Bayer AG Research Articles

445-P: CV Risk Factor Control in Patients with T2D and Coronary Artery Disease vs. Stroke

Stroke and coronary artery disease (CAD) share several cardiovascular (CV) risk factors (RFs) , including type 2 diabetes (T2D.) RF control is vital for secondary prevention of both conditions, but systems for care of patients (pts) after stroke or CAD events differ, and distinctions in care for these pts have not been examined. We compared RF control in pts with CAD vs. stroke at baseline in 3 recent large CV outcome trials (OTs) involving 11,622 T2D pts at high CV risk.We analyzed baseline data from (1) EMPA-REG OUTCOME (2) CAROLINA and (3) CARMELINA. RFs assessed included dyslipidemia, hypertension, smoking, and use of anti-platelet/-coagulant drugs. RF control was defined as (a) LDL-C <100 mg/dL or statin use; (b) SBP <140 + DBP <90 mmHg; (c) use of anti-platelet/-coagulant; and (d) not smoking. The quality of CV RF goal attainment was defined as the odds of having 3-4 vs. 0-2 RFs controlled. We calculated the odds ratio across macrovascular disease groups at baseline and by subgroups of age, sex and region in the trials, based on logistic regression.The odds ratios (ORs) (95% confidence intervals [CI]) for RF control in pts with CAD alone was higher than in those with stroke alone across all 3 trials: (1) 2.60 (95% CI 2.19-3.08) ; (2) 1.59 (1.18-2.15) , and (3) 2.20 (1.81-2.67) , respectively. The respective ORs (95% CIs) were lower (and rendered non-significant in CAROLINA) when RF control in pts with both CAD and stroke was compared to those with stroke alone: (1) 2.00 (1.52-2.64) , (2) 1.13 (0.72-1.79) and (3) 1.42 (1.08-1.86) . Results were consistent across all subgroups.We found significant disparities in CV RF control based on history of CAD and/or stroke in 3 contemporary T2D CVOTs, with less optimal control in stroke pts, particularly in those with stroke alone. The intermediate results in those with both CAD and stroke suggest a role for clinician factors. These findings require further study to understand their origins but emphasize the need for improved secondary prevention strategies in pts with stroke. Disclosure P.Balasubramanian: None. W.Kernan: None. K.N.Sheth: Research Support; American Heart Association, Becton, Dickinson and Company, Biogen, National Institutes of Health. A.Ofstad: Employee; Boehringer Ingelheim International GmbH. M.Mattheus: Employee; Boehringer Ingelheim Pharma GmbH & Co.KG. N.Marx: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Genfit, Lilly, Merck Sharp & Dohme Corp., Novo Nordisk, Research Support; Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Speaker's Bureau; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. S.E.Inzucchi: Advisory Panel; Abbott Diagnostics, ESPERION Therapeutics, Inc., vTv Therapeutics, Consultant; Merck & Co., Inc., Pfizer Inc., Other Relationship; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk.

1222-P: Characteristics, Mortality, and Clinical Outcomes of Hospitalized Patients with COVID-and Diabetes: A Reference Single-Center Cohort Study from Poland

Introduction: Diabetes is a risk factor for severe COVID-course. In this one-center report, we assessed clinical characteristics and risk factors associated with unfavorable outcomes in diabetic patients (DP) hospitalized due to COVID-19. Methods: We retrospectively analyzed data from a cohort of patients with confirmed SARS-CoV2 infection admitted to the University Hospital in Krakow (Poland) , a regional reference center for COVID-19, between March 6th 2020 and May 15th 2021. The data was collected from electronic medical records. Results: We included 5191 patients, mean age 61.98±16.66 years, 2348 (45.2%) women, 1364 (26.3%) DP. DP were older as compared to non-diabetics (median age 70 vs. 62 years, IQR 62-77 and 47-72, p<0.001) with similar gender distribution. DP were characterized by higher mortality (26.4% vs. 15.6%, p<0.001) , longer hospital stay (median 15 vs. 13 days, IQR 10-24 and 9-20, p<0.001) , more frequent ICU admission (15.7% vs. 11%, p<0.001) and more frequent requirement for mechanical ventilation (15.5% vs. 11.3%, p<0.001) . When adjusted for sex and age, the relative risk for in-hospital death, ICU admission and mechanical ventilation was 1.32 (95%CI 1.13-1.54) , 1.4 (95%CI 1.17-1.69) and 1.3 (95%CI 1.08-1.57) , respectively. Multivariable logistic regression showed age, CRP and D-dimer level, history of heart failure, and loop diuretic use were associated with higher risk of death, whereas anticoagulation therapy, ACEI/sartan/mineralocorticoid receptor antagonist use and thiazide use were associated with lower risk. Conclusions: In this large COVID-cohort, DP constituted more than one fourth of hospitalized patients. Their risk of death was ca. 30% higher as compared to non-diabetics, as was the risk of other important clinical outcomes. We identified a number of clinical, laboratory and therapeutical variables associated with risk of hospital death in DP with COVID-19. Disclosure M.Kania: None. T.Klupa: Advisory Panel; Abbott, BIOTON S.A., Sanofi, Research Support; Medtronic, Speaker's Bureau; Ascensia Diabetes Care, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. P.W.Witek: Other Relationship; Abbott, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Medtronic, Merck & Co., Inc., Novo Nordisk, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH. B.Katra: None. M.W.Rajzer: Consultant; A. Menarini Diagnostics, Speaker's Bureau; Bayer AG, Boehringer Ingelheim International GmbH, EGIS Pharmaceuticals, Servier Laboratories. M.Malecki: Consultant; Abbott Diabetes, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Speaker's Bureau; Ascensia Diabetes Care, AstraZeneca, Bayer AG, Merck & Co., Inc., Mundipharma, Servier Laboratories. K.Mazur: None. M.Terlecki: None. Z.Chaykivska: None. M.K.Fiema: None. M.A.Kostrzycka: None. M.Kopka: None. M.Wilk: None. J.Hohendorff: Advisory Panel; Abbott. Funding The authors were supported by the Polish National Center for Research and Development grant (grant number SZPITALE-JEDNOIMIENNE/18/2020) .

