Society for the Promotion of Science Program for Fostering Globally Talented Researchers. M.J. Jardine: Other Relationship; Self; See Other Relationship field. R. Agarwal: Other Relationship; Self; AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant; Self; Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship; Self; Bayer AG, Novo Nordisk Inc., Vascular Dynamics. C. Cannon: None. D.M. Charytan: Advisory Panel; Self; Allena Pharmaceuticals, AstraZeneca, Merck & Co., Inc., PLC Medical. Employee; Self; BAIM Institute. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. R. Edwards: Employee; Self; Janssen. T. Greene: Other Relationship; Self; Janssen, Durect, and Pfizer. A. Levin: Consultant; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. B. Neal: Research Support; Self; Janssen Research & Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. C.A. Pollock: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support; Self; Diabetes Australia. Speaker’s Bureau; Self; AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship; Self; Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.C. Wheeler: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant; Self; AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker’s Bureau; Self; Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. H. Zhang: Employee; Self; Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. V. Perkovic: Other Relationship; Self; See Other Relationship field. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. Funding Janssen Research & Development, LLC

303-OR: Effect of Dapagliflozin on Risk for Fast Decline in EGFR: Analyses from the DECLARE-TIMI 58 Trial

SGLT2 inhibitors may lead to short term decrease in eGFR, with later stabilization and long-term reduction in the risk for end stage kidney disease. Fast decline (FD) in eGFR can be defined as a reduction of ≥3 ml/min/1.73m2/year and is associated with poor long-term renal prognosis. In this post-hoc analysis we studied the effect of dapagliflozin (dapa) on the risk for FD in the DECLARE-TIMI 58 trial. In DECLARE-TIMI 58, 17,160 patients with T2D and established or increased risk for CVD, with mean baseline eGFR of 85.2 ml/min/1.73m2, were randomized to dapa vs. placebo and followed for a median of 4.2 years. The risk for FD was compared between treatment arms. In the time frame of 0.5 years (after stabilization) to 4 years, the proportion of patients with FD was reduced with dapa vs. placebo (26.8% vs. 37.1% respectively, p<0.0001). This observation was persistent in all subgroups assessed (Table). The mean (SD) reduction in eGFR per year was 6.3 (3.7) vs. 0.0 (2.5) ml/min/1.73m2/year in the FD (N=4,788) vs. non-FD (N=10,224) patients. The proportion of patients with FD during the entire study period (i.e., 0-4 years) was reduced with dapa vs. placebo as well (33.6% vs. 37.0% respectively, p<0.0001). Dapagliflozin reduced the risk for FD in eGFR in a broad population of patients with T2D and either established or increased risk for CVD, but relatively preserved renal function, irrespective of patients’ baseline characteristics.

88-LB: Similar Efficacy and Safety of IGlarLixi When Initiated in Patients with Type 2 Diabetes (T2D) with or without Concomitant Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) Use in a Randomized Controlled Trial (RCT) and Real-World Setting

iGlarLixi, the once-daily fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, has been shown to robustly improve glycemic control in adults with T2D. To assess the effects of iGlarLixi with SGLT2i in T2D, we conducted subgroup analyses according to SGLT2i use in the following populations: 1) adults uncontrolled on GLP-1 receptor agonists (GLP-1 RAs) and oral antidiabetic drugs (OADs) switching to iGlarLixi in the 26-week LixiLan-G RCT (NCT02787551) and 2) adults switching to or adding iGlarLixi in a 6-month, retrospective real-world observational study using data from the U.S. Optum-Humedica electronic medical records database. Endpoints included change in HbA1c and hypoglycemia incidence and event rates. Across the studies, there were no major differences in baseline characteristics for those who initiated iGlarLixi while already using SGLT2i (N=346) and those initiating iGlarLixi without background SGLT2i use (N=1285). HbA1c reductions from baseline to week 26 and hypoglycemia incidence and event rates were similar for iGlarLixi regardless of SGLT2i use (Table). In conclusion, evidence from both RCT and real-world clinical settings support the efficacy and safety of iGlarLixi when used in combination with SGLT2i. Disclosure J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Ali: Advisory Panel; Self; Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Research Support; Self; Eli Lilly and Company, Gelesis. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Stock/Shareholder; Self; Amarin Corporation. J.J. Meier: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. F. Giorgino: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., LifeScan, Inc., MedImmune, Merck Sharp &amp; Dohme Corp., Roche Diabetes Care, Sanofi. Research Support; Self; Eli Lilly and Company, LifeScan, Inc., Takeda Development Centre Europe Ltd. C. Guja: Advisory Panel; Self; AstraZeneca, Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Servier. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. R. Lubwama: Employee; Self; Sanofi US. E. Souhami: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Blonde: Advisory Panel; Self; AstraZeneca, Gilead Sciences, Inc. Consultant; Self; Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Janssen Scientific Affairs, LLC., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Sanofi. Funding Sanofi

