Janssen Pharmaceuticals Research Articles

816-P: Predictors of Adherence and Persistence to Basal Insulin Therapy in Adults with Type 2 Diabetes

Objectives: Treatment adherence and persistence lead to gaps in achieving glycemic control in type 2 diabetes (T2D). We sought to identify predictors of adherence and persistence to basal insulin therapy among adults with T2D initiating therapy. Methods: Commercially insured US adults with T2D initiating basal insulin treatment between January 1, 2016 and December 31, 2018 were identified using IQVIA PharMetrics® Plus claims data. Adherence and persistence were quantified based on basal insulin claims in the one-year follow-up period and established definitions. Logistic regression models were developed to identify predictors of adherence and persistence based on baseline clinical and demographic information. Results: Among the 64,953 patients sampled, medication adherence and nonadherence (42% and 58%) and medication persistence and non-persistence (57% and 43%) were identified. Older age at baseline, oral and injectable antidiabetic medicine use, and physician office visits were associated with increased persistence and adherence; baseline hospitalization and emergency room visits were associated with decreased levels. Conclusions: Multiple predictors of adherence and persistence with basal insulin therapy were identified. These findings may help guide therapeutic choices and research priorities to bridge the gap between achievable efficacy of insulin therapy and real-world effectiveness. Disclosure V.R.Aroda: Consultant; Applied Therapeutics Inc., Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Applied Therapeutics Inc., Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Sanofi. N.F.Nielsen: Employee; Novo Nordisk A/S, Coloplast A/S. K.K.Mangla: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. Y.Wang: None. T.Namvar: None. J.R.Rajpura: Employee; Novo Nordisk.

803-P: Superior Glycemic Control with Once-Weekly Insulin Icodec with a Dosing Guide App vs. Once-Daily (OD) Basal Insulin Analogs in Insulin-Naïve T2D—ONWARDS 5

ONWARDS 5 (NCT04760626), a 52-week, open-label, randomized, phase 3a trial with real-world elements, assessed effectiveness and safety of once-weekly insulin icodec with a dosing guide app (icodec) vs OD basal insulin analogs (degludec, glargine U100 or glargine U300) in insulin-naïve adults with T2D. Participants (mean: 59.3 yrs; 32.8 kg/m2) were randomized 1:1 to icodec or OD analogs. The dose guidance app aided icodec titration; OD analogs were titrated as per standard of care. Estimated mean A1C change from baseline (BL) to week 52 was greater with icodec (-1.68%-points, BL 9.0%) vs OD analogs (-1.31%-points, BL 8.9%) confirming non-inferiority (p<0.0001) and superiority (p=0.009) of icodec vs OD analogs. Patient-reported outcomes (DTSQ and TRIM-D) were statistically significant in favor of icodec vs OD analogs at week 52. Rates of level 2 (<54 mg/dL) or level 3 (severe) hypoglycemia were low for both treatments (0.19 [icodec] vs 0.14 [OD analogs] events per person-year of exposure). There were no significant differences between treatments in time to treatment discontinuation/intensification. Overall, icodec with a dosing guide app showed superiority in A1C reduction, and significant improvement in treatment satisfaction and compliance scores vs OD analogs, with low hypoglycemia rates, in insulin-naïve adults with T2D in a real-world setting. Disclosure H.S.Bajaj: Research Support; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Anji Pharmaceuticals, Eli Lilly and Company, Kowa Company, Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Tricida, Inc. J.Aberle: Advisory Panel; Novo Nordisk, Speaker's Bureau; Novo Nordisk. M.J.Davies: Advisory Panel; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Lexicon Pharmaceuticals, Inc., Pfizer Inc., Medtronic, ShouTi Pharma Inc., Consultant; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Research Support; AstraZeneca, Novo Nordisk, Sanofi-Aventis U.S., Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc., Speaker's Bureau; Lilly, Boehringer-Ingelheim, Novo Nordisk, AstraZeneca, Napp Pharmaceuticals Limited, Novartis, Sanofi. A.M.Donatsky: Employee; Novo Nordisk. M.Frederiksen: Employee; Novo Nordisk A/S. D.Gogas yavuz: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. A.Gowda: Employee; Novo Nordisk A/S. I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. B.W.Bode: Advisory Panel; Ascensia Diabetes Care, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Research Support; Abbott Diabetes, Abvance Therapeutics, Better Therapeutics, Inc, Dexcom, Inc., Diasome, Dompé, Insulet Corporation, Lilly Diabetes, Medtronic, Novo Nordisk, Sanvita Medical, Senseonics, Provention Bio, Inc., REMD Biotherapeutics, ViaCyte, Inc., Xeris Pharmaceuticals, Inc., vTv Therapeutics, Speaker's Bureau; Abbott Diabetes, American Diabetes Association, Boehringer Ingelheim and Eli Lilly Alliance, Insulet Corporation, Lilly Diabetes, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; Glytec, LLC. Funding Novo Nordisk A/S

31-OR: Sex-Specific Differences in Subcutaneous Adipose Tissue in Persons with HIV May Contribute to Diabetes Risk