1415-P: Risk–Benefit Data from the Worldwide EndoBarrier (EB) Registry

Uncertainty exists re risk:benefit of proximal intestinal exclusion with EB, a novel endoscopic duodenal jejunal liner device for obesity, both with and without diabetes. In view of this, during 2017, an independent, secure, on line registry was established under the auspices of the Association of British Clinical Diabetologists, for the collection of safety and efficacy data worldwide. As of December 2021, data had been entered on 10patients {age 52.1 ± 10.3 year, 53% male, 87% diabetes, BMI 41.1 ± 8.9 kg/m2} and showed many benefits (Table 1) . There were 43 (4.2%) SAEs and 139 (13.9%) less serious AEs (Table 2) . All SAE patients made a full recovery and most derived significant benefit. The benefits of EB therapy are likely to reduce the complications of diabetes. This international data from the EB registry suggests that the likely benefits of EB, far outweigh the risks Disclosure R.E.J. Ryder: None. J.P. Teare: None. A. Ruban: None. M. Haluzik: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Abbott Diabetes, AstraZeneca, Lilly Diabetes, Novartis AG. L. Munro: None. H. Frydenberg: None. J.J. McMaster: None. S. Fishman: None. R.V. Cohen: Advisory Panel; GI Dynamics. Research Support; Johnson & Johnson, Medtronic. C.M. Aboud: None. G.J. Holtmann: Research Support; AbbVie Inc., Allergan, Arena Pharmaceuticals, Inc., Bayer, Bristol Myers, Datapharm Australia Pty Ltd Commonwealth Laboratories, Pty Limited, Eli Lilly Australia Pty Limited, F.Hoffmann-La Roche Limited, Falk Foundation, Falk GmbH and Co Kg, GI Therapies Pty Ltd, Gilead Sciences Pty Limited, MedImmune Ltd Celgene Pty Limited, Mylan, Nestle Pty Ltd, Prometheus Laboratories, Quintiles Pty Limited, Servatus, Takeda Development Center Asia, Pty Ltd, Vital Food Processors Ltd. C. de Jonge: None. J. Greve: Advisory Panel; GI Dynamics. Other Relationship; Bariatric Solutions International, Ethicon, Inc. J.C. Mason: None. H. Sourij: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk. Research Support; Boehringer Ingelheim International GmbH, Sanofi. Speaker's Bureau; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk. R. Drummond: Research Support; Fractyl Health, Inc. Speaker's Bureau; AstraZeneca, Bristol-Myers Squibb Company. B. McGowan: Advisory Panel; Johnson & Johnson, Lilly, Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; AstraZeneca, Novo Nordisk. Stock/Shareholder; Reset Health. S.A. Amiel: Advisory Panel; Medtronic, Novo Nordisk. Other Relationship; Sanofi. M. Yadagiri: None. P. Sen Gupta: None. K. Laubner: None. J. Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH. Research Support; Boehringer Ingelheim International GmbH. Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. Funding Association of British Clinical Diabetologists

807-P: Glycemic Control in People with Type 2 Diabetes (PWT2D) Switching from NPH to Insulin Glargine 300 U/mL (Gla-300) : REALI Pooled Database

The effectiveness of Gla-300 in PWT2D switching from NPH is not widely documented. REALI database combines individual data from 14 European studies in T2D. We analyzed data from PWT2D uncontrolled on prior basal insulin (BI) , 1282 switching from NPH and 2899 from other non-NPH BIs (mainly glargine 100 U/mL, 67%) to Gla-300. In the NPH group, mean±SD age was 63±9.4 years, BMI 32.5±5.8 kg/m2, and median diabetes duration 12 years. The majority previously used biguanides (71%) , followed by sulfonylureas (20%) , and dipeptidyl peptidase 4 inhibitors (18%) . HbA1c markedly improved after a 24-week Gla-300 therapy (Figure 1A) . Mean±SD fasting plasma glucose (FPG) decreased from 188.8±55.9 mg/dL at Baseline to 143.3±45.5 at Week 24. Gla-300 was started at a mean dose of 29.4 U/day and titrated up to 35.6 at Week 24, with no body weight (BW) change. In the non-NPH BI group, baseline characteristics were comparable to those in the NPH group, except for higher baseline HbA1c and FPG in the latter. Figure 1B illustrates HbA1c improvement in the non-NPH BI group, at a mean Gla-300 starting dose of 35.4 U/day increasing to 41.7 at Week 24, with no BW change. Hypoglycemia was similarly low in both groups. This analysis shows that PWT2D, previously uncontrolled on BI, benefited from switching to Gla-300 in terms of HbA1c improvement, and this was especially observed in those previously treated with NPH. Disclosure D.Müller-wieland: Advisory Panel; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Amarin Corporation, Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. N.Freemantle: Consultant; Novo Nordisk, Research Support; Aimmune, ALK-Abelló A/S, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Sanofi, Vertex Pharmaceuticals Incorporated, Speaker's Bureau; Abbott. R.C.Bonadonna: Advisory Panel; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk. C.Mauquoi: None. G.Bigot: None. M.Bonnemaire: Employee; Sanofi. P.Gourdy: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mundipharma, Novo Nordisk, Sanofi, Sanofi, Speaker's Bureau; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk. D.Mauricio: Advisory Panel; Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Speaker's Bureau; Almirall, S.A., Esteve, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. Funding Sanofi

733-P: Initiation of iGlarLixi vs. Basal-Bolus Insulin (BB) in Adults with Type 2 Diabetes (T2D) Advancing from Basal Insulin (BI) Therapy: The SoliComplex Real-World Study

Aim: When T2D is suboptimally controlled with BI, 1-3 daily injections of prandial insulin are commonly added (BB regimen) . Once daily iGlarLixi is an alternative treatment. This analysis evaluated the use of iGlarLixi vs. BB on T2D outcomes. Methods: This retrospective analysis of the US Optum Clinformatics database compared outcomes in adults (≥18 y) with T2D who previously received BI and newly initiated iGlarLixi or BB between Jan 1, 2017, and Jun 30, 2020. Persistence (primary endpoint) , adherence, healthcare resource utilization (HRU) , costs, any hypoglycemia, and HbA1c change were assessed at 12 months. Results: Propensity score matching generated cohorts (n=1070 each) that were well balanced with similar mean ± SD age (iGlarLixi: 63.9 ± 11.0 y; BB: 64.5 ± 11.3 y) , HbA1c (iGlarLixi: 9.2 ± 1.7%; BB: 9.2 ± 1.8%) , oral agent use, BI use, and HRU. The primary endpoint was met with treatment persistence being statistically significantly higher for iGlarLixi vs. BB at 12 months. Adherence was numerically higher for iGlarLixi, and hypoglycemia rates, HRU and costs, numerically lower. HbA1c reduction was similar between groups (Table) . Conclusions: In this observational study, initiation of once daily iGlarLixi vs. BB insulin was associated with higher persistence and similar HbA1c reduction without increasing HRU or costs. Disclosure K.M. Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. C. Heller: Consultant; Sanofi. Employee; Aetion. R. Lajara: None. E. Lew: Employee; Sanofi. X. Li: Employee; Eisai Co., Ltd., Sanofi. T.A. Dex: Employee; Sanofi. Stock/Shareholder; Pfizer Inc., Teva Pharmaceutical Industries Ltd., Viatris Inc. R. Kilpatrick: Speaker's Bureau; Abbott Diabetes, Amgen Inc., Novo Nordisk, Sanofi. Funding Sanofi