1029-P: Effectiveness of Premix Insulin (Premix) in Type 2 Diabetes (T2D): A Retrospective UK Cohort Study

NICE guidelines suggest premix as a treatment option for people with T2D with HbA1c ≥9 % uncontrolled by ≥2 oral antidiabetic drugs (OADs). This retrospective cohort study explored real-world evidence for glycemic control with premix. UK electronic medical record data from THIN database were captured for adults with T2D uncontrolled (HbA1c ≥9 %) on ≥2 OADs initiating premix (index date) from 1/1/2010 to 12/31/2016. Baseline data were collected 12 months pre-index and outcomes followed for 24 months. Glycemic control was assessed by time to first achievement of HbA1c target &amp;lt;7.5 % and change in HbA1c over time, and evaluated by baseline characteristics. The final cohort had 974 participants (mean age 62 years; 56% male; mean BMI 31 kg/m2; 27% overweight; 44% obese; 8% Class III obese; mean HbA1c 11.3 %). Common comorbidities were hypertension (64%), dyslipidemia (23%) and nephropathy (21%). Background medication included metformin (99%), DPP-4i (51%), TZD (42%), SU (19%) and SGLT2i (0.5%). Probability of first achievement of HbA1c target &amp;lt;7.5 % was highest at 3-6 months (18%), 14% at 6-9 months, 15% at 9-12 months, and lower from 12 to 24 months (Figure). Target achievement differed by baseline HbA1c, but not OAD use. Probability of achieving glycemic targets on premix at 6 months was low, with little additional clinical benefit beyond 12 months, suggesting a high unmet need for early and timely therapy intensification. Disclosure E.B. Jude: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc., Sanofi. Other Relationship; Self; Lilly Diabetes, Menarini Group. A. Ali: Advisory Panel; Self; Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Research Support; Self; Eli Lilly and Company, Gelesis. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Stock/Shareholder; Self; Amarin Corporation. R. Emral: Advisory Panel; Self; Lilly Diabetes, Merck Sharp &amp; Dohme Corp. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. N. Nanda: Advisory Panel; Self; Novartis AG. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc., Pfizer Inc., Sanofi. R. Lubwama: Employee; Self; Sanofi US. K.D. Palmer: Employee; Self; Sanofi. A. Shaunik: None. P. Raskin: None. F. Gomez-Peralta: Advisory Panel; Self; Abbott, Menarini Group, Novartis AG, Sanofi. Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novartis AG, Novo Nordisk A/S, Sanofi. C. Trescoli: None. Funding Sanofi

27-OR: Effect of Canagliflozin on Total Hospitalization for Heart Failure Events in Patients with Type 2 Diabetes and Chronic Kidney Disease

