bluuebunny/crossref_metadata_2025 huggingface dataset:
718-P: Patients Achieving an HbA1c <5.7% with =5% Weight Loss and without Hypoglycemia: A Post Hoc Analysis of SURPASS 1 to 5
Authors: CHENG ALICE Y. , LINGVAY ILDIKO , CHOUDHARY PRATIK , GOMEZ-VALDERAS ELISA , ALLEN SHERYL , RANTA KARI T. , LEVINE JOSHUA A. , THIEU VIVIAN
Published: May 2022

In the phase 3 SURPASS studies of tirzepatide (TZP) , a novel dual GIP/GLP-1 receptor agonist developed for the treatment of type 2 diabetes, 23%-62% of TZP-treated participants achieved a HbA1c <5.7% and 54%-88% achieving ≥5% weight loss. This post hoc analysis evaluated the proportion of participants who achieved the triple endpoint of HbA1c <5.7%, ≥5% weight loss, and no clinically significant or severe hypoglycemia. We compared the proportion of participants achieving the triple endpoint between the TZP (5, 10, or 15 mg) and respective comparator groups using the efficacy analysis dataset without rescue medication. HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS 1, 2, 5) or week 52 (SURPASS 3, 4) . Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Significantly more participants treated with any dose of TZP achieved the triple endpoint compared to placebo or active comparators in SURPASS 1-5 (Figure) . Of the participants treated with TZP 15 mg, 45%, 48%, 48%, 41%, 55% reached the triple endpoint compared to 1% with placebo, 15% with semaglutide 1 mg, 2% with degludec, 1% with glargine U100, and 1% with placebo, in SURPASS 1-5, respectively. Significantly more participants treated with TZP achieved a HbA1c <5.7% with ≥5% weight loss and without hypoglycemia compared to placebo, semaglutide 1 mg, or basal insulin.

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. Speaker's Bureau; Bausch Health, Canada, Merck & Co., Inc. Other Relationship; Diabetes Canada. I. Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S. Consultant; Novo Nordisk. Research Support; NovoNordisk; Mylan; Merck, Sanofi. P. Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic. Research Support; Novo Nordisk. Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. E. Gomez-Valderas: Employee; Lilly. Stock/Shareholder; Lilly. S. Allen: None. K.T. Ranta: Employee; Eli Lilly and Company. J.A. Levine: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. V. Thieu: None.

Funding

Eli Lilly and Company
72-OR: Who Is Eligible and Gets Diabetes Screening in the U.S.?
Authors: ALI MOHAMMED K. , IMPERATORE GIUSEPPINA , BENOIT STEPHEN R. , HOLLIDAY CHRISTOPHER S. , O'BRIEN MATTHEW J. , TCHEUGUI JUSTIN B. ECHOUFFO , BULLARD KAI M.
Published: May 2022

To identify prediabetes/diabetes, the US Preventive Services Task Force (USPSTF) has recommended glucose testing in 40-70 year olds (2015) and now 35-70 year olds (2021) with overweight/obesity. Since 2002, the American Diabetes Association (ADA) has recommended prediabetes/diabetes screening based on a larger set of diabetes risk factors. We analyzed cross-sectional National Health and Nutrition Examination Survey data from 6,0non-pregnant US adults aged ≥18 years without diagnosed diabetes. For USPSTF 2015 and 2021, and ADA guidelines, we described which adults were eligible and ineligible for glucose testing, and proportions reporting receiving testing. We assessed sensitivity and specificity in identifying prediabetes (fasting plasma glucose [FPG] 100-125mg/dL or A1c 5.7-6.4% or both) or undiagnosed diabetes (FPG≥126mg/dL or A1c≥6.5% or both) . During 2013-2018, an estimated 76.7 million, 90.4 million, and 157.7 million US adults met eligibility for glucose testing by the USPSTF 2015, 2021, and ADA guidelines, respectively. Eligibility and proportions receiving testing varied by guideline (Figure 1) . Across definitions of prediabetes/diabetes, ADA recommendations were most sensitive (range: 91.0-99.1%) and least specific (24.1-35.3%) ; 2015 (sensitivity: 51.9-59.4%; specificity: 63.2-74.5%) and 2021 USPSTF (sensitivity: 57.5-66.6%; specificity: 56.6-67.1%) guideline sensitivity and specificity were comparable.

Disclosure

M.K.Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. G.Imperatore: None. S.R.Benoit: None. C.S.Holliday: None. M.J.O'brien: None. J.B.Echouffo tcheugui: None. K.M.Bullard: None.

Funding

MKA was partially supported by the Georgia Center for Diabetes Translation Research funded by the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024)
728-P: Glycemic Variability of Tirzepatide vs. Insulin Degludec in People with Type 2 Diabetes Using Continuous Glucose Monitoring (SURPASS-3 CGM)
Authors: BERGENSTAL RICHARD M. , BARTEE AMY , ZEYTINOGLU MELTEM , BRAY ROSS , ALLEN SHERYL , BROWN KATELYN
Published: May 2022