Background: Men with HIV have greater visceral adipose tissue (VAT) accumulation compared to women, which contributes to insulin resistance and derives, in part, from a failure to sequester lipids in subcutaneous adipose tissue (SAT). We assessed whether sex-specific differences in SAT composition are associated with measures of VAT volume and insulin resistance. Methods: Adults with HIV and consistent viral suppression on antiretroviral therapy had SAT and VAT measured by CT imaging, HOMA2-IR using fasting plasma glucose and insulin, and a subset had abdominal SAT lipoaspirates for single-cell RNA-sequencing to define proportions of CD4 and CD8 T effector memory cells (TEM), perivascular (PVM) and intermediate (IM) macrophages, and fibroblasts. Adjusted ordinal regression models and partial Spearman’s assessed the interaction between sex and cell proportions. Results: We enrolled 111 participants (24% female) with a median age of 48 years, BMI of 31.5 kg/m2, and HOMA2-IR of 3.0. VAT volume was significantly associated with HOMA2-IR. Women had lower VAT volumes and higher proportions of SAT PVMs and lower IMs, as well as fewer cytotoxic CD4 and CD8 T cells compared with men (p ≤ 0.05 for all). The proportions of SAT CD4 TEM, CD8 TEM, myofibroblasts, MYOC fibroblasts, and IMs were associated with VAT volume (p ≤ 0.05 for all), but an interaction by sex was not observed. The proportions of CD4 and CD8 TEM cells were significantly associated with HOMA2-IR and there was evidence of an interaction by sex status (interaction term p = 0.09 & p = 0.06, respectively). Conclusions: Women with HIV have a greater adjusted proportion of PVMs and lower cytotoxic CD4 and CD8 T cells in SAT. While the relationship between immune cell proportions and HOMA-IR only appeared to differ for CD4 and CD8 TEM cells, lower ectopic fat deposition in the context of reduced SAT inflammatory cells in women suggests the sex difference in diabetes risk among persons with HIV may relate to adipose tissue cellular composition. Disclosure S.Bailin: None. M.Mashayekhi: None. C.L.Gabriel: None. L.Hannah: None. S.Kalams: None. S.A.Mallal: None. J.A.Kropski: Advisory Panel; APIE Therapeutics, Research Support; Boehringer Ingelheim Inc., Bristol-Myers Squibb Company, Genentech, Inc. C.N.Wanjalla: None. J.Koethe: Advisory Panel; Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., Gilead Sciences, Inc., Theratechnologies, Research Support; Merck Sharp & Dohme Corp. Funding National Institutes of Health (R01DK112262, UL1RR024975, T32AI007474, P30AI110527)

1196-P: Offspring Being Overweight and Born Preterm Are More Common in Women Treated with Insulin Pump Compared with Multiple Daily Injections—A Large Prospective Cohort Study

Aims: Investigate glycemic control and risk of perinatal complications in women with type 1 diabetes (T1D) treated with insulin pump vs. multiple daily injections (MDI) during pregnancy. Methods: A secondary analysis of a prospective cohort of 2003 pregnant women. Odds ratios (OR) were estimated by logistic regression in crude and adjusted models for potential confounders. Results: In total, 723 women were treated with pump and 1280 were treated with MDI. At baseline (gestational weeks 8.6 (IQR: 7-10)) pump users had significant lower mean HbA1c (51.0 (10.2) mmol/mol (6.8 (0.9) %) vs. 54.2 (14.5) mmol/mol (7.1 (1.3) %), P < 0.001), longer diabetes duration (mean (SD) 18.3 (7.8) vs. 14.5 (8.3) years, p < 0.001) and higher prevalence of retinopathy (35.5% vs. 24.8%, p < 0.001). HbA1c in late pregnancy was similar (46.2 (9.4) mmol/mol (6.4 (0.9) %) vs. 46.4 (10.8) mmol/mol (6.4 (1.0) %), P=0.7458). Proportion of offspring being large for gestational age (LGA) was 59.0% (pump) vs. 52.2% (MDI) (adjusted OR 1.33 [95%CI 1.07;1.65], P=0.009) and born preterm 39.6% vs. 32.1% (adjusted OR 1.52 [95%CI 1.23;1.87], P=0.0001) (Table). No statistically significant difference was observed for other endpoints. Conclusion: Insulin pump treatment in pregnant women with T1D was associated with higher risk of LGA offspring and preterm delivery compared with MDI. Disclosure I.H.Thorius: Employee; Novo Nordisk A/S. L.N.Husemoen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. R.Baastrup nordsborg: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. A.Alibegovic: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. M.Gall: Employee; Novo Nordisk A/S. P.Damm: Other Relationship; Novo Nordisk A/S. J.Petersen: Research Support; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Vertex Pharmaceuticals Incorporated, Gilead Sciences, Inc. E.R.Mathiesen: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk.

1101-P: Glycemia after Pediatric Bariatric Surgery—Outcomes and Predictors

Background: Metabolic and bariatric surgery (MBS) is a safe and efficacious treatment for children and adolescents with severe forms of obesity. However, there are few data on the effects of pre-surgical fasting insulin homeostasis measures on post-surgical weight loss or glycemia. Methods: We analyzed data from n=216/242 individuals with ≥ Class 2 obesity prospectively enrolled in the multi-center, Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study for up to eight years. Individuals who had type 1 diabetes, a gastric band procedure, or lacked baseline data for insulin homeostasis measurements were excluded, leaving 216 individuals for analysis. Body composition was assessed through bioelectrical impedance measurements. An analysis of fasting markers of insulin homeostasis using homeostatic model of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), or HOMA-β and outcomes following MBS was performed. Results: Our cohort had a baseline mean age of 16.5 years, BMI of 52.7 kg/m2, and was 75.4% female. At 8-year follow up, participants had a mean BMI of 43.0 kg/m2. Pre-surgical measures of insulin homeostasis did not predict change in BMI or fat mass over eight years. However, larger improvements in HbA1c were positively associated with younger baseline age, higher baseline HOMA-IR and HOMA-β, and lower baseline HbA1c. Conclusion: Baseline markers of insulin homeostasis were not significantly associated with weight loss outcomes, but did predict glycemia 8 years after MBS. Disclosure S.Sisley: Speaker's Bureau; Rhythm Pharmaceuticals, Inc. A.S.Shah: None. K.J.Nadeau: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc., Lilly. T.Gu: None. M.Michalsky: Advisory Panel; Lilly, Other Relationship; Intuitive Surgical, Stock/Shareholder; Intuitive Surgical. T.M.Jenkins: None. T.Inge: None. Funding National Institutes of Health (U01DK072493); U.S. Department of Agriculture-Agricultural Research Service (3092-5100-065)