Background: The sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of first hospitalization for heart failure (HHF) in the CREDENCE trial. The prevention of recurrent events is important to patients, clinicians and payers. In this post-hoc analysis, we evaluated the effect of canagliflozin on total HHF events. Methods: The CREDENCE trial compared canagliflozin or matching placebo and followed patients for a median of 2.6 years. The study included 4401 participants with type 2 diabetes, substantial albuminuria and estimated glomerular filtration rate (eGFR) 30 to &amp;lt;90 ml/min/1.73 m2 receiving renin-angiotensin system blockade. Negative binomial regression models were performed to assess the effect of canagliflozin on the total number of HHF events. Results: The mean age of participants was 63 years, with a mean eGFR of 56.3 ml/min/1.73 m2, while 50% had a history of previous cardiovascular disease and 15% had a history of heart failure. During the trial, 230 people experienced 326 total HHF events, with 166 having 1 event, 43 having 2 events, 15 having 3 events, and 6 having ≥4 events; thus, 42% of those experiencing at least 1 event went on to suffer a recurrent event during the follow up. Canagliflozin reduced first HHF events by 39% (hazard ratio [HR], 0.61; 95% confidence interval [CI] 0.47-0.80; P &amp;lt;0.001; number needed to treat [NNT], 46; 95% CI 29-124) and total HHF events by 36% (event rates of 22.0 and 34.8 participants with an event/1000 patient-years with canagliflozin and placebo, respectively; incidence rate ratio [RR], 0.64; 95% CI 0.56-0.73; P &amp;lt;0.001). Conclusions: Canagliflozin significantly reduced first and recurrent HHF events. These findings provide further support for the benefit of continuing canagliflozin therapy after an index heart failure presentation to prevent recurrent HHF events. Disclosure J. Li: Employee; Self; George Institute. M.J. Jardine: Other Relationship; Self; See Other Relationship field. B. Neal: Research Support; Self; Janssen Research &amp; Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. C. Cannon: None. R. Agarwal: Other Relationship; Self; AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson &amp; Johnson, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant; Self; Alnylam, Merck &amp; Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship; Self; Bayer AG, Novo Nordisk Inc., Vascular Dynamics. D.M. Charytan: Advisory Panel; Self; Allena Pharmaceuticals, AstraZeneca, Merck &amp; Co., Inc., PLC Medical. Employee; Self; BAIM Institute. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. R. Edwards: Employee; Self; Janssen. T. Greene: Other Relationship; Self; Janssen, Durect, and Pfizer. A. Levin: Consultant; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. C.A. Pollock: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support; Self; Diabetes Australia. Speaker’s Bureau; Self; AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship; Self; Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.C. Wheeler: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant; Self; AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker’s Bureau; Self; Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. H. Zhang: Employee; Self; Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. V. Perkovic: Other Relationship; Self; See Other Relationship field. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson &amp; Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. C. Arnott: Employee; Self; George Institute for Global Health. Funding Janssen Research &amp; Development, LLC

2009-P: Improvement in Renal Function Associated with Endobarrier (EB)–Induced Weight Loss

EB, a 60 cm proximal intestinal liner, endoscopically-implanted for up to 1 year, reduces weight and HbA1c. As the risk of progressive kidney-disease is increased by high BMI, we assessed the impact of EB on renal function. In 89 consecutive patients (aged 51.2 ± 8.0 years, 48.3% male, 55.1% europid, diabetes duration 10.8 (7.0-16.7) years, BMI 41.3 ± 6.9 kg/m2), mean ± SD HbA1c fell by 1.9 ± 1.8 %, from 9.4 ± 1.9 to 7.5 ± 1.2 % (p&amp;lt;0.001), weight fell by 15.0 ± 8.3 kg from 119.1 ± 26.3 to 104.1 ± 27.0 kg (p&amp;lt;0.001), systolic blood pressure (BP) from 138.4 ± 15.5 to 126.3 ± 16.9 mmHg (p&amp;lt;0.001) (Table 1a). With regard to renal function, mean ± SD serum creatinine improved by 5.0 ± 15.5 μmol/L from 88.9 ± 41.8 to 83.9 ± 42.1 μmol/L (p=0.003) and estimated-Glomerular-Filtration-Rate (eGFR - abbreviated MDRD equation) improved by 6.5 ±10.7 ml/min/1.73m2 from 83.6 ± 23.4 to 90.1 ± 25.7 ml/min/1.73m2 (p&amp;lt;0.001) (Table 1b). Eight patients had raised serum creatinine (&amp;gt;133μmol/L) prior to EB; after implantation in 6 of these, creatinine reduced and in 3 creatinine normalised. It was noteworthy, that the 6 patients with renal impairment who sustained improvement had large weight loss (mean 17.3 kg), whereas the patients without improvement had lower weight loss (mean 6 kg). As well as previously documented improvements, in weight, HbA1c and BP, EB was associated with improvements in renal function. These observational findings warrant further investigation. Disclosure R.E.J. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. M. Yadagiri: None. S.P. Irwin: None. W. Burbridge: None. R. Allden: None. T. Bashir: None. J. Bleasdale: None. E. Fogden: None. M. Anderson: None. P. Sen Gupta: None. P. Cockwell: Speaker’s Bureau; Self; Napp Pharmaceuticals.