Tirzepatide (TZP) is a novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist in development for T2D. In a continuous glucose monitoring (CGM) sub-study of SURPASS-3 (NCT03882970) , participants with T2D on metformin with or without SGLT-2 inhibitors spent up to 91% of time in range (71-180 mg/dL) for TZP (5, 10, 15 mg) vs. 75% for insulin degludec (IDeg) (p<0.001) and within-day coefficient of variation was 16% vs. 24% for TZP vs. IDeg (p<0.001) . Reported here are additional pre-specified glycemic variability (GV) measures at 52 weeks for the sub-study (N=243; mean age of participants, 57 years; T2D duration, 8.8 years; baseline HbA1c, 8.14%) . The between-day GV measured as the mean of daily differences was significantly less for TZP vs. IDeg (TZP 5-15 mg; p<0.001) . The frequency and severity of hypoglycemic events measured by the low blood glucose (BG) index were significantly lower at all doses of TZP vs. IDeg (mg: p<0.05; 5, 15 mg: p<0.001) , as were hyperglycemic events measured by the high BG index compared to IDeg (5 mg: p<0.05; 10, 15 mg: p<0.001) . The BG risk index was significantly less at all doses of TZP (5 mg: p<0.05; 10, 15 mg: p<0.001) (Table) . TZP showed clinically meaningful and significant reductions in the risk of hyperglycemia and hypoglycemia in comparison to IDeg in people with T2D.

Disclosure

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. A.Bartee: None. M.Zeytinoglu: Employee; Eli Lilly and Company. R.Bray: Employee; Eli Lilly and Company. S.Allen: None. K.Brown: Employee; Eli Lilly and Company.
73-LB: Ambulatory Glucose Profile Informs Better Treatment Decisions for Type 2 Basal-Insulin Patients
Authors: HUANG EILEEN , NADA MOHAMED , WRIGHT EUGENE
Published: May 2022

Healthcare providers (HCP) treating patients who are on basal insulin and have suboptimal glycemic control may benefit from understanding glucose patterns. The primary objective of this study is to evaluate whether a review of Ambulatory Glucose Profile (AGP) of the patient would enable the HCP to recommend a therapy change. The secondary objectives included evaluating HCPs’ understanding of their patients’ glycemic control and patients’ understanding of the rationale for the recommended treatment after reviewing the AGP with their physician. A total of 136 patients with HbA1c values of 7.0 - 10.0% for whom their HCP is unsure of the optimal course of treatment based on standard of care were enrolled in the study at 10 sites and used FreeStyle Libre Pro Sensors;105 patients had at least 7 days of sensor data to generate an AGP. All HCPs received training on AGP interpretation. Based on their AGP, 94.3% (99/105) of the patients were recommended a therapy change. In addition, HCPs found that sensor data were useful in understanding their patients’ glycemic control, provided new insights on overall glucose control, and helped to make better informed treatment decisions for their patients (Table 1) . Patients also had a better understanding of the recommended treatment after reviewing the AGP with their HCP, where 96.7% of the patients understood the rationale of their recommended treatment.

Disclosure

E. Huang: Employee; Abbott Diabetes. M. Nada: Employee; Abbott Diabetes. E. Wright: Advisory Panel; Abbott Diabetes, Bayer AG, Boehringer Ingelheim International GmbH, Gelesis, GlaxoSmithKline plc., Lilly Diabetes, MannKind Corporation, Medtronic, Sanofi-Aventis U. S., Consultant; Abbott Diabetes, Bayer AG, Bigfoot Biomedical, Inc., Boehringer Ingelheim International GmbH, Lilly Diabetes, Stability Health, Other Relationship; UpToDate, Speaker's Bureau; Abbott Diabetes, American Diabetes Association, Bayer AG, Boehringer Ingelheim International GmbH, Sanofi-Aventis U. S.

Funding

Abbott Diabetes Care
732-P: Patients with Type 2 Diabetes Reach Glycemic Targets Faster with Tirzepatide Compared with Semaglutide and Titrated Insulin Degludec
Authors: PANTALONE KEVIN M. , VILJOEN ADIE , GALINDO RODOLFO J. , CUI XUEWEI , HUH RUTH , LANDO LAURA FERNANDEZ , PATEL HIREN
Published: May 2022

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
74-LB: Real-World Glycemic Outcomes in Adult Patients with Type 1 Diabetes Using a Real-Time Continuous Glucose Monitor Compared with an Intermittently Scanned Glucose Monitor and Self-Measured Blood Glucose—A Retrospective Observational Study from the Canadian
Authors: BROWN RUTH E. , CHU LISA , NORMAN GREGORY J. , ABITBOL ALEXANDER
Published: May 2022

Real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM) have both been shown to improve glycemic outcomes in people with T1D. In this retrospective analysis, we propensity score matched CGM naïve adults with T1D who initiated a rtCGM or an isCGM device. HbA1c and CGM metrics were assessed at 6-12-months.

Among the 143 matched patients/cohort (age 43 ± 14 years; T1D duration 22 ± 14 years; HbA1c 8.4 ± 1.0%) , rtCGM users had a significantly greater change in HbA1c (-0.7 ± 0.1%) compared to isCGM users (-0.4 ± 0.1%) (p=0.01) . There was a significantly greater change in HbA1c for rtCGM compared to isCGM when baseline HbA1c was <8.5% (difference -0.4% [-0.6 to -0.2], p<0.001) , and in MDI users (difference -0.3% [-0.5 to 0.0], p=0.04) . Compared to isCGM users, rtCGM users had significantly greater time in range (58.3 ± 16.1% vs. 54.5 ± 17.1%, p=0.03) , lower time below range (2.1 ± 2.7% vs. 6.1 ± 5.0%, p<0.001) and lower glycemic variability (Table) .

In this real-world analysis of adults with T1D, rtCGM users had a significantly greater reduction in HbA1c at 6-12 months, significantly greater time in range, lower time below range, and lower glycemic variability, compared to a matched cohort of isCGM users.