1326-P: Baseline OGTT as a Predictor of Type 2 Diabetes Progression in the GRADE Study

Type 2 diabetes (T2D) is progressive, often requiring additional medications to maintain glycemic control. We assessed baseline β-cell function and insulin sensitivity as predictors of worsening glycemia (HbA1c) in the GRADE Study. Adults with T2D <y and HbA1c 6.8-8.5% were randomized to glimepiride, sitagliptin, insulin glargine 100 U/mL or liraglutide added to metformin monotherapy. Complete baseline OGTT data were available for 4586 of 5047 participants (Mean±SD: Age 57±y, 64% male, 5.0±1.3 y f/up) . Insulin sensitivity (HOMA2S) and early (C-peptide index (CPI) : ΔCP/ΔG 0-30 min) and total (incAUC-CP/G 0-120 min) C-peptide responses were used in Cox proportional hazard models to predict time to 1° (HbA1c ≥7%) and 2° (HbA1c >7.5%) glycemic outcomes and tested for treatment interaction. Given the inverse relationship with insulin sensitivity, C-peptide responses were adjusted for HOMA2S. Values determined at baseline (mean±SD) were: CPI 0.8±.nmol/g, incAUC CP/G 1.0±0.6 nmol/mg, HOMA2S 35±68 %, fasting glucose 152±31 mg/dl. Higher C-peptide responses predicted lower risk of 1° (CPI: HR±SE per 1 unit change =0.74±0.03, p<0.001; incAUC-CP/G: HR=0.68±0.02, p<0.001) and 2° glycemic outcomes (CPI: HR=0.71±0.03, p<0.001; incAUC-CP/G: HR=0.60±0.03, p<0.001) . Risks did not differ by treatment. There was interaction for HOMA2S and treatment; a 5 unit change in HOMA2S predicted lower risk of 1° and 2° outcomes with glimepiride and sitagliptin (HR=0.97±0.for both 1° outcomes; HR=0.96±0.for 2° outcome with glimepiride, HR=0.95±0.for 2° outcome with sitagliptin; all p<0.05) . A mg/dL change in fasting glucose predicted greater risk of 1° outcomes for all treatments, lowest for insulin glargine (HR=1.05±0.01) and highest for sitagliptin (HR=1.11±0.01) . Conclusions: Impaired β-cell function based on an OGTT predicted higher risk of T2D progression regardless of assigned treatment. This approach may identify cases that may benefit from earlier more aggressive therapy. Disclosure K.Utzschneider: Consultant; Nevro Corp. T.A.Elasy: None. W.Valencia: None. C.Ma: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. S.E.Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc. W.Sivitz: n/a. Grade research group: n/a. N.Younes: None. N.M.Butera: None. A.Balasubramanyam: None. C.Desouza: Advisory Panel; AstraZeneca, Bayer AG, Novo Nordisk A/S, Consultant; Asahi Kasei Corporation. J.Krakoff: None. J.I.Barzilay: None. R.A.Defronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Speaker’s Bureau; AstraZeneca. R.M.Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246, U34-DK-088043)

1102-P: Identifying Blood Biomarkers for Type 2 Diabetes Subtyping: A Report from the ORIGIN Trial

Diabetes (DM) can be classified into 5 subtypes characterized by distinct progression in dysglycaemia and complications. Using 5 clinical variables, we categorized 7017 participants from the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial into 1/auto-immune DM (n=241) , 2/insulin-deficient DM (n=1594) , 3/insulin-resistant DM (n=914) , 4/obesity-related DM (n=1595) , 5/age-related DM (n=2673) .Yet, whether blood biomarkers are associated with these subtypes is unknown. Forward-selection logistic regression models were used to identify biomarkers that were each independent determinant of one cluster versus the others, among 233 selected cardiometabolic proteins measured at baseline. Models were adjusted for age, sex, ethnicity, C-peptide level, diabetes duration. A total of 13, 2, 7 and biomarkers were independent determinants of DM subtypes 2 to 5 respectively (all P<4.3x10-5) . A combination of 5 biomarkers that were distinctively associated with clusters (fig) , showed a diagnosis performance, through AUC-ROC curves, of 0.71, 0.86, 0.88, 0.82 to respectively distinguish cluster 2 to 5 from the others. No biomarkers other than GAD antibodies were determinants of cluster 1. We identified 5 serum biomarkers, as independent determinants of DM subtypes, that could be used as a diagnosis test for DM subtyping. Although this requires further validation in an independent population. Disclosure M.Pigeyre: n/a. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. L.Groop: None. S.Hess: Employee; Sanofi. G.Pare: Advisory Panel; Amgen Inc., Bayer AG, Sanofi, Research Support; Bayer AG. Funding NCT00069784 Canadian Institute of Health Research Sanofi

106-OR: Fetal Sex Influences Maternal Insulin and Glucose Metabolism in Pregnancy

Aims and Hypothesis: Women carrying a male fetus are suggested to have altered maternal glucose and insulin dynamics and increased rates of GDM, but current literature remains inconclusive. We aimed to determine the relationship between fetal sex and maternal glucose and insulin metabolism and assess whether inclusion of fetal sex improves prediction of IADPSG GDM. Methods: Using blinded data from five Hyperglycaemia and Adverse Pregnancy Outcome study centres, we examined maternal metabolic data at mean gestational week 28 in 6337 untreated women. Stratifying women by either male (n = 3273) or female fetus (n = 3064) we analysed data from the 75g OGTT, estimates of insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral Disposition index) using multiple linear regression analysis. To assess the relationship and predictive ability of fetal sex and GDM we utilised multiple logistic regression and receiver operating characteristic curve analysis. Results: Women carrying a male fetus were found to have a modest increase in fasting plasma glucose (4.52 vs. 4.44 mmol/L; P=0.008) and 1 h glucose (7.57 vs. 7.46 mmol/L; P=0.015) during OGTT which translated into an overall increase in the OGTT z score (0.vs. 0.02; P=0.005) . The Matsuda (β: -0.06; 95% CI [-0.10, -0.02]; P=0.008) and oral Disposition index (β: -0.07; 95% CI [-0.11, -0.02]; P=0.005) were significantly reduced in women carrying a male fetus after correction for established maternal clinical risk factors. Women carrying a male fetus were not at higher odds of developing GDM in adjusted (aOR: 1.04; 95% CI [0.9, 1.19]; P=0.6) or unadjusted (OR: 1.09; 95% CI [0.96, 1.25]; P=0.16) models. Conclusion/interpretation: The male fetus is associated with increased maternal fasting and postprandial glucose with concomitant decreased insulin sensitivity and β-cell compensation. The alterations in maternal glucose and insulin dynamics associated with having a male fetus does not translate into a clinical diagnosis of GDM. Disclosure T.P.Mullins: None. K.S.Gibbons: None. L.R.Madsen: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. W.H.Tam: None. P.Catalano: None. D.A.Sacks: None. H.L.Barrett: None. D.Mcintyre: None.