1188-P: Approaches to and Inertia in Cardiovascular and Renal Risk Management of Type 2 Diabetes Patients in Primary Care: Results from a Global Quantitative Survey

Background: Despite recent recommendations for the use of glucose-lowering therapies with additional cardiovascular (CV) and renal benefits, as demonstrated through CV outcomes trials (CVOTs), many patients (pts) with type 2 diabetes mellitus (T2D) managed in primary care remain on therapeutic regimens now considered suboptimal. This global survey of primary care physicians (PCPs) investigated current approaches to early CV and renal risk management of pts with T2D. Methods: This web-based, global, quantitative panel survey of PCPs and primary care diabetes specialists (PCDSs) constituted 20 demographic, Likert scale, and multiple-choice questions covering the current management of pts with T2D, particularly the use of second/third line therapies (sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors). Results: Globally, 1558 PCPs and 119 PCDSs from 18 countries completed the survey. Respondents saw a mean 132 pts with T2D per month and had treated pts with T2D for 17 years. Overall, 73% of PCPs and 72% of PCDSs were responsible for second/third line treatment initiation. The biggest barrier to second/third line treatment initiation identified by respondents was local healthcare systems/insurance companies restricting access to these therapies. Concerns over safety, pt disinterest, and difficulties in maintaining regular appointments were also identified as significant contributors to treatment inertia. Only 68% of PCPs and 52% of PCDSs were aware of data published from recent CVOTs, while 68% and 58%, respectively, stated they had changed their treatment decisions based on these trials. Conclusions: Significant barriers still prevent optimization of T2D pt care in the primary setting, including limited familiarity of PCPs and PCDSs with new CVOT data, treatment inertia, and access restrictions for second/third line treatments. Disclosure S. Brunton: Advisory Panel; Self; Abbott, Bayer U.S., Merck &amp; Co., Inc., Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Lilly Diabetes. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. F. Cos: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk A/S, Sanofi. G.F. Deed: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk Inc., Sanofi-Aventis. N. Kanumilli: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Novartis AG, Novo Nordisk A/S. Consultant; Self; Boehringer Ingelheim International GmbH, Sanofi-Aventis. Speaker’s Bureau; Self; Napp Pharmaceuticals. P.R. Kushner: Advisory Panel; Self; Abbott, AstraZeneca, Bayer U.S., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc. P.J. Lin: Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch + Lomb, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Mead Johnson Nutrition, Merck &amp; Co., Inc., Novo Nordisk Inc., Sun Pharmaceutical Industries Ltd. Other Relationship; Self; Elsevier. J. Nolte: Advisory Panel; Self; AstraZeneca. Funding AstraZeneca

533-P: Predicting Treatment Response in Painful Diabetic Neuropathy Using Magnetic Resonance Brain Imaging

Background: Painful diabetic polyneuropathy (DPN) is difficult to manage as treatment response is often varied. The aim of this study was to explore the central mechanisms to explain the variance in treatment response. Methods: Forty-five consecutive patients who received intravenous lidocaine treatment for painful DPN were screened. All subjects completed a treatment efficacy questionnaire. Twenty-nine patients (responders n=14 and non-responders n=15) along with 26 healthy controls subsequently underwent multimodal brain magnetic resonance (MR) imaging to acquire anatomical and resting state functional data (3T, Achieva, Phillips Healthcare). Results: There was no significant difference in age (p=0.53), pain duration (p=0.89), diabetes duration (p=0.19) and clinical parameters of neuropathy (TCNS, p=0.16 and NTSS-6, p=0.61) between responders and non-responders to lidocaine treatment. Neither was there a difference in the use of concurrent neuropathic pain treatments. Non-responders to lidocaine had significantly lower mean S1 cortical volumes and mean number of vertices compared to responders and healthy controls (ANOVA p=0.02 and 0.02 respectively). There was no significant difference in S1 cortical volumes or vertices between responders and healthy controls. There was significantly greater resting state functional connectivity in lidocaine responders between the insula cortex [F(4)(13)=10.33; p-FDR=0.01] and the orbital frontal cortex [T(20)=3.88; p-FDR=0.02], amygdala [T(20)=3.65; p-FDR=0.02] and anterior cingulate gyrus [T(20)=4.04; p-FDR=0.01]. Conclusion: To the best of our knowledge, this is the first assessment of CNS mechanisms of treatment response in painful DPN. Key nociceptive processing areas showed decreased grey matter density (S1 cortex) and reduced functional connectivity (insula) relating to treatment response. MR neuroimaging may serve as a Central Pain Signature which could be used to predict treatment response. Disclosure K. Teh: None. I.D. Wilkinson: None. G.P. Sloan: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, Wörwag Pharma. Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, Napp Pharmaceuticals, Novo Nordisk Inc., Pfizer Inc. D. Selvarajah: None. Funding European Foundation for the Study of Diabetes; University of Sheffield