Disclosure

R. E. Brown: None. L. Chu: None. G. J. Norman: Employee; Dexcom, Inc. A. Abitbol: Consultant; Amgen Inc., AstraZeneca, Bayer Inc., Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Other Relationship; AstraZeneca, Bayer Inc., Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Novo Nordisk, Sanofi, Senseonics.

Funding

DexCom Canada, Co.
743-P: Effect of Once-Weekly TZP on Glycemic Control by Baseline Age in Patient Subpopulations from the SURPASS Trials
Authors: WYSHAM CAROL H. , TOFE SANTIAGO , SAPIN HELENE , MALIK RALEIGH , NEFF LISA M.
Published: May 2022

Tirzepatide (TZP) is a dual GIP and GLP-1 receptor agonist developed for the treatment of patients with type 2 diabetes (T2D) . The SURPASS clinical trials demonstrated efficacy and safety of TZP 5, 10, and 15 mg, administered once weekly in patients with T2D. This post-hoc analysis of the 5 SURPASS studies was undertaken to assess the efficacy of TZP in subgroups of subjects <65 years and ≥65 years of age. Prespecified subgroup analyses were conducted on the mITT population in all 5 global Phase 3 trials to assess the effects of treatment (TZP vs. placebo or active comparator) on change from baseline in HbA1c. End of treatment HbA1c was evaluated at week 40 or 52. Efficacy estimands, based on data collected from participants on treatment and without rescue medication, were utilized for all analyses reported here. For all 5 studies, analyses of change from baseline in HbA1c at 40 or 52 weeks for both age subgroups were consistent with the primary study results, with the treatment differences favoring all 3 doses of TZP compared with placebo (SURPASS-1 and -5) or active comparator (SURPASS-2, -3 and -4) (Figure) . The most frequent adverse events with TZP were mild-to-moderate, gastrointestinal-related and occurred during the dose-escalation period. In all 5 trials and for subjects in both prespecified age subgroups, TZP demonstrated significantly greater reductions in HbA1c versus placebo or active comparator.

Disclosure

C.H.Wysham: Research Support; Abbott, Corcept Therapeutics, Eli Lilly and Company, Mylan N.V., Novo Nordisk. S.Tofe: Advisory Panel; Lilly Diabetes, Novo Nordisk, Research Support; Lilly Diabetes, Novo Nordisk, Speaker's Bureau; Lilly Diabetes, Novo Nordisk. H.Sapin: Employee; Eli Lilly and Company. R.Malik: None. L.M.Neff: Employee; Eli Lilly and Company, Research Support; Amryt Pharma Plc, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company.
744-P: Effects of a Novel Long-Acting GIP/GLP-1/Glucagon Trireceptor Agonist, HISHS-3001, on HbA1c, Body Weight, and Lipid Metabolism
Authors: BURADE VINOD S. , GARCIA-OCANA ADOLFO , PRATLEY RICHARD E. , RUTTER GUY A. , VILSBØLL TINA , THORENS BERNARD , THENNATI RAJAMANNAR
Published: May 2022

HISHS-30is a novel long-acting, Gastric inhibitory peptide (GIP) /Glucagon like peptide-1 (GLP-1) /Glucagon tri-receptor agonist. An in-vitro cyclic AMP assay in human receptor- expressing CHO-K1 cells demonstrated that HISHS-30had a half-maximal effective concentration 2.9 and 6.5 fold higher than exendin-4 or GIP, respectively, and 355-fold lower than glucagon. Subcutaneous dosing every third day for 4 weeks in diabetic db/db mice of HISHS-30at 3 and 20 nmol/kg reduced HbA1c, body weight, triglycerides and glucagon levels robustly and markedly more than tirzepatide (Table) .Treatment with HISHS-30also led to an increase in serum and liver Fibroblast Growth Factor-21 (FGF-21) levels vs. tirzepatide.

In conclusion, HISHS-30is a potent, long acting GIP/GLP-1/glucagon tri-receptor agonist, with higher effects on glucose homeostasis and metabolic biomarkers in diabetic mice than tirzepatide.

Disclosure

V.S. Burade: None. A. Garcia-Ocana: Consultant; Sun Pharmaceutical Industries Ltd. R.E. Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. G.A. Rutter: Advisory Panel; Sun Pharmaceutical Industries Ltd. Research Support; Sun Pharmaceutical Industries Ltd. T. Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd. B. Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd., The Healthy Aging Company.
75-OR: IL-6R (Trans Signaling) Is a Major Modulator of Reverse Cholesterol Transport in Lipid-Laden Macrophages
Authors: ALRASHED FATEMA , ALZAQQAH FATEMAH , MADHOUN ASHRAF AL , ALQABANDI RAWAN , SINDHU SARDAR T. , ALMULLA FAHD , AHMAD RASHEED
Published: May 2022

The onset of obesity is vastly associated with low levels of high-density lipoprotein cholesterol (HDL-C) , which predisposes to cardiovascular diseases. Recently, mounting evidence indicates that IL-6 plays a key role in metabolism, especially in lipid metabolic homeostasis. Yet, the precise nature of the HDL/IL-6 dynamics has not been fully elucidated. Therefore, we evaluated the expression of IL-6 in circulatory monocytes of the individuals with various body mass index and we also determined their lipid profile. Our data show that monocytic IL-6 expression was found to be negatively associated with HDL-C levels in obese individuals and positively associated with C-reactive protein and other monocytic pro-inflammatory markers. Mechanistically, chemical inhibition or genetic silencing of IL-6 receptor gp130/IL-6ST gene induced severe upregulation of intracellular lipid accumulation in THP-1 transformed macrophages that was found to be further augmented under fatty acid rich culture conditions. Moreover, analysis of the genes involved in lipid and cholesterol metabolism showed up-regulation of the LDLR along with a remarkable inhibition of ATP Binding Cassette (ABC) Subfamily transporters ABCG1 and ABCB1. We also found that the macrophages lacking gp130/IL-6 receptors had very low beta-oxidation genes expression (CPT1A and CPT2) , however, with no effect on triglyceride synthesis genes expression (DGAT, ACACA, FASN and Srebp1c) .