1115-P: Advanced Medical Therapy (AMT) for Youth-Onset Type 2 Diabetes (T2D)—Early Results from the Run-in Phase of ST2OMP

The Surgical or Medical Treatment for Pediatric Type 2 Diabetes (ST2OMP) study is a prospective open label clinical trial comparing metabolic bariatric surgery (MBS) to AMT for teens with youth-onset T2D. Prior to study group assignment, youth participate in a 6-month run-in period and receive AMT defined as multidrug, treat-to-target medical therapy to achieve an HbA1c <6.5%. Here, we examine the effects of AMT on metabolic parameters during run-in on the initial 51 participants. Participants in ST2OMP (57% female, 30% Black, 38% Hispanic, 25% White) were a mean age of 16.8 years, median diabetes duration 1.1 years, and median HbA1c 6.5% at screening (49% with HbA1c <6.5%). During run-in, metformin or pioglitazone use alone decreased (35.3% to 31.4%), as did insulin use (37.3% to 31.4%), while use of SGLT-2 inhibitors or GLP-1 agonists alone, or dual or triple therapy without insulin increased (21.6% to 31.4%). There was a small decrease in BMI, triglycerides and ALT, but a small increase in systolic and diastolic BP and total cholesterol, and decrease in HDL. At completion of run-in, 49% had an HbA1c of <6.5%. During a 6-month run-in period, AMT, using alternatives to insulin resulted in reduced need for insulin with favorable effects in some metabolic parameters, without worsening glycemic control. Full cohort recruitment and two-year follow-up in ST2OMP will determine the benefits of AMT vs. MBS. Disclosure A.S.Shah: None. A.Bailey: None. T.Inge: None. M.Helmrath: None. K.J.Nadeau: None. M.M.Kelsey: Other Relationship; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc., Lilly. T.M.Jenkins: None. L.R.Schaaf: None. S.Xanthakos: None. A.T.Trout: Consultant; Lantheus, General Electric Co., Research Support; Canon America Medical Systems, Siemens, Perspectum Ltd. A.Baumgartner: None. A.Riegler: None. N.Krishnan: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119450)

1001-P: Adherence and Persistence to Basal Insulin Therapy Is Associated with Decreased Health Care Utilization in Adults with Type 2 Diabetes

Objectives: Lack of adherence and persistence to prescribed therapy impact achievement of glycemic goals. This study aimed to assess the association between adherence and persistence to basal insulin therapy with healthcare resource utilization (HCRU) among adults with type 2 diabetes (T2D). Methods: This was an observational, retrospective cohort study of commercially insured US patients using IQVIA PharMetrics® Plus claims data. We identified adults with T2D initiating basal insulin therapy between January 1, 2016 and December 31, 2018. Adherence/non-adherence and persistence/non-persistence were assessed per established definitions. Demographic and clinical characteristics were assessed over the one-year baseline period (prior to initiation). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding by adherence and persistence status. Post-IPTW, all-cause medical HCRU and costs in the one-year follow-up period were compared across cohorts. Results: The final sample consisted of 64,953 patients: 42% and 58% met criteria for adherence and non-adherence, respectively; 57% and 43% met criteria for persistence and non-persistence, respectively. The proportion of patients with ≥1 hospitalization was lower for the adherence and persistence cohorts compared to their reference groups (adherence: 12.2% vs. 13.8%; persistence: 12.5% vs. 14.2%, both P<0.0001); for these patients, mean hospitalization days were lower among adherence and persistence cohorts (adherence: 10.1 vs. 13.2; persistence: 10.4 vs. 13.8, both P<0.0001). Total mean medical costs were also lower (adherence: $16,118 vs. $17,991; persistence: $16,459 vs. $18,399, both P<0.0001), driven by lower acute care costs (adherence: $6,210 vs. $7,775; persistence: $6,385 vs. $8,171, both P<0.0001). Conclusions: In this study, adherence and persistence to basal insulin therapy was associated with lower HCRU and costs, particularly for acute care. Disclosure N.F.Nielsen: Employee; Novo Nordisk A/S, Coloplast A/S. V.R.Aroda: Consultant; Applied Therapeutics Inc., Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Applied Therapeutics Inc., Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Sanofi. K.K.Mangla: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. V.Divino: Employee; IQVIA Inc. T.Namvar: None. J.R.Rajpura: Employee; Novo Nordisk.

147-LB: Visits in Pediatric vs. Adult Clinics for Young Adults (YA) with T1D—Prepandemic and Pandemic Care

Aim: YA with T1D have high risk of rising A1c and loss to follow up. To understand factors associated with visit frequency, we compared characteristics of YA with T1D seen in pediatric vs adult diabetes clinics in the pre- and pandemic periods. Methods: EMR data included YA, aged 18-30 yrs, with T1D in pediatric and adult clinics during the pre- and pandemic (4/1/19 to 3/15/20 and 3/30/20 to 3/15/21, respectively), for both inperson and telehealth visits. Results: There were 1,762 YA (54% male), aged 24.0±3.6 yrs, with T1D duration 13.4±6.3 yrs and A1c 8.2±1.6%; 61% were pump treated; 64% used CGM. Pre-pandemic, almost all visits were inperson while most pandemic visits were virtual. During the pandemic, proportion of virtual visits was greater in pediatric vs adult care (99% vs 90%, p<.001). Overall, pre-pandemic visit frequency was 3.5±3.4, reduced to 3.1±4.1 (p<.0001) during pandemic. Pre-pandemic visit frequency was higher in those with higher A1c (r =.18, p<.001) in pediatric and adult care. During pandemic, YA visit frequency was preserved across A1c groups only for those in pediatric care (Figure 1). Pandemic visit frequency was lower in adult care regardless of sex, pump, CGM or A1c. Conclusion: Maintaining visit frequency may mitigate glycemic deterioration in YA with T1D. Pediatric care likely maintained visit frequency through use of telehealth, highlighting need for hybrid care to optimize outcomes. Disclosure A. Shapira: None. L. J. Tinsley: None. E. Toschi: Advisory Panel; Eli Lilly and Company. L. M. Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. Funding Thomas J. Beatson, Jr. Foundation