278-OR: Efficacy and Safety of Anti-interleukin (IL)-21 in Combination with Liraglutide in Adults Recently Diagnosed with Type 1 Diabetes

Objective: To evaluate the effect of anti-IL-21 and liraglutide, alone and in combination, compared to placebo, on preservation of β-cell function after 54 weeks of treatment in adults with recently diagnosed type 1 diabetes. Methods: This was a multicenter, double-dummy, double-blind, efficacy, safety and pharmacokinetic randomized control trial (NCT02443155) in adults recently diagnosed with type 1 diabetes and non-fasting C-peptide peak ≥0.2 nmol/L, comprising a 54-week treatment period followed by a 26-week observation period. Primary endpoint: area under the curve (AUC)0-4h for meal-stimulated C-peptide at week 54 relative to baseline. Results: At week 54, combination treatment was associated with a significant improvement of 48% in meal-stimulated C-peptide secretion versus placebo (Table). The insulin requirement was significantly lowered by 0.13 U/kg. Trends for better glycemic control and lower risk of hypoglycemic episodes at 54 weeks compared to placebo were also observed. No safety concerns were identified. Treatment benefits were not sustained at 26 weeks after end of treatment. Conclusion: Treatment with anti-IL-21 and liraglutide for 54 weeks was safe and resulted in sustained insulin secretion and lower insulin dose. Trends for improved glucose control and fewer hypoglycemic episodes compared to placebo were observed. Disclosure M.G. von Herrath: Employee; Self; Novo Nordisk A/S. S.C. Bain: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; AstraZeneca. B.W. Bode: Advisory Panel; Self; InPen, Medtronic. Consultant; Self; ADOCIA, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Pfizer Inc. Research Support; Self; Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Gan &amp; Lee Pharmaceuticals, Medtronic, Novo Nordisk A/S, Provention Bio, Inc., Senseonics, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., InPen, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Sanofi, Senseonics, Xeris Pharmaceuticals, Inc. Stock/Shareholder; Self; Glytec. J. Clausen: Other Relationship; Self; Novo Nordisk A/S. K. Coppieters: Other Relationship; Self; Novo Nordisk A/S. L. Gaysina: None. J. Gumprecht: Consultant; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier. Speaker&amp;#x2019;s Bureau; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier. T.K. Hansen: None. C. Mathieu: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intrexon, MannKind Corporation, Medtronic, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk Inc., Pfizer Inc., Roche Diagnostic USA, Sanofi. Research Support; Self; Intrexon, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk Inc., Sanofi. C. Morales Portillo: Board Member; Self; Novo Nordisk, Lilly, MSD, Astra, Sanofi, Abbot. Research Support; Self; Novo Nordisk, Sanofi, AstraZeneca, Pzifer, Lilly, Merck, Lexicon, FPS, Hanmi, Janssen, Boehringer, Takeda, Roche, Theracos. Speaker’s Bureau; Self; Sanofi, Novo Nordisk, AstraZeneca, Roche, Lilly, Boehringer, MSD, Ferrer, Janssen, Abbot. O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. S. Segel: Employee; Self; Novo Nordisk A/S. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. G.M. Tsoukas: Advisory Panel; Self; Amgen, Novo Nordisk Inc. Speaker’s Bureau; Self; Amgen Canada. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Roche Diagnostics K.K. Funding Novo Nordisk A/S