In conclusion, our data support a role for IL-6 receptor signaling pathways in lipid alteration and cholesterol efflux which may have potential as a therapeutic target for metabolic syndrome.

Disclosure

F.Alrashed: None. F.Alzaqqah: None. A.Al madhoun: None. R.Alqabandi: None. S.T.Sindhu: None. F.Almulla: None. R.Ahmad: None.

Funding

(KFAS) (Grant #: RA AM 2016-007)
752-P: Study Design and Baseline Profile for Patients with Type 2 Diabetes in the Semaglutide Once-Weekly Randomized Pragmatic Trial (SEPRA)
Authors: WILLEY VINCENT , BUSE JOHN B. , HARTY BRIAN , MITCHELL JULIE L. , SOULE BENJAMIN P. , CHRISTENSEN HELENE N. , CZIRAKY MARK J. , SKIBSTED SIMON
Published: May 2022

SEPRA (NCT03596450) is a 2-yr, multicenter, open-label, randomized pragmatic clinical trial comparing the long-term effects of once-weekly subcutaneous semaglutide vs. standard of care (both added to ≤2 oral antidiabetic medications) in US health-insured adults with T2D and physician-determined inadequate glycemic control. SEPRA will assess glycemic control, weight loss, healthcare utilization, and patient-reported outcomes by collecting individual-level data from routine clinical practice and health insurance claims. The primary endpoint is the proportion of patients achieving HbA1c <7.0% at yr 1. The study design was evaluated using the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) -2 assessment; it scored 4-5 in all 9 domains, suggesting a highly pragmatic study. Of 1,278 patients enrolled, 54% were male with mean (± SD) age 57.4 ± 11.1 yrs, BMI 35.7± 8.0 kg/m2, diabetes duration 7.4 ± 6.0 yrs, HbA1c 8.48 ± 1.6%, and mean individualized HbA1c target 6.66 ± 0.5%. Of note, 86.9% of patients had HbA1c >7.0% and most required sizeable reductions in HbA1c to reach the clinician-assigned individualized target. SEPRA will provide real-world evidence on the long-term effectiveness of semaglutide in a population with a broad range of HbA1c levels and other clinical characteristics when used as intensification early on in usual T2D care practice settings.

Disclosure

V.Willey: Employee; HealthCore Inc. J.B.Buse: Consultant; Alkahest, Anji, AstraZeneca, Boehringer Ingelheim International GmbH, Cirius Therapeutics, Inc., Eli Lilly and Company, Fortress biotech, GentiBio, Glycadia, Glyscend, Janssen Pharmaceuticals, Inc., Mellitus Health, Moderna, Inc., Pendulum Therapeutics, Praetego, LLC, Stability Health, Valo, Zealand Pharma A/S, Other Relationship; Adocia, AstraZeneca, Eli Lilly and Company, Intarcia Therapeutics, Inc., MannKind Corporation, Novo Nordisk, Sanofi, Senseonics, vTv Therapeutics, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, vTv Therapeutics, Stock/Shareholder; Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Praetego, LLC, Stability Health. B.Harty: None. J.L.Mitchell: None. B.P.Soule: Employee; Bristol-Myers Squibb Company, Novo Nordisk. H.N.Christensen: Employee; Novo Nordisk. M.J.Cziraky: None. S.Skibsted: Employee; Novo Nordisk.

Funding

Funded by Novo Nordisk Inc
758-P: A Randomized Crossover Trial to Compare Automated Insulin Delivery with Carbohydrate Counting or Simplified Qualitative Meal-Size Estimation in Type 1 Diabetes
Authors: HAIDAR AHMAD , LEGAULT LAURENT , RAFFRAY MARIE , GOUCHIE-PROVENCHER NIKITA , JAFAR ADNAN , DEVAUX MARIE , GHANBARI MILAD , RABASA-LHORET RÉMI
Published: May 2022

We did a randomized crossover non-inferiority trial to compare 3 weeks of automated insulin delivery with (i) carbohydrate counting and (ii) qualitative meal-size estimation (low, medium, high, or very high carbohydrate (CHO)) in 30 adults with T1D (20/30 females, age 44±17 yrs, A1c 7.4±0.7%) . Low, medium, high, and very high CHO meals were defined as <30 g CHO, 30-60 g CHO, 60-90 g CHO, and >90 g CHO, respectively, and their prandial insulin boluses were calculated as the individualized insulin-to-CHO ratios x 15, 35, 65, and 95, respectively. Closed-loop algorithms were otherwise identical in the two arms. The time in range 3.9-10.0 mmol/L (primary outcome) was 74% (SD 10%) with carbohydrate counting and 71% (11%) with qualitative meal-size estimation; difference -3.6% (95% CI, -0.6% to -6.5%) which crossed the pre-specified non-inferiority margin of 4%. Times <3.9 mmol/L and <3.0 mmol/L were low in both two arms. Automated basal insulin delivery was higher in the qualitative meal-size estimation arm (34.6 vs. 32.6 u/day, p=0.003) . We conclude that non-inferiority of the qualitative meal-size estimation was not confirmed, though this method achieved a high time in range and low time in hypoglycemia. The qualitative meal-size estimation method may benefit from larger prandial boluses and more responsive post-meal automatic basal delivery.