193-LB: Refining Diabetes Risk for Individuals with Prediabetes

Rate of progression from prediabetes to diabetes varies greatly, and better risk stratification would help guide prevention efforts. We evaluated predictors of incident diabetes in the placebo arm (n=1212) of the vitamin D and type 2 diabetes (D2d) study. At baseline, participants met 2 or 3 ADA glycemic criteria for prediabetes (fasting glucose, FPG, 100-125mg/dL; 2-hour glucose during a 75-g OGTT, 2hPG, 140-199 mg/dL; HbA1c, 5.7-6.4%). Diabetes was diagnosed based on semiannual testing. After a median follow up of 2.5 years, 27% met criteria for diabetes. Among those who did and did not develop diabetes, mean BMI (±SD) was similar (32.1 kg/m2 ± 4.4), as well as other demographic factors including age, race, and ethnicity. More men than women developed diabetes (29% vs 23%, p=0.02). Incident diabetes rates differed by prediabetes subgroups (Figure); and those meeting all three prediabetes criteria at baseline (35.4%) were most likely to develop diabetes (log-rank p <0.001). There were no differences in the incident diabetes rate among those people meeting only 2 of the prediabetes criteria (Figure). Also, area under the receiver operator characteristic curves for incident diabetes at 36 months increased when all 3 criteria were used in the diagnosis (0.736) vs only FPG and HbA1c (0.686). We conclude that ‘prediabetes’ is heterogeneous, and the 2hPG may refine diabetes risk and guide intervention strategies in adults with high-risk prediabetes. Disclosure S. H. Kim: Advisory Panel; GI Dynamics, Consultant; Aligos, Research Support; Fractyl Health, Inc. D. S. Hsia: None. E. S. Leblanc: Other Relationship; Dexcom, Inc. M. Staten: None. R. Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. N. Rasouli: Research Support; Novo Nordisk, Eli Lilly and Company, Somalogic. V. R. Aroda: Consultant; Applied Therapeutics Inc., Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Applied Therapeutics Inc., Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Sanofi. A. G. Pittas: None. Funding National Institutes of Health (U01DK098245)

450-P: N-Terminal Pro-B Type Natriuretic Peptide Concentrations in Diabetic Cardiomyopathy—Baseline Data from the ARISE-HF Trial

Background: Diabetic Cardiomyopathy (DbCM) is a form of Stage B heart failure (HF). Concentrations of N-terminal pro-B type natriuretic peptide (NT-proBNP) may predict risk for HF progression in persons with DbCM. The ARISE-HF study (NCT04083339) is evaluating efficacy of AT-001, a highly selective aldose reductase inhibitor (AT-001) to improve exercise tolerance in affected patients. The aim of this analysis was to assess association between baseline NT-proBNP and cardiac status in type 2 diabetes participants with DbCM. Methods: Impaired exercise tolerance and baseline characteristics were evaluated in 679 patients with DbCM as a function of NT-proBNP at enrollment. Results: Median NT-proBNP in the overall study population was 71 ng/L (IQR 35-133). Baseline characteristics were similar across NT-proBNP concentrations, however, participants with higher NT-proBNP had higher left atrial volume (p<0.001) and higher right ventricular systolic pressure (p=0.04) on baseline echocardiogram. Higher NT-proBNP concentrations were associated with reduced physical activity reflected in lower PASE Score and a worse functional capacity reflected in lower peak VO2 (p<0.001) (Table 1). Conclusion: Among patients with DbCM, elevated NT-proBNP is associated with echocardiographic abnormalities and worse cardiac functional capacity and inversely associated with activity. Disclosure J.Butler: Consultant; Abbott,, Amgen, Applied Therapeutics, Array, Astra Zeneca, Bayer,, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharma,, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sequana Medical, Vifor, Speaker's Bureau; Novartis, Boehringer Ingelheim-Lilly, Astra Zeneca, Janssen. F.Zannad: Advisory Panel; BMS, Novo Nordisk, Pfizer Inc., Servier Laboratories, Other Relationship; Applied Therapeutics Inc., Bayer Inc., Boehringer Ingelheim and Eli Lilly Alliance, Merck & Co., Inc., Novartis. J.L.Januzzi: Consultant; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., AstraZeneca, Research Support; Applied Therapeutics Inc., Abbott, Roche Diagnostics, Novartis, Innolife Co., Ltd. S.Del prato: Advisory Panel; Abbott Diagnostics, Altimmune, Amarin Corporation, Applied Therapeutics Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Vertex Pharmaceuticals Incorporated, Novartis, Consultant; A. Menarini Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. J.Ezekowitz: Advisory Panel; Applied Therapeutics Inc. N.E.Ibrahim: None. C.S.Lam: Other Relationship; Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, Us2.ai. R.Perfetti: None. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. W.Tang: Consultant; Sequana Medical NV, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics LLC, Renovacor, Boston Scientific Corporation, Kiniksa Pharmaceuticals Inc, WhiteSwell Inc, CardiaTec Biosciences Inc, Other Relationship; American Board of Internal Medicine, Springer Nature, Research Support; National Heart, Lung, and Blood Institute. A.Urbinati: None.