925-P: European Survey on Adults with Type 1 Diabetes (T1D) and Their Caregivers: Insights into Experience of T1D Management

Background and Aims: T1D requires constant self-management and can substantially impact quality of life. We aimed to survey patient and caregiver experiences of T1D management. Methods: Adult people with T1D (PwD) or their caregivers living in France, Germany, Italy, Spain, or the UK were invited to complete an online survey (July-August 2021) . Results: Responders were 458 PwD (54% female, mean age 47.8 years, mean age at diagnosis 24.4 years) and 54 caregivers. For PwD, moderate to very high impacts of T1D on daily life included fatigue (77%) and anxiety (65%) . The top 2 other illnesses with significant impact on PwD’s lives were hypertension (29%) and depression (26%) . Many PwD (68%) would have liked more psychological support, mainly from healthcare professionals (HCPs) . Most caregivers (76%) would have liked support, mainly from HCPs, especially diabetologists (39%) , nutritionists (31%) and psychologists (28%) . Over half of responders felt they lack knowledge on T1D (53% PwD, 56% caregivers) . Only 57% of PwD and 39% of caregivers had participated in education programmes; of those <30% of PwD/caregivers still regularly attended. There were regional differences in the proportion of PwD who had attended education programmes (Figure) , but not in the proportion who still were regularly attending. Conclusion: In Europe, PwD and their caregivers require more support and education for T1D management. Disclosure B.Kulzer: Advisory Panel; Bayer AG, Bayer AG, Becton, Dickinson and Company, Becton, Dickinson and Company, Berlin-Chemie AG, Berlin-Chemie AG, Dexcom, Inc., Dexcom, Inc., Insulet Corporation, Novo Nordisk, Roche Diabetes Care, Sanofi, Sanofi-Aventis Deutschland GmbH, Research Support; Novo Nordisk, Roche Diabetes Care. S.Down: Advisory Panel; Viatris, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, Viatris. A.Seignez: Employee; Else Care. A.Vives: Other Relationship; Sanofi. M.Bonnemaire: Employee; Sanofi. A.Penfornis: Board Member; Insulet Corporation, Medtronic, Mundipharma, Novo Nordisk, Sanofi, Speaker's Bureau; Glooko, Inc., Insulet Corporation, Lilly, Novo Nordisk, Ypsomed AG. Funding Sanofi

626-P: TheraKey Diabetes 3.0 App: Better Self-Management, Well-Being, Adherence, and Less Diabetes Distress of People with Diabetes

Aim: The TheraKey Diabetes 3.0 app supports people with diabetes (PwD) during diabetes diagnosis and in the further course of the disease by providing personalized content (e.g., information, graphics, educational videos, testimonials, worksheets, interactive elements) , knowledge and skills for better self-management and coping with the diabetes disease or therapy in everyday life. This study examined the effect in terms of patient-reported outcomes. Methods: Online survey of users of MyTherakey Diabetes 3.0 with a pre-post design at 4 (t1) and 12 weeks (t2) . 185 PwD (15,1% type 1 diabetes (T1D) , 79.5% type 2 diabetes (T2D) , 43,2% female, average age 53.5 years, diabetes duration 3,6 (± 7,2) years, BMI 32,3 (± 7,8) kg/m², 34,6% insulin therapy, HbA1c 8,3 ± 2,5%) . Response rate at t2: 55% (n=105) . Diabetes Self-Management: Diabetes Self-Management Questionnaire (DSMQ) , Problem Areas in Diabetes Scale (PAID-5) . Well-being: WHO-5. Active Patient Participation: Patient Activation Measure (PAM-13D) . Self-efficacy expectancy: General Self-efficacy Scale (GSE) . Health literacy: European Health Literacy Survey (HLS-EU-Q16) . Adherence: MARS D. Results: (t2) : DSMQ: 10,5 ± 10,8/13,3 ± 9,5, p<.0 (t1 p<.001) . WHO-5: 10,5 ± 4,4/11,7 ± 4,1, p=.0 (t1 p= .006) . PAID-5: 33,4 ± 22,5/29,6 ± 21,5, p=.015 (t1 p=.181) . MARS-D: 6,3 ± 1,7/6,8 ± 2,5, p=.022 (t1 p=.432) . PAM-13D: 42,7 ± 4,8/43,4 ± 5,1, p=.136 (t1 p=.426) . GSE: 21,4 ± 5,1/21,8 ± 5,0, p=.297 (t1 p=.167) . HLS-EU-Q16: 13,8 ± 7,4/12,4 ± 8,1, p=.036 (t1 p=.793) . Subgroup analyses show that PwD with short (< 1 year) and long duration of diabetes (< 5 years) and PwD-T2D benefit most. Conclusion: After 3 months of using the diabetes app, patient-relevant benefits can be observed in terms of improved self-management, better well-being, reduced diabetes-related burden, and better adherence. It remains unclear why health literacy is declining. The TheraKey 3.0 can positively support PwD in managing their diabetes. Disclosure B.Kulzer: Advisory Panel; Bayer AG, Bayer AG, Becton, Dickinson and Company, Becton, Dickinson and Company, Berlin-Chemie AG, Berlin-Chemie AG, Dexcom, Inc., Dexcom, Inc., Insulet Corporation, Novo Nordisk, Roche Diabetes Care, Sanofi, Sanofi-Aventis Deutschland GmbH, Research Support; Novo Nordisk, Roche Diabetes Care. D.Ehrmann: Advisory Panel; Dexcom, Inc., Consultant; mySugr, Roche Diabetes Care, Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc. T.Roos: None. N.Hermanns: Advisory Panel; Abbott Diabetes, Research Support; Becton, Dickinson and Company, Roche Diagnostics, Speaker's Bureau; Berlin-Chemie AG, Novo Nordisk, Sanofi.