Disclosure

A.Haidar: Consultant; Eli Lilly and Company, Research Support; ADOCIA, Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. L.Legault: Advisory Panel; Abbott Diabetes, Insulet Corporation, Novo Nordisk A/S, Other Relationship; Eli Lilly and Company, Research Support; AstraZeneca, Merck & Co., Inc. M.Raffray: None. N.Gouchie-provencher: None. A.Jafar: None. M.Devaux: None. M.Ghanbari: None. R.Rabasa-lhoret: Consultant; HLS Therapeutics Inc., Pfizer Inc., Other Relationship; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Canadian Institutes of Health Research, Cystic Fibrosis Canada, Diabetes Canada, Fondation Francophone pour la Recherche en Diabète (FFRD) , JDRF, National Institutes of Health, Société Francophone du Diabète (SFD) , Speaker's Bureau; Canadian Medical & Surgical Knowledge Translation Research Group (CMS) , CPD Network, Tandem Diabetes Care, Inc.

Funding

National Institutes of Health (1DP3DK106930-01)
76-LB: Performance of FreeStyle Libre 3 System
Authors: KARINKA SHRIDHARA A. , BRAZG RONALD L. , CASTORINO KRISTIN N. , LILJENQUIST DAVID R. , KIPNES MARK , LIU HANQING
Published: May 2022

FreeStyle Libre 3 is the next generation FreeStyle Libre system with the same sensor tail but an on-body component that is about 70% smaller than Libre 2. We evaluated the accuracy of the FreeStyle Libre 3 system in people with diabetes ages 4 years or older at 4 U.S sites. This was a non-randomized, multi-center, single-arm study with 100 evaluable subjects (95 subjects aged 6 years or older) on intensive insulin therapy. Subjects 6 years or older participated in up to 3 in-clinic sessions of up to 8 hours each over the 14- day wear period to obtain YSI comparator data. No glycemic challenges were performed during these sessions. For 5 subjects in the 4-5 years age group, capillary fingerstick measurements were performed during one in-clinic session to obtain SMBG comparator data. System performance was evaluated in terms of percent accuracy with respect to venous plasma reference using the YSI2300 Stat glucose analyzer. Accuracy was characterized as the proportion of sensor results that were within ±15%, ± 20%, and ± 40% of their paired YSI values for glucose levels ≥ 70 mg/dL or within ± 15 mg/dL, ± 20 mg/dL, and ± 40 mg/dL of YSI for glucose levels < 70 mg/dL. Other accuracy metrics such as mean bias and mean absolute relative difference (MARD) of the FreeStyle Libre 3 System with respect to YSI were also evaluated and are presented in Table 1. The FreeStyle Libre 3 System showed 93.2 % of values within ±20mg/dL/±20% of the YSI reference with an overall MARD of 7.9% based on the data from the 95 subjects with YSI reference.

Disclosure

S. A. Karinka: Employee; Abbott Diabetes. R. L. Brazg: Research Support; Abbott Diabetes, Lilly Diabetes, Medtronic, Novo Nordisk, Roche Diagnostics, Senseonics. K. N. Castorino: Consultant; Lilly Diabetes, Research Support; Abbott Diabetes, Dexcom, Inc., Drawbridge Health, Inc., Eyenuk, Inc., Laxmi Therapeutic Devices, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Speaker’s Bureau; Dexcom, Inc. D. R. Liljenquist: None. M. Kipnes: None. H. Liu: Employee; Abbott Diabetes.

Funding

Abbott Diabetes Care
770-P: Treatment Satisfaction and Fear of Hypoglycemia in the ADAPT Study: A Six-Month, Randomized Controlled Trial Comparing an Advanced Hybrid Closed-Loop System to Multiple Daily Injections (MDI) with Intermittently Scanned CGM (isCGM)
Authors: DE PORTU SIMONA , CHOUDHARY PRATIK , KROEGER JENS , THIVOLET CHARLES , EVANS MARK , RÉ ROSELINE , DE GROOT LINDA VORRINK , SHIN JOHN , GHEBRETINSAE AKLILU HABTEAB , CASTAÑEDA JAVIER , COHEN OHAD ,   ADAPT STUDY GROUP
Published: May 2022

Objective: To assess the effect of the MiniMed™ 780G Advanced Hybrid Closed Loop (AHCL) system compared to MDI with isCGM (MDI+isCGM) therapy on treatment satisfaction (TS) and fear of hypoglycemia (FoH) , in adults with type 1 diabetes (T1D) with above-target baseline glycemic control participating in the ADAPT study.

Methods: Participants with T1D who were on MDI+isCGM and who had suboptimal glycemic control (HbA1c≥8%) were randomly assigned to AHCL or to continue MDI+isCGM. Treatment satisfaction was measured with the Diabetes-Treatment-Satisfaction-Questionnaire, status (DTSQs) and change (DTSQc) and FoH with the Hypoglycemia Fear Survey (HFS) .

Results: Overall, the decrease in HbA1c was 1.4% greater in the AHCL group vs. MDI+isCGM group (P<0.001) with no difference in hypoglycemia. Mean DTSQs score increased significantly in the AHCL arm after 6 months compared to the MDI+isCGM arm (29.7 vs. 21.9, P=0.0003) , with significant improvement in perceived frequency of hyperglycemia (P<0.001) . There was no difference in the perceived frequency of hypoglycemia. Results were consistent in both DTSQs and DTSQc. Fear of hypoglycemia decreased in both groups, but the decrease was significantly greater in the AHCL group. At 6 months, HFS scores decreased by 10.2 points and 2.7 points from baseline in the AHCL and MDI+isCGM groups, respectively (P=0.04) .