108-OR: Clinical and Biochemical Factors Are Inversely Correlated in Diabetic Retinopathy and Age-Related Macular Degeneration

Although diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the two most common sight-threatening conditions in the elderly population, our understanding of the associated risks for these diseases have not been studied. Thus, we examined the association between AMD and DR in people with type 1 and type 2 diabetes from the Joslin 50-Year Medalist Study, composed of individuals who have had insulin-dependent diabetes for 50 years or longer and Beetham Eye Institute. In Medalists, there was an inverse association between DR severity and the presence of AMD (N=1163, P=<0.0001, AMD: 23.4%, 18.6, 7.9% for no-mild, moderate-severe, and proliferative DR, respectively). Similarly, the presence of AMD was associated with milder DR in the BEI cohort (N=58, P=0.004). There were no eyes with neovascular (severe AMD). The presence of AMD was associated with older age (P=0.03), increased diabetes duration (P<0.0001), less severe DR (P<0.0001), and the absence of neuropathy (P=0.003). In contrast, younger age (P=0.02) and the presence of neuropathy (P<0.0001) were associated with the presence of proliferative DR. Higher vitreous retinol-binding protein 3 (RBP3) to vascular endothelial growth factor (VEGF) ratios were associated with AMD and less severe DR in both postmortem Medalist and surgical BEI samples (N=187, P<0.05, all). The presence of milder DR was associated with increased risk of AMD development (24.8%, 10.0%, 5.0% for no-mild, moderate-severe, and proliferative DR, respectively, P=0.047), and risk of DR progression was decreased in eyes with versus without AMD (P=0.04) in a subset of Medalists with longitudinal follow up (22.9%). These novel findings that the inverse risk of DR and AMD is not likely due to similar pathogenic mechanisms and ageing factors. Further studies are needed to clarify the interactions between AMD and DR, that may provide new pathways to target against their development. Disclosure W.Fickweiler: None. G.L.King: Research Support; Janssen Research & Development, LLC. C.Jacoba: None. S.Jangolla: None. J.Gauthier: None. N.A.Ziemniak: None. I.Wu: None. J.D.Cavallerano: None. L.P.Aiello: Consultant; KalVista Pharmaceuticals, Inc., Novo Nordisk, MantraBio, Ceramedix, Research Support; Optos plc., Stock/Shareholder; KalVista Pharmaceuticals, Inc. J.Sun: Research Support; Adaptive Sensory Technology, Boehringer Ingelheim Inc., Roche Pharmaceuticals, Janssen Pharmaceuticals, Inc., Physical Sciences, Inc, Novo Nordisk, Optovue, Incorporated. Funding American Diabetes Association (7-21-PDF-022 to W.F.); National Eye Institute (R01EYE26080-01); National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK09433301); JDRF (17-2013-310); Dianne Nunnally Hoppes Fund; Beatson Pledge Fund

784-P: Characteristics of People with Young-Onset T2D in the SURPASS Program

Young-onset T2D, defined as diagnosed before age 40, is increasing around the world. Recent data suggest a faster deterioration in beta-cell function and earlier development of complications in this population, compared to later-onset T2D. This post-hoc analysis evaluated the baseline characteristics of people with young-onset vs later-onset T2D in the SURPASS clinical trial program. Baseline demographics and clinical characteristics were compared in participants with young-onset vs later-onset T2D from the SURPASS-1, -2, -3, and -5 clinical trials (N=4267). Analyses were performed by study. Across the SURPASS program, which included participants at various stages of T2D management, participants with young-onset T2D were younger, had longer duration of diabetes, worse glycemic control, higher mean body weight and BMI, and a worse lipid profile at baseline vs patients with later-onset T2D. Data from SURPASS-1 and SURPASS-2 also showed participants with young-onset T2D had greater insulin resistance (HOMA2-IR) at baseline. Despite their younger age at baseline, participants with young-onset T2D in the SURPASS program had an overall worse health status as compared to patients with later-onset T2D. Early intervention in young-onset T2D may be important to optimize long-term outcomes. Disclosure R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. P.Zeitler: Consultant; Eli Lilly and Company, Boehringer Ingelheim Inc., Johnson & Johnson. M.J.Davies: Advisory Panel; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Lexicon Pharmaceuticals, Inc., Pfizer Inc., Medtronic, ShouTi Pharma Inc., Consultant; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Research Support; AstraZeneca, Novo Nordisk, Sanofi-Aventis U.S., Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc., Speaker's Bureau; Lilly, Boehringer-Ingelheim, Novo Nordisk, AstraZeneca, Napp Pharmaceuticals Limited, Novartis, Sanofi. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. V.Thieu: None. C.Nicolay: Employee; Eli Lilly and Company. S.Allen: None. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

1162-P: Promoting Career Development of Physicians Engaged in Type 1 Diabetes (T1D) Research—The New DiabDocs Multicenter National K12 Program

