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Purpose: To evaluate the association between the eGFR trajectory and cardiovascular/renal outcomes in SGLT2i users. Methods: Cardiovascular and Renal Outcome Trials of SGLT2i with reports of eGFR change were included. Random-effect model was used. Results: In all, 7 RCTs were included. Meta-analysis showed that the risk of all-cause mortality was only reduced in SGLT2i users with eGFR change rate >-1ml/min/1.73m2 per year (RR=0.87, 95%CI, 0.77 to 0.99). Consistent risk reductions were observed in SGLT2i users in terms of heart failure, 3P-MACE (MI, stroke, CV death), 4P-MACE (3P-MACE and heart failure) and composite renal endpoints (sustained decline in eGFR, renal replacement treatment and renal death), regardless of eGFR change rate. Conclusions: The preserved eGFR decline may confer reduced risk of all-cause mortality but did not influence the benefits in cardiovascular and renal outcomes in SGLT2i users. Disclosure C. Lin: None. X. Cai: None. L. Ji: None. Funding Beijing Natural Science Foundation (7202216); National Natural Science Foundation of China (81970698, 81970708)

Microalbuminuria is thought to be a risk factor for progression to macroalbuminuria, an indicator of renal functional decline in patients with type 1 or 2 diabetes. However, it remains unknown which renal histological factors predict the onset of macroalbuminuria or eGFR Conclusions: Aggravated arteriolar hyalinosis is a histological risk factor for renal functional decline and predicts the onset of macroalbuminuria and CKD in patients with type 2 diabetes, normo-microalbuminuria, and normal renal function regardless of microalbuminuria grade. This finding might reflect initial changes in early diabetic nephropathy. Disclosure T. Moriya: None. A. Hayashi: None. A. Suzuki: None. M. Matsubara: None. M. Ouchi: None.

In EMPA-REG OUTCOME, empagliflozin (EMPA) reduced the risk of CV death by 38% in T2D patients (pts) with CV disease. EMPA induces an initial, reversible dip in estimated glomerular filtration rate (eGFR). We investigated whether this transient initial renal hemodynamic effect was influenced by baseline characteristics or had an impact on the EMPA-induced risk reduction in CV death. In a post-hoc analysis, among the 6,668 pts randomized to EMPA 10 mg, 25 mg or placebo [PBO] with eGFR available, 28.3% of EMPA pts vs. 13.4% PBO experienced an initial eGFR decline >10% from baseline to Week 4 (odds ratio [OR; 95% CI]: 2.7 [2.3-3.0]). Multivariate logistic regression was used to identify baseline characteristics predictive of eGFR dip >10%. The impact of an eGFR dip >10% on the risk reduction in CV death was assessed using Cox regression. Diuretic use and higher KDIGO (Kidney Disease: Improving Global Outcomes) risk category at baseline were predictive of an eGFR dip >10% with EMPA vs. PBO. Serious adverse events were generally lower or similar in EMPA vs. PBO, regardless of predictive baseline factors. EMPA-induced CV death risk reduction was consistent across subgroups below vs. above average eGFR dipping OR (Panel A) and not affected by eGFR dip >10% (Panel B). T2D pts with more advanced kidney disease and/or on diuretic therapy were more likely to experience an eGFR dip >10% with EMPA. EMPA reduced CV death, regardless of an initial eGFR dip >10%. Disclosure 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. B.J. Kraus: Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. M.R. Weir: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC., Merck & Co., Inc. G. Bakris: Consultant; Self; Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship; Self; Bayer AG, Novo Nordisk Inc., Vascular Dynamics. M. Mattheus: None. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk. N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. 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. I. Ritter: Employee; Self; Boehringer Ingelheim International GmbH. M. von Eynatten: Other Relationship; Self; Boehringer Ingelheim International GmbH. 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. C. Wanner: Advisory Panel; Self; Eli Lilly and Company, Merck & Co., Inc., Mundipharma International. Consultant; Self; Boehringer Ingelheim (Canada) Ltd., Sanofi Genzyme. Speaker’s Bureau; Self; AstraZeneca. Other Relationship; Self; Boehringer Ingelheim International GmbH. A. Koitka-Weber: Employee; Self; Boehringer Ingelheim International GmbH.