Conclusion: AHCL therapy improves patient-reported outcomes with greater treatment satisfaction and reduced FoH compared to MDI+isCGM in sub-optimally controlled participants with T1D.

Disclosure

S.De portu: Employee; Medtronic. J.Castañeda: Employee; Medtronic. O.Cohen: Employee; Medtronic. Adapt study group: n/a. P.Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. J.Kroeger: Advisory Panel; Abbott Diabetes, Dexcom, Inc., Other Relationship; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Tandem Diabetes Care, Inc., Research Support; Medtronic. C.Thivolet: Board Member; Insulet Corporation, Medtronic, Research Support; Abbott Diabetes, Lilly Diabetes, Novo Nordisk A/S, Sanofi. M.Evans: Advisory Panel; Pila Pharma, Zucara Therapeutics, Other Relationship; Abbott Diabetes, Dexcom, Inc., Medtronic, Novo Nordisk, Research Support; AstraZeneca, Sanofi, Speaker's Bureau; Lilly Diabetes. R.Ré: Employee; Medtronic. L.Vorrink de groot: Employee; Medtronic. J.Shin: Employee; Medtronic. A.Habteab ghebretinsae: None.

Funding

Medtronic
774-P: Impact of Transition to Tandem Control-IQ on Sleep Awakenings in Youth with Type 1 Diabetes (T1D) and Their Parents
Authors: KARAMI ANGELA J. , PYLE LAURA , VIGERS TIMOTHY B. , JOST EMILY , WADWA R. PAUL , COBRY ERIN C.
Published: May 2022

Youth with T1D and their parents are susceptible to diabetes-related nocturnal awakenings, which have been associated with reduced sleep duration and quality. We conducted an observational study of youth with T1D starting on the Tandem Control-IQ (CIQ) hybrid closed-loop (HCL) system to evaluate the impact of system use on sleep.

Thirty-nine youth (age 11.1±3.6 yrs, T1D duration 2.5±3.0 yrs, 54% male) and a parent (age 42.5±6.7 yrs, 18% male) completed sleep diaries capturing the number of and reasons for nocturnal awakenings over a 7-day period. Analyses compared diaries from before starting CIQ (baseline) to 3- and 6-months after starting CIQ using a zero-inflated Poisson mixed model with random intercept for participants.

Youth and parents reported significantly fewer total awakenings per night at 3- and 6-months compared to baseline (Table) . A significant decrease in diabetes-related awakenings was observed after 6 months in youth but not in parents.

Following CIQ initiation, fewer nocturnal awakenings were reported by parents and youth, with youth additionally reporting significantly fewer diabetes-related awakenings at 6 months. Due to the subjective nature of diaries, the number of true awakenings may be different. The results suggest that HCL technology may be beneficial in reducing sleep disruptions in youth and parents.

Disclosure

A.J.Karami: None. L.Pyle: None. T.B.Vigers: None. E.Jost: Other Relationship; Tandem Diabetes Care, Inc. R.Wadwa: Advisory Panel; Dompé, Consultant; Beta Bionics, Inc., Other Relationship; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. E.C.Cobry: None.
79-OR: Conventionalization from Cecal Transplant Recipients Protects Against Type 1 Diabetes Development in Germ-Free NOD Mice
Authors: PAN SAMUEL , ZHANG XUE-SONG , BLASER MARTIN J.
Published: May 2022

Early-life antibiotic exposure perturbs the microbiome, dysregulates intestinal immune gene expression, and accelerates and amplifies type 1 diabetes (T1D) development in NOD mice. We have previously shown that cecal microbiota transfer (CMT) from healthy donors rescues antibiotic-induced T1D development via restoration of intestinal microbiota and baseline immune parameters. To better understand the role of specific members of the gut microbiome in T1D development, we conventionalized germ-free (GF) recipients with cecal microbiota from three donor mouse groups that had been treated as follows: 1) [Control] received PBS only; 2) [Antibiotic] (tylosin) -disrupted microbiome; and 3) given tylosin as in 2) , followed by cecal microbiota gavage [CMT-restored microbiome]. In the now-conventionalized mice, those that received the CMT-restored microbiome had a lower rate of T1D development than those that received the antibiotic-perturbed microbiota. This showed that the disease phenotypes in one generation can be transferred into the next. Conventionalization with the CMT-restored microbiota led to the most diverse microbiomes and lowest expression of antimicrobial, immune and mucin genes. Surprisingly, gavage with the Control inoculum failed to protect the conventionalized recipients against T1D development compared with the antibiotic group, led to low diversity microbiomes, low abundance of taxa S24-7 and Oscillospira, and increased expression of antimicrobial, immune, and mucin synthesis genes. We conclude that: 1) The CMT protective effect is transferrable to the next generation, and 2) the very low density of S24-7 and Oscillospira in the GF recipients conventionalized with the Control inoculum led to decreased microbiome richness and evenness, increased gene expression, and loss of T1D protection. The effects of these two taxa on T1D development in NOD mice should be further studied.

Disclosure

S.Pan: None. X.Zhang: None. M.J.Blaser: None.