732-P: Patients with Type 2 Diabetes Reach Glycemic Targets Faster with Tirzepatide Compared with Semaglutide and Titrated Insulin Degludec

Tirzepatide (TZP) is a novel dual GIP/GLP-1 receptor agonist in development for treatment of type 2 diabetes (T2D) . TZP 5 mg, mg, and 15 mg demonstrated superiority versus semaglutide 1 mg (SEMA) and titrated insulin degludec (iDeg) in HbA1c change from baseline and proportion of patients reaching HbA1c <7%, ≤6.5%, and <5.7% at 40-weeks (SURPASS-2) and 52-weeks (SURPASS-3) , respectively. In an exploratory pre-planned analysis, time to achieve glycemic targets was compared between treatments using cox proportional-hazards model. TZP was significantly faster than SEMA and iDeg in time to reach HbA1c <7%, ≤6.5% and <5.7% (Figure) . Median time to achieve HbA1c <7% was 8.1 weeks for all TZP doses versus 12.0 weeks for SEMA, and to reach ≤6.5% was 12.1 weeks versus 15.7 weeks, respectively. Additionally, TZP was significantly faster than SEMA in time to lose 5% and 10% body weight (Figure) . Consistently, median time to reach HbA1c <7% was 8.1 weeks for all TZP doses versus 12.1 weeks for iDeg, and to reach ≤6.5% was 12.1 weeks versus 24.1 weeks, respectively. Mild to moderate gastrointestinal adverse events were associated with TZP and primarily occurred during the dose escalation period. In conclusion, patients with T2D reached glycemic targets faster with TZP compared to SEMA 1 mg and titrated iDeg. Disclosure K.M. Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. A. Viljoen: Advisory Panel; Eli Lilly and Company, Mundipharma. Consultant; Amgen Inc., Daiichi Sankyo. Research Support; Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk A/S, Sanofi. R.J. Galindo: Advisory Panel; Sanofi, WW International, Inc. Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. X. Cui: Employee; Eli Lilly and Company. R. Huh: None. L. Fernandez Lando: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Patel: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

100-LB: Glycemic Control Using Recommended Settings in Youth and Adults with Type 1 Diabetes (T1D) —Minimed 780G System with the Calibration-Free Guardian 4 Sensor Results

Background: Safety and effectiveness outcomes of individuals using the MiniMed™ 780G system with the no-calibration Guardian™ 4 sensor during the first three months of use were analyzed. Methods: Participants (N=176, aged 7-75 years) with T1D used the Conformitè Europëenne-marked MiniMed™ 780G system. Safety and effectiveness endpoints (mean A1C, sensor glucose [SG], percentage of time spent at SG ranges and glucose variability) were collected over three months and summarized. Endpoints were also assessed when recommended settings (target of 100mg/dL and active insulin time of 2-3 hours) were used. Results: There was no DKA or severe hypoglycemia. At 3 months, A1C was 7.1% (N=164) , 7.2% (N=101) and 6.8% (N=63) for overall, pediatric and adult participants, respectively. Additional glycemic metrics are shown (Table) . With recommended settings, time spent in target range (TIR, 70-180 mg/dL) was 74.7% (N=119) , 72.7% (N=65) and 77.0% (N=54) , respectively, and time spent below range (TBR<70mg/dL) was 2.1%, 2.4% and 1.7%, respectively. Conclusion: This analysis demonstrates that individuals safely exceeded international consensus-recommended TIR and TBR goals when using the MiniMed™ 780G system with the Guardian™ 4 sensor. These results mirror those of the pivotal trial during use of the calibration-requiring Guardian™ sensor 3. Disclosure R. A. Vigersky: Employee; Medtronic. C. Pihoker: None. R. Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. J. Reed: None. J. Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker’s Bureau; Lilly Diabetes. D. I. Shulman: Advisory Panel; Medtronic. R. H. Slover: None. J. Thrasher: Advisory Panel; Eli Lilly and Company, Medtronic, Board Member; Medtronic, Consultant; Eli Lilly and Company, Medtronic, Research Support; Eli Lilly and Company, Medtronic, Novo Nordisk, Speaker’s Bureau; Bayer AG, Eli Lilly and Company, Medtronic, Sanofi. X. Chen: Employee; Medtronic, Medtronic. M. Liu: None. T. L. Cordero: Employee; Medtronic, Medtronic. B. W. Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker’s Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. M. Vella: Employee; Medtronic. A. S. Rhinehart: Employee; Medtronic, Stock/Shareholder; Medtronic. J. Shin: Employee; Medtronic. R. L. Brazg: Research Support; Abbott Diabetes, Lilly Diabetes, Medtronic, Novo Nordisk, Roche Diagnostics, Senseonics. B. A. Buckingham: Advisory Panel; Arecor, Lilly Diabetes, Medtronic, Other Relationship; Insulet Corporation, Research Support; Insulet Corporation, Lilly Diabetes, Medtronic. A. L. Carlson: Advisory Panel; MannKind Corporation, Employee; Bright Health Group, Other Relationship; Medtronic, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, UnitedHealth Group. K. B. Kaiserman: Advisory Panel; Medtronic, Consultant; Medtronic, Employee; MannKind Corporation, Research Support; Medtronic, Speaker’s Bureau; Medtronic, Stock/Shareholder; MannKind Corporation. M. Kipnes: None. D. R. Liljenquist: None. A. Philis-tsimikas: Advisory Panel; Bayer AG, Novo Nordisk, Research Support; Lilly Diabetes, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Viking Therapeutics.