In participants with type 2 diabetes (T2D) in the REWIND trial, dulaglutide (DU) use for median follow-up of 5.4 years was associated with reduced composite renal outcomes, defined as the first occurrence of new macroalbuminuria, sustained decline in estimated glomerular filtration rate (eGFR) of ≥30%, or chronic renal replacement therapy. The objective of this post-hoc analysis was 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. Participants with T2D at cardiovascular (CV) risk 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. Sensitivity analyses were conducted by replacing the all-cause death component with CV or renal death, or renal death. 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 endpoint was significantly lower for the DU group compared with placebo (Table). 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 at CV risk. Disclosure J.E. Shaw: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mylan, Sanofi. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Eli Lilly and Company, Mylan. F.T. Botros: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R. Malik: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C. Atisso: Employee; Self; Eli Lilly and Company. H.M. Colhoun: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Novo Nordisk Inc., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Speaker’s Bureau; Self; Eli Lilly and Company, Regeneron Pharmaceuticals, Sanofi. Stock/Shareholder; Self; Bayer AG, Roche Pharma. Other Relationship; Self; Eli Lilly and Company, Sanofi. H.C. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Kowa Pharmaceuticals America, Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Sanofi. Funding Eli Lilly and Company

Objective: In type 2 diabetes(T2D), prevalence of chronic kidney disease (CKD) with normoalbuminuria is increasing. We assessed the annual eGFR decline rate (slope) in Japanese patients with T2D with CKD treated by sodium glucose transporter 2 inhibitor (SGLT2i). Methods: A total of 75 patients with T2D with CKD (eGFR Results: 1) Average initial (first month) eGFR drop values are as follows, in Norm/Micro (51.2 to 47.9ml/min/1.73m2: P10 ml/min/1.73m2/year) existed in 12.8% (5/39) and in 25.0% (9/36) respectively. Mean eGFR slopes in these rapid decliner were all improved and as follow, -12.2±2.1 to +1.2±3.4ml/min/1.73m2/year; P Conclusion: SGLT2i could still have a remarkable renal benefit in Norm/Micro diabetic kidney disease. Slope analysis might be useful for safety and detecting rapid eGFR decliner. Disclosure K. Kashima: None. H. Shimizu: None. M. Yamada: None.

SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) improve cardiovascular (CV) and renal outcomes through distinct mechanisms. However, evidence is lacking on clinical outcomes in patients treated with both classes. EXSCEL, the cardiovascular outcomes trial for the GLP-1 RA exenatide, provides an opportunity to explore CV and renal outcomes with dual GLP-1RA and SGLT2i treatment, as ∼10% of participants had an SGLT2i added to their glycemic management during follow-up. Cohorts of SGLT2i users in the exenatide arm were propensity-matched to: 1) users of exenatide but not SGLT2i; 2) placebo arm participants that did not take SGLT2i, based on last measured characteristics before SGLT2i initiation. Subsequent time-to-first adjudicated major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR decline was quantified in the matched cohorts using a mixed model repeated measurement (MMRM) analysis. Exenatide plus SGLT2i use numerically decreased the MACE hazard ratio and significantly reduced ACM risk, compared with exenatide alone and with placebo. The combination also significantly improved eGFR slope in both comparisons. This post hoc analysis offers support for the hypothesis that combinatorial exenatide and SGLT2i use may provide benefit on renal function and all-cause mortality. Disclosure L.E. Clegg: Employee; Self; AstraZeneca. R.C. Penland: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca, Novartis AG. D.W. Boulton: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca, Bristol-Myers Squibb Company. S. Bachina: Employee; Self; AstraZeneca. M. Thuresson: Consultant; Self; AstraZeneca. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. S. Gustavson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; AstraZeneca. C. Sjöström: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. J.A. Ruggles: Employee; Self; AstraZeneca. Stock/Shareholder; Self; Apple, AstraZeneca. A.F. Hernandez: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc. R.J. Mentz: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; GlaxoSmithKline plc. Other Relationship; Self; Amgen Inc., AstraZeneca, Bayer AG, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.