Funding

National Institutes of Health (UAI22285) ; Fondation LeDucq (TransAtlantic Program 17CVD01)
791-P: Clinical Data of a New Insulin Micropump System in Children with Type 1 Diabetes Mellitus (T1DM)
Authors: RISTA LUCAS , FLORES ADRIANA , RIVERS MEREDITH , VULCANO CRISTINA , REPETTO ENRICO
Published: May 2022

Background: To maintain glucose control in T1DM is especially difficult in children that have unpredictable amounts of physical activity and broad eating patterns. Advances in diabetes technology include Continuous Subcutaneous Insulin Infusion (CSII) and patch/tubeless micropumps are newer options available. Patch pumps are free of tubing, small and lightweight. We aimed to report the initial clinical effect of an insulin micropump therapy in a cohort of children with T1DM.

Method: We studied pediatric patients (5-years old) , converting from multiple daily injections of insulin (MDI) to Roche Accu-chek Solo tubeless micropump system. Nine children (5 female/4 male) were followed during 1 and 3 months. All patients used Continuous Glucose Monitoring (CGM) and data was collected to learn time spent in hypoglycemia, normoglycemia and hyperglycemia, as well the glucose variability.

Results: Data from this small cohort showed that basal insulin infusion rates at baseline and 3 months were similar (7.7U to 7.6U) and insulin bolus requirements reduced from 14.3U to 12.7U, respectively. Based on CGM analysis the table below shows the % of time spent at different glycemia values (mean/SD) , as well its variability. HbA1c was 7.3% at baseline and 7.4% after 3 months, and there were no emergency room admissions due to severe hypoglycemia.

Conclusion: The initial results of this new insulin micropump therapy in children showed an improvement on glucose control and variability, without increasing hypoglycemia. Additional studies are necessary to demonstrate the medium and long-term effect of this new device in this population.

Disclosure

L. Rista: Advisory Panel; Roche Diabetes Care. Speaker's Bureau; AstraZeneca, Novo Nordisk. A. Flores: Speaker's Bureau; Novo Nordisk, Roche Diabetes Care, Sanofi. M. Rivers: Employee; Roche Diabetes Care. C. Vulcano: Employee; Roche Diabetes Care. E. Repetto: Employee; Roche Diabetes Care.
799-P: Cognitive Assessment in Elderly with Type 1 Diabetes Mellitus on Insulin Pump: A Cross-Sectional Observational Study
Authors: RIZZI ALESSANDRO , QUARANTA DAVIDE , L’ABBATE FEDERICA , MASONEIACOBUCCI GIOVANNA , TARTAGLIONE LINDA , LEO LAURA , RIZZO GAETANO EMANUELE , MARRA CAMILLO , DESIDERI GIOVAMBATTISTA , PITOCCO DARIO
Published: May 2022

Aims: Aim of the study was to investigate cognitive performance in elderly with type 1 diabetes (T1DM) on insulin pump (CSII) and the correlation between time in range (TIR) and cognitive scores (CS) . Differences in CS according to duration of disease were also investigated.

Methods: Subjects with T1DM older than 65 years, on CSII were included. Participants underwent following tests: Rey Auditory Verbal Learning Test (RAVLT) , Rey-Osterrieth Figure Test, Verbal Fluency Test, Stroop Color and Word Test and Trail Making Test (TMT) A and B. At visit data from continuous glucose monitoring, according to 20Advanced Technology and Treatments in Diabetes Consensus, data on diabetic history and blood tests were collected.

Results: We enrolled 45 subjects, 22 women (49%) , mean age 69.5 years. Median duration of disease was 30 years; mean HbA1c was 58 mmol/mol (7.4%) . Mean TIR was 66%, mean time below range was 2.62% and time above range (TAR) 29.9%. 5 subjects (11%) presented CS compatible with mild cognitive impairment. No correlation between TIR and CS was detected. Dividing study population on median duration of disease, subjects with longer history presented lower TIR (59.7 % (20.2) vs. 71.1% (16.3) , p=0.05) and higher TAR (35.7% (17.8) vs. 25.2% (15.3) , p=0.05) . In both groups 26% were using advanced hybrid closed loop systems. Subjects with longer history presented lower scores at RAVLT-Immediate recall (30.1 (12.6) vs. 39.3 (13.4) , p<0.001) and RAVLT-Accuracy (0.89 (0.09) vs. 0.93 (0.05) , p=0.08) and longer time at Stroop-Test (28.8 (8.13) vs. 20.0 (7.36) , p<0.001) and TMT-B (131 (64.2) vs. 1 (32.2) , p=0.08) test. Groups were comparable for school age (>30 years 12.9 vs. <30 years 13.1, p=0.80) .

Conclusions: Elderly with T1DM presented good TIR and at, a deep evaluation, they presented good CS. Those with longer history presented lower CS in executive and attentive functions, expression of cerebral subcortical damage. No association between TIR and CS was detected.

Disclosure

A.Rizzi: None. D.Pitocco: None. D.Quaranta: None. F.L'abbate: None. G.Masoneiacobucci: None. L.Tartaglione: None. L.Leo: None. G.Rizzo: None. C.Marra: None. G.Desideri: None.
804-P: Barriers and Concerns Regarding Initiating Insulin Therapy among People with Type 2 Diabetes
Authors: STEVENSON JULIA , XU EMILY , MONROY-SPANGENBERG ERIK , YE EMILY , WOOD RICHARD
Published: May 2022

Background: As Type 2 diabetes (T2D) progresses, initiation of insulin therapy may become necessary to maintain glycemic management and prevent further health complications; however, therapeutic inertia in insulin initiation is common. This study aimed to understand perceptions of and barriers towards insulin therapy among people with T2D.

Methods: In December 2021, 1,939 non-insulin-using adults with T2D responded to an online questionnaire. Those whose doctor had previously discussed insulin therapy with them (n=143) completed a series of questions evaluating perceptions and barriers toward insulin on a 5-point Likert scale and indicated their preferred alternatives to starting insulin. Health and demographic information were collected.