Background: Given low rates of physicians entering diabetes research, NIH recently funded a multi-center National K12 “DiabDocs” Program to train and support physician-scientists for productive academic careers in T1D. Specific aims for the program include: 1) Expand the geographical access to diabetes K12 programs in the US, 2) Create a diverse nationwide cohort of promising physician-scientists through shared programmatic training experiences, 3) Develop a national mentor community, 4) Ensure consistency and effectiveness of mentoring, including focused attention on diversity, equity and inclusion. Methods: DiabDocs program administration is comprised of 2 Program Directors, an Executive Leadership Committee, a National Advisory Committee and Scientific Review Committee. Recruitment for the first cohort of program Scholars began in August 2022. Candidates self-nominated with a Letter of Intent (LOI). Eligible Scholars were then invited to submit a full application and attend a program retreat. Of the 12 LOIs received from 12 different institutions, 10 candidates were invited to submit a full application and attend the program retreat. At the retreat, 19 reviewers from 16 different institutions participated in diversity training, conducted interviews, and gathered as a study section to discuss applications. Results: Ultimately 4 scholars were selected: 2 with pediatric endocrinology and 2 with adult endocrinology backgrounds. Three scholars are women, and 1 scholar self-identifies as from a group underrepresented in medicine (25%). The next application cycle is planned for Jan-March 2023. Conclusions: The DiabDocs program will address the critical shortage of trained physician-scientists focused on T1D. We anticipate that the planned program training combined with existing research infrastructures will engage a talented and diverse pool of scholars and accelerate their career trajectories. Disclosure K.D.Dasani: None. L.Dimeglio: Advisory Panel; Merck & Co., Inc., Consultant; Abata Therapeutics, Vertex Pharmaceuticals Incorporated. F.K.Bishop: None. S.Golden: Advisory Panel; Abbott Diabetes, Medtronic. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. R.G.Mirmira: None. A.Steck: None. W.V.Tamborlane: None. S.M.Willi: Advisory Panel; Boehringer Ingelheim International GmbH, Medtronic. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K12DK133995)

797-P: Safety Profile of Once-Weekly Subcutaneous Semaglutide in a Real-World Adult Population with T2D

Real-world (RW) drug safety studies complement safety information from randomized clinical trials. This post hoc analysis of pooled data from nine global non-interventional studies (SURE program: 10 countries, ~30 weeks duration) investigated the safety and prescription patterns of once-weekly (OW) semaglutide in 3,505 adults with T2D in routine practice, overall and by patient subgroup and medical specialty stratification. All safety data reported by site physicians were collected and presented using descriptive statistics. Results: Tables 1 and 2. A two-fold increase in level-2 hypoglycemia was associated with insulin use and microvasculopathy. No new safety concerns were observed with OW semaglutide in this large, diverse, RW population with T2D; the safety profile was in line with that of phase 3 trials of semaglutide. Disclosure J.Yale: Advisory Panel; Sanofi, Novo Nordisk Canada Inc., Eli Lilly and Company, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Abbott, Mylan, Research Support; Sanofi, Novo Nordisk Canada Inc., Bayer Inc., Speaker's Bureau; Sanofi, Novo Nordisk Canada Inc., Eli Lilly and Company, Bayer Inc., AstraZeneca, Merck & Co., Inc., Boehringer Ingelheim (Canada) Ltd., Janssen Pharmaceuticals, Inc., Abbott, Dexcom, Inc. A.Major-pedersen: Employee; Novo Nordisk A/S. A.Catarig: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. R.Jain: Employee; Novo Nordisk Global Business Services, Stock/Shareholder; Novo Nordisk Global Business Services. M.Menzen: Advisory Panel; Boehringer Ingelheim Pharma GmbH&Co.KG, Novo Nordisk A/S, Ascensia Diabetes Care, Eli Lilly and Company, Novartis, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Santis, Boehringer Ingelheim Pharma GmbH&Co.KG, Novo Nordisk A/S, Bayer Inc., Eli Lilly and Company, Novartis. P.Holmes: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Novo Nordisk, Roche Diagnostics, Speaker's Bureau; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Bayer Inc. Funding Novo Nordisk A/S

776-P: Comparative Effectiveness of SC Semaglutide in Adults with T2D in U.S. Routine Clinical Practice—Year 1 Results of SEPRA, a Randomized Pragmatic Clinical Trial

SEPRA, a 2-year, ongoing, open-label, randomized, pragmatic study (NCT03596450) compares the effects of once-weekly SC semaglutide (sema) with physician's choice SOC when added to ≤2 oral antidiabetic medications for treatment intensification in US health-insured adults with T2D. The objective is to generate real-world evidence to support routine clinical decision making and complement clinical trial data. The primary endpoint is the proportion of patients who achieve HbA1c <7% at 1 year. Patients (N=1278) were randomized to receive sema according to label (n=644) or SOC excluding sema (n=634). All other treatment was per routine clinical care. Baseline characteristics were comparable (Table 1). Most common SOC medications were other GLP-1RAs (71.3%) and SGLT2is (15.5%). Sema dosing at 1 year was 26.6% at 0.25 mg, 30.4% at 0.5 mg and 24.4% at 1 mg (10.6% ended study and 7.6% not on sema at year 1). Use of sema resulted in a significantly greater proportion of patients achieving HbA1c <7% and body weight reduction vs SOC at 1 year (Table 1). A lower proportion of sema patients required additional treatment intensification in year 1 of the study vs SOC. No new safety concerns were identified. SEPRA demonstrates the superior effect of sema vs physician's choice SOC and that sema is an efficacious, durable treatment option in routine clinical practice. Disclosure J.B.Buse: Consultant; Alkahest, Anji Pharmaceuticals, AstraZeneca, Bayer Inc., Biomea Fusion, Inc., Boehringer Ingelheim International GmbH, CeQur SA, Cirius Therapeutics, Inc., Corcept Therapeutics, Eli Lilly and Company, GentiBio, Glycadia, Glyscend Inc., Janssen Pharmaceuticals, Inc., Mellitus Health, Pendulum Therapeutics, Praetego, LLC, Stability Health, Terns, Inc, Valo, Other Relationship; Novo Nordisk, Research Support; Dexcom, Inc., Novo Nordisk, vTv Therapeutics, Stock/Shareholder; Glyscend Inc., Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Praetego, LLC, Stability Health. B.P.Soule: Employee; Novo Nordisk. B.J.Harty: Research Support; Novo Nordisk. H.N.Christensen: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk A/S. M.J.Cziraky: Other Relationship; Novo Nordisk. V.Willey: Other Relationship; Novo Nordisk A/S. S.Skibsted: Employee; Novo Nordisk A/S. Funding Novo Nordisk