Background: DECLARE-TIMI 58 showed that dapagliflozin (dapa) a sodium glucose co-transporter 2 inhibitor (SGLT2i), reduced the rate of cardiovascular death or hospitalization for heart failure in patients with T2DM with or at high risk of atherosclerotic cardiovascular disease. SGLT2is have been shown to have a beneficial effect on renal outcomes. Methods: DECLARE-TIMI 58 pre-specified primary composite renal outcome (PCRO) included sustained 40% eGFR decline to < 60 ml/min/1.73m2, end-stage renal disease (defined as dialysis ≥90 days or kidney transplantation, confirmed sustained eGFR Results: A total of 17,160 subjects were enrolled, including 8,162 (47.6%) with eGFR ≥90, 7,732 (45.1%) with eGFR 60- Conclusion: In a large and broad population of patients with T2DM and mostly preserved renal function, dapa was associated with reduced progression of kidney disease and lower rates of clinically relevant renal events than was placebo. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. S.D. Wiviott: Consultant; Self; Aegerion Pharmaceuticals, Allergan, Angel Medical Systems, Inc., Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Clinical Research Institute, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, Icon Clinical, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Servier, St. Jude Medical, XOMA Corporation. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Amgen Inc., Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. T.A. Zelniker: None. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. J.P. Dwyer: Consultant; Self; Akcea Therapeutics, AstraZeneca, Bird Rock Bio, Eisai Inc., Goldfinch Bio, Sanofi-Aventis. A. Cahn: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, GlucoMe Ltd., Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Stock/Shareholder; Self; GlucoMe Ltd. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen Inc., AstraZeneca, Bristol-Myers Squibb Company, CVS/Caremark, Dyrnamix, Esperion, Intarcia Therapeutics, Inc., Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis. Research Support; Self; Amgen Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eisai Co., Ltd., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Takeda. I. Raz: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Consultant; Self; AstraZeneca, BOL, Bristol-Myers Squibb Company, CameraEyes Ltd, DarioHealth, Diabot, Exscopia, GlucoMe Ltd., Insuline Medical, Medial EarlySign, Orgenesis Ltd. Speaker's Bureau; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; BOL, CameraEyes Ltd, DarioHealth, Diabot, GlucoMe Ltd., Orgenesis Ltd. Funding AstraZeneca

Objective: The slope of eGFR decline is collecting attentions for earlier recognition of eGFR decliner. We analyzed the predictive value of maximum 1-year eGFR decline rate for the renal endpoint in prospective cohort. Research Design and Methods: We analyzed the data from EMPATHY trial which was the multicenter randomized control trial to assess the benefits of intensive statin therapy for patients with hypercholesterolemia and diabetic retinopathy. We calculated 1-year eGFR decline rate in every 6 months and analyzed its relation to the renal endpoint defined as initiation of chronic dialysis or increase in serum creatinine level by at least twofold. Results: The renal endpoint developed in 101 subjects out of 5,042 patients in mean follow-up 37 ± 13 months. The AUC of maximum 1-year eGFR decline rate by ROC was 0.960, that of albuminuria at baseline was 0.913, and that of eGFR at baseline was 0.809. When we defined the cut-off value of maximum 1-year eGFR decline rate as 20%, its sensitivity was 97.8% and its specificity was 80.2%. Time until the renal endpoint from the first demonstration of 1-year eGFR decline rate more than 20% was 353.1 ± 31.9 days. Conclusions: One-year eGFR decline more than 20% was highly associated with the renal endpoint. The renal endpoint was predominantly observed in the subjects with albuminuria. Disclosure S. Meguro: Research Support; Self; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., NIPRO Medical Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Y. Sato: None. H. Itoh: None.

Early initiation of insulin therapy often remains contentious due to various patient and physician-related barriers. Insulin is delayed by several years despite high A1c and is the foremost reason for costly future complications. In addition, the problem of early aggressive use of insulin depleting drugs causes β-cell fatigue leading to "brittle diabetes" and higher insulin dose requirements. In this observational cohort study, a comparison has been made between early insulin initiators (EII) (within 7-8 years of diabetes onset) and late insulin initiators (LII) (>8 years of onset), in terms of progression of CKD (eGFR decline), if any. A total of 200 subjects in each arm were matched at baseline for T2DM duration (16.78±4.32 year), BP, BMI, HbA1c and presence of co-morbid illnesses. Both groups were closely followed-up through our Diabetes Tele Management System based health care model that have previously shown to be successful in safely achieving glycemic targets compared to conventional models of care. A paired t test was done for analyzing the eGFR decline within each arm. EII arm required a significantly lower total daily dose of insulin (TDD) (average of 9 units/day) to maintain glycemic control throughout than the LII arm (average of 30 units/day). The decline in eGFR was significant in the LII arm, whereas in the EII arm, eGFR was maintained throughout. Change in A1c was also significant. Disclosure J. Kesavadev: None. R. Warrier: None. L. Ramachandran: None. A. Shankar: None. A. David: None. N.A. Ajai: None. G. Sanal: None. K. Thampiraj: None. G. Krishnan: None. S. Jothydev: None.