190-LB: Vaspin—A Novel Predictor of Type 2 Diabetes Risk

Vaspin (visceral adipose tissue-derived serpinA12) is an adipokine suspected to be involved in type 2 diabetes (T2D) pathogenesis, linking obesity and T2D. We sought to assess epidemiological and genetic associations of vaspin with T2D and related variables. We assessed the relationship of body-mass index (BMI) and waist-hip ratio (WHR) and plasma vaspin concentration, along with the relationship between plasma vaspin and adiposity-related variables and T2D in (i) a case-cohort within the Prospective Urban and Rural Epidemiology (PURE) prospective multi-country study (N=10,052) , and (ii) the Outcome Reduction with Initial Glargine Intervention (ORIGIN) Trial (N=7,840) of participants with dysglycemia. We next investigated the predictive value of vaspin for T2D risk. All models adjusted for age, sex, and ethnicity. Using two-sample Mendelian randomization (MR) , we analyzed if genetically higher vaspin is causal for T2D. The MR analysis used 34 independent genetic variants (linkage disequilibrium r2<0.1) associated with vaspin concentration in PURE (N=3,513) , estimating their effect on BMI-adjusted T2D risk in the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis) consortium (N=898,130) . In PURE, a 1 unit increase in BMI and WHR was associated with a 0.01 SD (95% CI 0.01 - 0.02; P = 2.04x10−15) and 0.45 SD (95% CI, 0.21 - 0.70; P = 2.87 × 10−4) increase in plasma vaspin respectively. A 1 SD increase in plasma vaspin was associated with higher triglycerides (0.09 mmol/L; 95% CI, 0.07 - 0.12, P = 4.08x10−13) . Directionally-consistent associations were observed in ORIGIN. A 1 SD increase in plasma vaspin was associated with a 19% increase in incident T2D risk in PURE (HR, 1.19; 95% CI, 1.12 - 1.26; P = 6.36x10−8) and a 16% increase in prevalent T2D in ORIGIN (OR, 1.16; 95% CI, 1.07 - 1.25; P = 2.17x10−4) . Sensitivity analyses showed vaspin's specificity for T2D. Genetically-higher vaspin was associated with increased BMI-adjusted T2D risk (OR, 1.02; 95% CI, 1.00 - 1.03; P = 5.46x10−3) . Our data suggests that vaspin is a predictor for T2D risk, a modest causal factor for T2D development, and might represent a potential T2D therapeutic target. Disclosure H. Wang: None. M. Chong: None. N. Perrot: None. J. Feiner: None. S. Hess: Employee; Sanofi. S. Yusuf: None. H. C. Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. G. Pare: Advisory Panel; Amgen Inc., Bayer AG, Sanofi, Research Support; Bayer AG. M. Pigeyre: n/a. Funding PURE biomarker study was sponsored by Bayer and CIHR. Origin (NCT00069784) and the biomarker-substudy in Origin were sponsored by Sanofi and CIHR.

739-P: iGlarLixi vs. Premixed Insulin Initiation in Adults with Type 2 Diabetes (T2D) Advancing from Basal Insulin (BI) Therapy: SoliComplex Real-World Study

Aim: Premixed insulin (premix) , conventionally administered twice daily, is often used in the US to treat T2D that is suboptimally controlled with BI, particularly for people with consistent eating patterns who require affordable treatment. This analysis evaluated use of once daily iGlarLixi vs. premix on T2D outcomes. Method: This retrospective analysis of the US Optum Clinformatics database compared outcomes in adults (≥18 y) with T2D who previously received BI and newly initiated iGlarLixi or premix. Persistence (primary endpoint) , adherence, healthcare resource utilization (HRU) , costs, any hypoglycemia, and HbA1c change were assessed at 12 months. Results: After propensity score matching, cohorts (n=834 each) were well balanced with respect to age, HbA1c, use of oral agents, BI, and HRU. The primary endpoint was met with persistence being statistically significantly higher for iGlarLixi vs. premix at 12 months. Adherence and HbA1c reduction were similar between groups, whereas hypoglycemia rates, HRU, and costs were numerically lower for iGlarLixi (Table) . Conclusion: In this observational study, once daily iGlarLixi was an effective post-BI treatment with higher treatment persistence than premixed insulin, with similar adherence and HbA1c reduction, and numerically lower hypoglycemia rates, HRU, and costs. Disclosure R.Lajara: None. C.Heller: Consultant; Sanofi, Employee; Aetion. K.M.Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. E.Lew: Employee; Sanofi. X.Li: Employee; Eisai Co., Ltd., Sanofi. T.A.Dex: Employee; Sanofi, Stock/Shareholder; Pfizer Inc., Teva Pharmaceutical Industries Ltd., Viatris Inc. R.Kilpatrick: Speaker's Bureau; Abbott Diabetes, Amgen Inc., Novo Nordisk, Sanofi. Funding Sanofi

1495-PUB: Insulin Patch Pumps: Are There Patient-Related Advantages for People with Diabetes?

Objective: Patch pumps, i.e. tubeless insulin pumps, are an attractive alternative to conventional insulin pumps for people with type 1 diabetes and type 2 diabetes on insulin therapy. However, to date, the patient-related benefits of patch pumps are not well understood. Methods: A systematic review was conducted to summarize potential patient-relevant advantages and disadvantages of patch pumps and to assess relevant studies on patient-reported outcomes (PROs) . Relevant studies were identified by a systematic PubMed search. In addition, the reference lists of the respective articles and Google Scholar were checked for further references. English-language articles published before June 30, 2021, were included; no other publication date criteria were specified. Results: A total of 12 studies were included. The results of this analysis demonstrate that patch pumps improve quality of life, reduce diabetes-related symptoms, increase patient satisfaction, and are preferred by patients compared with conventional insulin pumps and daily multiple injection (MDI) therapy. However, several methodological limitations of the identified studies limit the power of this analysis. Conclusions: Despite the limited number of studies evaluating the benefits of patch pumps in relation to PROs, there is increasing evidence that people with diabetes prefer patch pumps compared to MDI and conventional pumps. It is notable that this aspect has been relatively understudied. More systematic studies evaluating the benefit of patch pumps in relation to PROs are needed. Disclosure B.Kulzer: Advisory Panel; Bayer AG, Bayer AG, Becton, Dickinson and Company, Becton, Dickinson and Company, Berlin-Chemie AG, Berlin-Chemie AG, Dexcom, Inc., Dexcom, Inc., Insulet Corporation, Novo Nordisk, Roche Diabetes Care, Sanofi, Sanofi-Aventis Deutschland GmbH, Research Support; Novo Nordisk, Roche Diabetes Care. G.Freckmann: Advisory Panel; Abbott Diabetes, Dexcom, Inc., Lilly, Roche Diabetes Care, Roche Diagnostics, Consultant; Ascensia Diabetes Care, Berlin-Chemie AG, Boydsens, Metronom, mySugr, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Research Support; Dexcom, Inc., Medtronic, Menarini Group, Roche Diabetes Care, Sanofi, Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc., Lilly, Novo Nordisk, Roche Diabetes Care, Terumo Corporation. L.Heinemann: Board Member; Lifecare, Inc., Consultant; Becton, Dickinson and Company, Roche Diabetes Care, Stock/Shareholder; Profil Institut für Stoffwechselforschung GmbH, Science Consulting in Diabetes GmbH. O.Schnell: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Roche Diabetes Care. R.Hinzmann: Employee; Roche Diabetes Care. R.Ziegler: Advisory Panel; Eli Lilly and Company, mySugr, Novo Nordisk, Roche Diabetes Care, Speaker's Bureau; A. Menarini Diagnostics, Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Glooko, Inc., Novo Nordisk, Roche Diabetes Care.