317-OR: Metabolomic Analyses Identify Novel Predictors of Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes

Background: Diabetic kidney disease (DKD) develops by young adulthood in up to 50% of people with youth-onset type 2 diabetes (Y-T2D), increasing risk of dialysis and premature death. Understanding mechanisms responsible for early DKD is key to management and prevention; accordingly, we sought to identify metabolite signatures of DKD in Y-T2D. Methods: We measured 57 metabolites in 374 baseline plasma and urine samples from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study, using mass spectrometry with a targeted ZipChip based assay. Urine albumin-to-creatinine ratio (UACR) was assessed annually for up to 15 years. Incident moderate and severe albuminuria were defined as UACR ≥30 and ≥300 mg/g, respectively, on ≥2 of 3 measures. We evaluated prediction of moderate and severe albuminuria in separate Cox proportional hazards models adjusted for HbA1c, triglycerides, systolic blood pressure, and estimated insulin sensitivity. Urine metabolites were normalized by urine creatinine. Results: Participants were 14±2 years of age, 37% male; 43% developed either moderate or severe albuminuria. Four urine metabolites predicted time to moderate albuminuria, while 8 urine metabolites predicted time to severe albuminuria, with 3 metabolites in common: 2-hydroxybutyric acid (moderate: HR: 0.82 per 1 SD [95% CI 0.70, 0.96]; severe: 0.70 [0.55, 0.88]), glycine (moderate: 0.81 [0.69, 0.94]; severe: 0.62 [0.45, 0.85]), citric acid (moderate: 0.78 [0.67, 0.91]; severe: 0.76 [0.58, 0.99]). Four plasma metabolites predicted time to moderate albuminuria and severe albuminuria, such as glutamic acid for moderate albuminuria (1.23 [1.03, 1.47]) and citric acid for severe albuminuria (1.39 [1.09, 1.77]). Conclusion: Higher urine metabolites involved in mitigating oxidative stress (glycine), glomerular epithelial cell injury (2-hydroxybutyric acid) and preserving mitochondrial function (citrate) predicted lower risk of albuminuria in Y-T2D. Disclosure L.Pyle: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. A.S.Shah: None. K.Drews: None. J.R.Ryder: None. R.Gubitosi-klug: None. K.Sharma: Advisory Panel; Reata Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. T.B.Vigers: None. L.El ghormli: None. I.De boer: Advisory Panel; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Boehringer Ingelheim International GmbH, Otsuka America Pharmaceutical, Inc., Bayer Inc., Consultant; George Clinical, Gilead Sciences, Inc., Medscape, Research Support; Dexcom, Inc. R.G.Nelson: None. S.Waikar: None. H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck & Co., Inc., Janssen Research & Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. N.White: None. K.L.Tommerdahl: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK61242)

387-P: High Incidences of Level 3 Severe Hypoglycemia Reported by T2DM Secretagogue-Users (iNPHORM, USA)

In the US, >90% of people with T2DM on oral antihyperglycemics use secretagogues. The present analysis is the first to quantify the real-world, US frequency of Level 3 severe hypoglycaemia (SH) in this population. Longitudinal, prospective data were leveraged from the iNPHORM study. Adults (≥18 years old) with secretagogue-treated T2DM (not on insulin) were recruited from a US-wide, probability-based internet panel. Data on participant characteristics and Level 3 SH occurrence were captured across a screener, baseline and 12 monthly follow-ups. Multivariable negative binomial regression with cluster bootstrapping for repeated measures modelled the annualized rate of SH for individuals completing ≥1 follow-up(s). A repeated lasso regression ‘voting’ procedure selected all risk factors. Multiple imputation addressed missingness. Of the 353 respondents (male: 51.1%; age: 54.6 [SD: 13.2] years; diabetes duration: 10 [IQR: 12] years; retention rate: 84.4%), the incidence proportion of SH over follow-up was 21.8 (95% CI: 17.8-26.3)%, and the rate was 3.8 (95% CI: 2.5-5.7) events per person-year. Our final model included age, continuous/flash glucose monitoring use, corticosteroid use, number of healthcare visits, fear of hypoglycemia, number of past-year SH requiring hospital care, retinopathy, and other diabetes complications. The rate of annualized Level 3 SH statistically increased with younger age, more frequent healthcare visits, greater fear of hypoglycemia, higher number of past-year healthcare-related SH, and presence of retinopathy. Our results indicate disturbingly high incidences of Level 3 SH among secretagogue users. Whenever logical and feasible, clinicians should prioritize one of the many other available antihyperglycemics that confer little to no hypoglycemia risk. Else, other hypoglycemia prevention strategies—risk-tailored to this ubiquitous T2DM population—are urgently warranted. Disclosure A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research. Funding Sanofi Global

1401-P: Psychotropic Drug Use in Children and Adolescents with Type 1 Diabetes

Psychiatric disorders in children and adolescents with type 1 diabetes (T1D) have caught increasing attention. While psychotropic drugs offer great value in managing psychiatric symptoms, their adverse effects engender considerable controversy regarding their use in pediatric patients, let alone in those with T1D. Despite the topic’s high visibility, little evidence exists on the patterns of psychotropic drug use in pediatric T1D patients. We thus conducted this cohort study of 3,720,381 children and adolescents (13,191 [0.36%] had T1D) using several Swedish national registers. We examined the trends and patterns (prescription source and treatment duration) of psychotropic drug use and estimated the risk of initiating psychotropic drugs after T1D onset. We found that psychotropic drug use increased significantly in children and adolescents with T1D from 2006 to 2019 (Figure 1), with ADHD medications, SSRI, hypnotics and anxiolytics among the most used ones. The primary prescription source was psychiatric care, and treatment durations were mostly <12 months (except for ADHD medications). Children and adolescents with newly-onset T1D had a higher risk of initiating any psychotropic drug (hazard ratio 1.29, 95%CI 1.20-1.38) than their peers without T1D. Our findings highlight the need for risk/benefit studies of psychotropic drugs among young users with T1D to inform future research and guideline development. Disclosure S.Liu: None. T.Lagerberg: None. J.F.Ludvigsson: Research Support; Janssen Pharmaceuticals, Inc., MSD Life Science Foundation. M.Taylor: None. B.Donofrio: None. P.Lichtenstein: None. S.Gudbjörnsdottir: None. A.Butwicka: None. Funding Swedish Research Council (2017-00788)