Background and Aims: We considered if deep learning (DL) models trained to predict diabetic retinopathy (DR) are also useful for prediction of renal disease in people with type 1 diabetes. Materials and Methods: We used 35000 retinal images and associated ground truth DR grades from the online Kaggle dataset. These were used to train a Resnet convolutional neural network (CNN) to predict the ground truth DR grades. The CNN was then applied to retinal images for each patient in the SDRNT1BIO available from the national screening program generating 10 DL outputs corresponding to DR gradings for both eyes. Longitudinal eGFR readings and risk factor data were available for the SDRNT1BIO through linkage to clinical records. Univariate associations of DL outputs with final eGFR at follow-up was tested via linear regression models. A penalised Bayesian approach using 10-fold cross-validation was used to select the most predictive DL features and assess prediction performance. Results: We found 7 DL outputs had a significant univariate association with follow-up eGFR adjusting for age, sex, duration of diabetes, baseline eGFR, and length of follow-up at p Conclusion: This small study demonstrates that retinal images contain information for predicting eGFR decline and that deep learning can extract this information. Future work on a larger dataset using DL to predict renal disease progression directly is therefore warranted. Disclosure J.C. Mellor: None. A.J. Storkey: None. H. Colhoun: Advisory Panel; Self; Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Regeneron Pharmaceuticals, Sanofi. Stock/Shareholder; Self; Bayer AG, Roche Pharma. P.M. McKeigue: Advisory Panel; Spouse/Partner; Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Sanofi. Research Support; Spouse/Partner; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis. Stock/Shareholder; Spouse/Partner; Bayer AG, Roche Pharma.

Body weight (BW) changes may affect muscle mass and thus creatinine (Cr) levels. Estimating glomerular filtration rate (eGFR) by Cr-based equations may not accurately reflect changes in kidney function when BW changes. Dulaglutide (DU) treatment was associated with BW loss and lesser eGFR (Cr-CKD-EPI) decline in people with T2D and moderate to severe CKD compared to insulin glargine (IG) (Table). The aim was to evaluate if the lesser eGFR decline observed with DU is related to BW loss. eGFR was evaluated with Cr-based equations (MDRD, CKD-EPI) compared to cystatin C-CKD-EPI equation. Cystatin C is not affected by muscle mass changes. CrCL was evaluated with the Cockcroft-Gault equation. BL characteristics were similar between treatments ([mean±SD] eGFR (Cr-CKD-EPI): 38.3±12.8 mL/min/1.73m2, A1c: 8.6±1.0%, age: 64.6±8.6 y, T2D duration: 18.1±8.7 y). All equations consistently show that eGFR remained stable with DU, but significantly decreased with IG regardless of BW loss in DU or gain in IG (Table). Since BW is a factor in CrCL calculations, compared to eGFR equations, BW loss in DU led to bias toward greater reductions in CrCL. This bias disappeared when using lean BW (Table). In conclusion, compared to IG, DU was associated with lesser eGFR decline in people with T2D and moderate to severe CKD regardless of BW changes. Disclosure K.R. Tuttle: Consultant; Self; Eli Lilly and Company, Boehringer Ingelheim GmbH, AstraZeneca, Gilead Sciences, Inc. M. Lakshmanan: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. B.L. Rayner: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Novartis AG, Servier. Advisory Panel; Self; AstraZeneca. R.S. Busch: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. A.G. Zimmermann: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. B. Woodward: Employee; Self; Eli Lilly and Company. F.T. Botros: Employee; Self; Eli Lilly and Company.

Aims: To investigate the association between estimated baseline glomerular filtration rate (GFR) and renal function decline in Chinese patients with type 2 diabetes with normoalbuminuria. Main Methods: A longitudinal study was performed on 368 Chinese patients with type 2 diabetes whose estimated GFR (eGFR) was determined at baseline with a 3.12-year follow-up. The patients were divided into three groups according to baseline eGFR (mL/min/1.73 m2): G1 (eGFR ≥ 120), G2 (90 ≤ eGFR < 120), G3 (60 ≤ eGFR < 90). The association between baseline eGFR and the renal function decline rate was assessed using binary logistic regression. Decliners were defined as a negative change ≥ −3.3% per year. Key Findings: Among G1 patients, the decliners were younger, had a higher baseline eGFR, shorter duration of diabetes, and lower diastolic blood pressure, compared with non-decliners. The G1 eGFR decline slope (% per year) was significantly higher than that in G2 and G3 patients. The percentage of decliners among G1 patients was significantly higher than that among G2 and G3 patients. Baseline eGFR group, HbA1c, hypertension history, and diastolic blood pressure were independent risk factors for progressive renal decline. Patients in the decliners group were more likely to progress to microalbuminuria and macroalbuminuria compared with those in the non-decliners group; however, the albuminruria progression percentage was not significantly different among G1, G2, and G3 decliners. Significance: Patients with baseline eGFR ≥ 120 mL/min/1.73 m2 had a higher risk for more rapid eGFR decline among Chinese patients with type 2 diabetes with nomalbuminuria. Disclosure J. Wan: None. H. Chen: None.