796-P: Perceived Potential Benefits and Barriers for Using a Bionic Invisible Pancreas

A fully implantable automated insulin delivery system consisting of an intraperitoneal pump and an implantable CGM sensor (Bionic Invisible Pancreas - BIP) is under development. The occurrence of potential benefits or barriers to the use of the BIP was assessed in people with diabetes under different treatment regimens (MDI, CSII, CSII and CGM) . They were asked to provide a rating of 9 potential benefits and potential barriers of BIP on a five-point Likert scale ranging from 1 - strongly disagree - to 5 - strongly agree. Data from 38 people with type 1 diabetes were analysed (MDI: n=12; CSII: n=14; CSII and CGM: n=12) . In general, participants reported more expected benefits than barriers. The main benefits were increased flexibility and better glucose levels. The main expected barriers related to problems in transferring control to BIP and fears about side effects of implantation (e.g. inflammation) . The benefits and barriers were similar in all three groups (p=0.861 and p=0.669 for differences between groups, respectively) . 76.3% of participants reported that they would use BIP. Participants reported more positive than negative expectations related to the BIP device, regardless of previous insulin treatment. In addition to the fear of side effects during implantation, giving control to the BIP device was perceived as challenging. The present work was supported by H2020-FETPROACT Project FORGETDIABETS, n. 951933 Disclosure N.Hermanns: Advisory Panel; Abbott Diabetes, Research Support; Becton, Dickinson and Company, Roche Diagnostics, Speaker's Bureau; Berlin-Chemie AG, Novo Nordisk, Sanofi. K.Finke-groene: Speaker's Bureau; Berlin-Chemie AG. B.Kulzer: Advisory Panel; Bayer AG, Bayer AG, Becton, Dickinson and Company, Becton, Dickinson and Company, Berlin-Chemie AG, Berlin-Chemie AG, Dexcom, Inc., Dexcom, Inc., Insulet Corporation, Novo Nordisk, Roche Diabetes Care, Sanofi, Sanofi-Aventis Deutschland GmbH, Research Support; Novo Nordisk, Roche Diabetes Care. D.Ehrmann: Advisory Panel; Dexcom, Inc., Consultant; mySugr, Roche Diabetes Care, Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc. Funding The present work was supported by H2020-FETPROACT Project FORGETDIABETS, n. 951933

1276-P: Transancestral Genomic Analysis Links Dysregulation of Valine Metabolism to the Development of Heart Failure in Type 2 Diabetes

Persons with type 2 diabetes (T2D) remain at increased risk of heart failure (HF) despite control of known cardiovascular risk factors. The aim of this study was to identify genes and molecular pathways specifically linking T2D to HF. To this end, we conducted a trans-ancestral genome-wide association study (GWAS) using data from ACCORD, ORIGIN, and six TOPMed cohorts (ARIC, CHS, FHS, JHS, MESA, WHI) . Included were a total of 19,8 participants with T2D (11,852 Whites, 4,152 Blacks, 3,157 Hispanics, and 778 Asians) , 1,8 of whom had developed HF, as defined in each study, after being diagnosed with T2D. A novel genome-wide significant trans-ancestral locus was identified on chromosome 7q21 as being associated with HF (lead SNP=rs6462012, OR=1.25[1.15-1.35], p=3.3 × 10-8) . The lead SNP had similar effect in all ethnicities (Whites: OR=1.28[1.16-1.42], p=9.0 × 10-7; Blacks: OR=1.24[1.06-1.42], p=5.0 × 10-3; Asians: OR=2.38[0.66-12.95], p=0.20) , except Hispanics (OR=1.00[0.80-1.26], p=0.98) . This HF locus appeared to be specific to T2D as it was not found among non-diabetic subjects from the six TOPMed cohorts (OR=1.01[0.95-1.08], p=0.71) or in previous GWAS from the general population. Among subjects with T2D included in the GTEx database, the risk allele at this locus was associated with decreased myocardial expression (beta=-0.19, SE=0.07, p=0.02) of the nearby HIBADH gene coding for the enzyme converting 3-hydroxyisobutyrate (a valine metabolite) to methylmalonic acid semialdehyde, while there was no such association among non-diabetic subjects (beta=0.009, SE=0.03, p=0.77) . In conclusion, we have identified a new HF locus specific for T2D that is linked to branched chain amino acid metabolism, the dysregulation of which has been previously implicated in the development of HF. Further investigation of the mechanisms linking this locus to HF may foster new HF-preventing interventions specifically targeted to the T2D population. Disclosure Y.Tang: None. J.I.Rotter: None. S.S.Rich: None. J.B.Meigs: Consultant; Quest Diagnostics. A.Manning: None. J.Mychaleckyj: None. A.Doria: Research Support; Novo Nordisk Foundation. C.Nlbi trans-omics for precision medicine (topmed) : n/a. M.Pigeyre: n/a. X.Sun: n/a. M.Morieri: Advisory Panel; Merck Sharp & Dohme Corp., Consultant; neopharmed gentili, SLAPharma, Other Relationship; Lilly, Novo Nordisk, Servier Laboratories. H.Shah: None. G.Pare: Advisory Panel; Amgen Inc., Bayer AG, Sanofi, Research Support; Bayer AG. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. K.Taylor: None. V.S.Ramachandran: None. Funding NIH Biodata Catalyst Fellowship (1OT3HL142479-01, 1OT3HL142478-01, 1OT3HL142481-01, 1OT3HL142480-01, 1OT3HL147154) .