578-P: Effect of Two Timings for Postprandial Exercise Onset on Hypoglycemic Risk in Adults Living with Type 1 Diabetes

Introduction: To limit hypoglycemic risk of during postprandial aerobic exercise the importance of reducing prandial insulin dose have been established with exercise starting 90-min after the meal. People with type 1 diabetes also exercise closer or further away of their mealtime and hypoglycemic risk associated with those timings may be different. Objective: We aimed to evaluate the effect of two different timings for exercise onset (60-min vs. 120-min post-meal) during moderate intensity exercise. Methods: 37 participants (25 M/ 12 F; HbA1c: 7.4 ± 0.9%) received an ultra-rapid insulin dose reduced by 50% and performed 1 hour of continuous moderate intensity exercise (at 60% of VO2peak) started either 60-min (EX60min) or 120-min (EX120min) after breakfast. Venous blood glucose was measured every 10-min during exercise. Results: Decrease in blood glucose between exercise onset and nadir (lowest point during exercise) was more important with EX120min (-68.5 ± 43.2 mg/dL, EX60min vs. -75.7 ± 39.6 mg/dL, EX120min, p=0.015). The number of hypoglycemic events during exercise and during recovery (90-min post-exercise) were similar between EX60min and EX120min (3 vs. 4 and 3 vs. 0, respectively). Postprandial glucose excursion before exercise onset was reduced with Ex60min compared to Ex120min. Conclusion: For postprandial aerobic exercise, with a reduced insulin meal bolus, hypoglycemic risk is comparable if exercise is started at 60 or 120min after the meal. Guidelines established with exercise starting 90min after the meal can probably be used for earlier or later timing. Disclosure J.Molveau: None. É.Myette-côté: None. S.Tagougui: None. N.Taleb: Consultant; Viatris Inc. E.Heyman: None. C.Suppere: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation.

1238-P: The Face of Diabetic Cardiomyopathy—Baseline Characteristics from the ARISE-HF Trial

Background: Diabetic Cardiomyopathy (DbCM) is a severe complication of diabetes and a cause of heart failure (HF) occurring in the absence of other causes of cardiac dysfunction. Methods and Results: ARISE-HF (NCT04083339) is a global Phase 3 randomized study evaluating the safety and efficacy of a novel highly selective aldose reductase inhibitor (AT-001) versus placebo to improve exercise capacity in individuals with DbCM (defined by elevated cardiac biomarkers or structural/functional cardiac abnormalities along with impaired exercise capacity). Table 1 details the 684 study participants with DbCM in the study: 50% female, with a mean age 67.5 years. Glycemic control at enrollment was excellent (HbA1c of 6.99%). At baseline, the median NT-proBNP was 71 ng/L and hs-cTnT was 9 ng/L. Among echocardiographic abnormalities evaluated at enrollment, the most common were abnormal global longitudinal strain and impaired diastolic relaxation. Daily physical activity was low (mean PASE score of 154.3 + 89.6). Significant impairment in cardiac functional capacity was present at enrollment with a peak VO2 of 15.7 + 3.8 ml/kg/min. Conclusion: The ARISE-HF trial is an ongoing phase 3 clinical trial evaluating the safety and efficacy of aldose reductase inhibition on exercise capacity in patients with DbCM. The baseline analysis of the study cohort provides a unique characterization of individuals with DbCM. Disclosure J.Butler: Consultant; Abbott,, Amgen, Applied Therapeutics, Array, Astra Zeneca, Bayer,, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharma,, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sequana Medical, Vifor, Speaker's Bureau; Novartis, Boehringer Ingelheim-Lilly, Astra Zeneca, Janssen. F.Zannad: Advisory Panel; BMS, Novo Nordisk, Pfizer Inc., Servier Laboratories, Other Relationship; Applied Therapeutics Inc., Bayer Inc., Boehringer Ingelheim and Eli Lilly Alliance, Merck & Co., Inc., Novartis. J.L.Januzzi: Consultant; Boehringer Ingelheim Inc., Janssen Pharmaceuticals, Inc., AstraZeneca, Research Support; Applied Therapeutics Inc., Abbott, Roche Diagnostics, Novartis, Innolife Co., Ltd. S.Del prato: Advisory Panel; Abbott Diagnostics, Altimmune, Amarin Corporation, Applied Therapeutics Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Vertex Pharmaceuticals Incorporated, Novartis, Consultant; A. Menarini Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. J.Ezekowitz: Advisory Panel; Applied Therapeutics Inc. N.E.Ibrahim: None. C.S.Lam: Other Relationship; Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, Us2.ai. R.Perfetti: None. J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. W.Tang: Consultant; Sequana Medical NV, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics LLC, Renovacor, Boston Scientific Corporation, Kiniksa Pharmaceuticals Inc, WhiteSwell Inc, CardiaTec Biosciences Inc, Other Relationship; American Board of Internal Medicine, Springer Nature, Research Support; National Heart, Lung, and Blood Institute. A.Urbinati: None.