Background: EXSCEL was a multinational, randomized, blinded, placebo-controlled, pragmatic CV outcome trial of once-weekly exenatide on the background of usual care. We report exenatide’s impact on estimated glomerular filtration rate (eGFR), new macroalbuminuria and 2 renal composites from a prespecified analysis plan. Methods: Opportunistic local laboratory data were collected. Overall least squares mean difference (LSMD) eGFR (95% confidence interval [95% CI]) was calculated for 13844 patients with baseline and ≥1 follow-up value. Effect on new macroalbuminuria was estimated with a Cox regression model. Effects on renal composites were estimated with interval censored time to event models, with and without covariate adjustment (demographics and disease characteristics). Results: Intention-to-treat analyses showed no significant difference in eGFR levels with exenatide (LSMD +0.21 [-0.27, 0.70] mL/min.1.73m2, p=0.39). New macroalbuminuria occurred in 2.2% and 2.5% of the exenatide and placebo groups (p=0.19). There was a 15% lower renal composite 2 adjusted risk with exenatide (p=0.027) (Table). Conclusions: A composite of 40% eGFR decline, renal replacement, renal death or new macroalbuminuria was significantly reduced in an adjusted analysis by the addition of exenatide in a broad range of people with type 2 diabetes. Other renal outcomes were numerically but not statistically improved with exenatide. Disclosure M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. R.J. Mentz: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. P. Merrill: None. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. N. Iqbal: Employee; Self; AstraZeneca. N. Jakuboniene: None. B.G. Katona: Employee; Self; AstraZeneca. Y. Lokhnygina: None. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc.. A.P. Maggioni: None. P.K. Ohman: Employee; Self; AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. A. Ramachandran: None. T. Tankova: None. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. A.F. Hernandez: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca.

Background: NHANES data (2009-2014) suggests that 25% of U.S. adults with diabetes have CKD (eGFR < 60 ml/min/1.73m2 or ACR ≥ 30 mg/g). However, prevalence may be different among patients evaluated in clinical practice or in adults with T1D compared to T2D. Methods: We utilized a clinical laboratory database maintained by LabCorp® to assess CKD prevalence and classified risk (low, moderate, high or very high) based on KDIGO criteria. The population included 48,036 adults with T1D and 1,461,915 with T2D who had both an ACR and a CKD-EPI eGFR between August 2014 and August 2017. Rates of eGFR decline were calculated for patients with ≥ 3 eGFR results over at least a 1 year period. Results: CKD prevalence was 40% higher in T2D than T1D (44.3% vs. 31.6%, p 300, was uncommon (T1D: 7.8%, T2D: 8.3%); the majority with MA had an eGFR ≥ 60 (T1D: 60%, T2D: 53%). Median eGFR decline (ml/min/year) was low in the entire population (T1D: -0.6, T2D: -0.8), and in patients with ACR < 30 (T1D: -0.34, T2D: -0.47) or ACR 30-300 (T1D: -0.97, T2D: - 1.06). However, median annual rates of decline in patients with MA were -3.80 in T1D and -3.58 in T2D. Conclusions: These findings suggest that CKD prevalence and risk are higher in T2D than T1D among adult patients recently evaluated in U.S. clinical practices. Although MA is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1D and T2D. Availability of a large clinical laboratory database may add value when eligibility criteria, enrichment strategies, study endpoints or feasibility are assessed in clinical trials of patients with diabetes and CKD. Disclosure M. Cressman: Employee; Self; Covance Inc. J.L. Ennis: Employee; Self; LabCorp. Stock/Shareholder; Self; LabCorp. B.J. Goldstein: Employee; Self; Covance Inc.. L. Gourgiotis: None. D. Luo: None. M. Puri: Employee; Self; Covance Inc.. B. Gillespie: None.