268-OR: Impact of the COVID-Pandemic on Antihyperglycemic Prescription Patterns in Canada

Background: COVID-public health measures may have impacted diabetes care through delayed care and reduced medication access. This study describes antihyperglycemic medication prescription patterns among adults with type 2 diabetes (T2D) before and during the COVID-pandemic in Canada. Methods: Using IQVIA’s longitudinal pharmacy based prescription data, antihyperglycemic prescriptions from March 1, 2018 to February 28, 2021 were analyzed among adults who had ≥1 prescription for a non-insulin antihyperglycemic drug. The number of people who: 1) had antihyperglycemic prescriptions,2) were newly started on antihyperglycemic drugs, and3) were newly diagnosed with T2D (inferred from prescriptions) were reported. Results: The number of people who had ≥1 antihyperglycemic prescription was comparable in the year of the COVID-pandemic (March 2020 to February 2021) and the year prior (March 20to February 2020) . The number of people who newly initiated a GLP-1RA, SGLT2i or second-generation basal insulin analogue decreased for the first few months of the pandemic (April to September 2020) with recovery thereafter. The number of people who were newly diagnosed with T2D decreased by 7% in the COVID-year. Conclusion: Fewer people initiated newer antihyperglycemic medications and fewer people were newly diagnosed with T2D in the first few months for the pandemic which may reflect reduced health care access. Disclosure A.Y.Cheng: Advisory Panel; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, HLS Theraoeutics, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Sanofi, Board Member; Type 1 Diabetes Think Tank Network, Other Relationship; Diabetes Canada, Speaker's Bureau; Bausch Health, Canada, Merck & Co., Inc. R.Goldenberg: Consultant; IQVIA Inc., Speaker's Bureau; Amgen Canada, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi. I.E.Krawchenko: Speaker's Bureau; Janssen Pharmaceuticals, Inc. R.Tytus: Other Relationship; Banty , Boehringer Ingelheim International GmbH, Canadian Health Research Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc. J.Hahn: Employee; Novo Nordisk Canada Inc. A.R.Liu: Employee; Novo Nordisk A/S, Novo Nordisk Canada Inc. T.Lan: Other Relationship; Novo Nordisk Canada Inc. B.Millson: Other Relationship; Novo Nordisk Canada Inc. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation.

1191-P: Predictors of Hemoglobin A1c Testing in Adults with Type 2 Diabetes Covered by Alabama Medicaid

Background: ADA Standards of Care recommend A1C tests at least twice per year for patients with diabetes. We evaluated predictors of A1C testing among adults with type 2 diabetes covered by Alabama Medicaid. Methods: We conducted a retrospective analysis of Medicaid claims data between 2011-2020 using person-year observations as the unit of analysis. Inclusion criteria were ages 19-64 years, type 2 diabetes diagnosis, continuous Medicaid enrollment for the full calendar year and the year prior. The primary outcomes were receiving ≥1 and ≥2 A1C test (s) during a calendar year. We conducted multivariable Poisson regression stratified by eligibility (i.e. disability, poverty) to evaluate the relationships of study year, demographics, clinical factors, and healthcare utilization with A1C tests using generalized estimating equations to account for individuals contributing >1 observations. Results: We analyzed 288,379 person-year observations; 69% were female; 49% were Black; 47% were 35-54 years old, 44% 55-64 years old; 51% were eligible based on disability, 49% based on poverty. Overall, 57% observations had ≥1 A1C test per year, 35% had ≥2 A1C tests. More observations eligible by disability had ≥1 A1C test (76% vs. 38%) and ≥2 A1C tests (49% vs. 20%) than those eligible by poverty. For observations eligible by disability, Black race and older age were associated with higher likelihood of having ≥1 A1C test. For observations eligible by poverty, year after 2011, female sex, and younger age were associated with higher likelihood of having ≥1 A1C test. For both groups, rurality, insulin use, endocrinology care, diabetes complications, and ambulatory care visits were associated with higher likelihood of having ≥1 A1C test. Conclusions: Just over one-third of adults with diabetes covered by Alabama Medicaid had at least 2 A1C tests per year. A1C testing frequency differed by Medicaid eligibility; poverty-based eligibility was associated with lower likelihood of having recommended A1C testing. Disclosure C.A.Presley: None. C.R.Howell: None. Y.Khodneva: None. K.R.Riggs: n/a. L.Huang: None. E.B.Levitan: Research Support; Amgen Inc. A.Cherrington: Consultant; Bayer AG, Other Relationship; Novo Nordisk. Funding National Institute of Diabetes and Digestive and Kidney Diseases R18DK109501PI: CherringtonUAB Diabetes Research Center P30 DK079626PI: Cherrington

30-OR: Effects of Vitamin D Supplementation by Race and Weight Status on Serum Vitamin D Measures and Diabetes Risk in the D2d Study

Higher blood 25 (OH) D is associated with lower risk of type 2 diabetes (T2D) in people with prediabetes. Blood 25 (OH) D can vary due to skin color and weight. It is not known if blood 25 (OH) D levels have similar impact on T2D risk for people of color or higher weight. The vitamin D and type 2 diabetes (D2d) study is a randomized clinical trial of participants with high-risk prediabetes and overweight/obesity who were randomized to vitamin D3 4000 IU daily vs. placebo and followed for 2.5 years for the primary outcome of T2D. We compared baseline and intra-trial (mean achieved) serum 25 (OH) D among race-weight groups. We used Cox models to determine the associations between intra-trial serum 25 (OH) D and T2D risk by race-weight groups; we additionally tested for interactions between intra-trial serum 25 (OH) D and race or weight. Of 2362 D2d participants with self-reported race, Black (n = 616) and White (n = 1616) participants were included in analyses. Baseline serum 25 (OH) D was lower in Black (24.2 ng/mL ± 10.9) compared to White (29.6 ng/mL ± 9.5) participants (P<0.001) ; and were lower in those with higher vs. lower BMI in both races. Intra-trial serum 25 (OH) D was lower in Black participants (P<0.001) overall and those with higher baseline BMI. Both Black and White participants with intra-trial serum 25 (OH) D ≥ 40 ng/mL had significantly reduced risk of T2D [HR (95% CI) ]; Black: 0.51 (0.29, 0.92) ; White 0.42 (0.30, 0.60) ] with no significant race*BMI interaction. Participants with baseline BMI ≤ 40 kg/m2 who achieved intra-trial serum 25 (OH) D levels ≥ 40 ng/mL had significantly reduced risks of T2D but not those with a BMI > 40 kg/m2 with no significant BMI*race interaction. Conclusions: An intra-trial mean serum 25 (OH) D level ≥ 40 ng/mL was associated with significantly reduced risk of T2D in Black and White D2d participants, but only among those with BMI < 40 kg/m2. Targeting a serum 25 (OH) D level ≥ 40 ng/mL would optimize T2D prevention efforts among people with high-risk prediabetes. Disclosure R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. B.Dawson-hughes: None. D2d research group: n/a. C.A.Davenport: None. K.C.Johnson: None. S.Kashyap: Advisory Panel; Fractyl Health, Inc., GI Dynamics, Research Support; Janssen Pharmaceuticals, Inc. E.S.Leblanc: n/a. J.P.Nelson: None. E.Vickery: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. A.G.Pittas: None. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)