Results: Nearly three quarters (73%) cited worries that once they start taking insulin, they would have to take it for the rest of their life. Over half (58%) felt that starting insulin would mean they were not adequately taking care of their diabetes, and 44% felt upset when their doctor first brought up insulin therapy. Concerns about weight gain (49%) , hypoglycemia (48%) , and hesitancy toward injections (43%) were also common. Only 22% felt confident that taking insulin would improve their diabetes management, and 69% believed they could improve their diabetes management without insulin. The most common preferred steps instead of starting insulin were altering diet (70%) and exercising more frequently (64%) ; 43% would rather start taking a new oral drug, while fewer would try a non-insulin injectable medication (22%) .

Conclusions: Insulin initiation may be associated with not only undesirable side effects, but also negative emotions and self-perceptions in adults with T2D. Many do not see insulin as necessary for improving their diabetes management and would prefer to make other changes. A better understanding of perceptions towards insulin therapy can help inform approaches to care.

Disclosure

J.Stevenson: Other Relationship; Abbott Diabetes, Ascensia Diabetes Care, Beta Bionics, Inc., Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, LifeScan, Medtronic, Roche Diabetes Care, Tandem Diabetes Care, Inc. E.Xu: Employee; dQ&A. E.Monroy-spangenberg: Employee; dQ&A, Stock/Shareholder; Senseonics. E.Ye: Employee; dQ&A. R.Wood: Other Relationship; Multiple companies and patient organizations (>10) .
816-P: Bioprinted Allogeneic Islet–Containing Implants Normalize Blood Glucose Control in Diabetic Rat Models without Immune Suppression
Authors: RUSSO VALERIO , JALILI REZA , YU YANG , AGARWAL RISHIMA , PAN SHENG , HAKIMI NAVID , JAHAN KAUSHAR , WILTS EMILY M. , IDA SHOGO , GETSIOS SPIRO , KIEFFER TIMOTHY J. , WADSWORTH SAM
Published: May 2022

Transplantation of cadaveric islets can reverse type 1 diabetes (T1D) but requires life long immunosuppression. Cell encapsulation has potential to overcome this challenge by blocking immune cell access to islet grafts while allowing nutrient exchange, glucose sensing and insulin release. In this study, 3D tissues consisting of patterned, multi-shell fibres with an islet-containing core and immunoprotective shell were manufactured using Aspect Biosystems’ microfluidic 3D bioprinting technology for implantation in diabetic rats. Blood glucose and animal body weight were monitored for several months following surgery. Upon retrieval, bioprinted tissues were assayed for islet cell viability and function by glucose-stimulated insulin secretion (GSIS) , followed by histology and immunohistochemistry (IHC) to analyze foreign body response (FBR) and immune cell infiltration. 3D bioprinted implants containing reaggregated allogeneic rat islets re-established normoglycemia for > 90 days in streptozotocin-treated diabetic immunodeficient rats, and > 30 days in diabetic immunocompetent rats. Post-retrieval, tissue implants demonstrate high viability and functionality, with absence of immune cell penetration through the shell, confirming its immune protective properties. Modification of the outer shell biomaterial to reduce FBR was shown to extend islet tissue implant functionality. This is the first study describing a 3D bioprinted implant composed of a core/shell micro-fibre used to deliver therapeutic islets into diabetic animals. The promising results obtained in rodent models open the door to further testing in larger animal models and, eventually, T1D patients.

Disclosure

V.Russo: None. S.Getsios: None. T.J.Kieffer: Consultant; Fractyl Health, Inc., Sigilon Therapeutics, Inc., Employee; ViaCyte, Inc., Research Support; Aspect Biosystems. S.Wadsworth: None. R.Jalili: None. Y.Yu: None. R.Agarwal: None. S.Pan: None. N.Hakimi: None. K.Jahan: None. E.M.Wilts: None. S.Ida: None.

Funding

National Research Council Canada - Industrial Research Assistance Program (#935249) , Canadian International Innovation Program (#938664) , Genome British Columbia (#GEN009) , Stem Cell Network (#FY20/FBP-7 Kieffer) , Mitacs (#IT19764) ,
819-P: Long-Term Testosterone Treatment Improves Liver Function Parameters in Men with Hypogonadism and Type 2 Diabetes Mellitus: Real-World Data from a Registry
Authors: SAAD FARID , HAIDER KARIM S. , HAIDER AHMAD
Published: May 2022

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with hypogonadism and T2DM is high. Most of these patients are obese.

Methods: Of 370 men with hypogonadism and T2DM, 190 received testosterone undecanoate 1000 mg/12 weeks (T-group) , 180 opted against treatment (CTRL) . Means and standard deviations of absolute measures over 13 years are reported. Fatty liver index (FLI) was calculated using the formula by Bedogni.

Results: Mean baseline age: 62.0±5.2, mean (median) follow-up: 9.3±3.1 (10) years. γ-GT (U/L) decreased from 43.9±22.9 to 21.9±6.8 in the T-group and increased from 35.2±11.3 to 62.3±6.7 in CTRL (p<0.00for both) . Triglycerides decreased from 3.5±0.6 to 2.2±0.1 in T-group and increased from 3.1±0.6 to 3.8±0.8 in CTRL (p<0.00for both) . Waist circumference (cm) decreased from 117.9±14.8 to 98.2±4.3 in the T-group (p<0.0001) and increased in CTRL from 116.9±13.5 to 119.0±8.4 (p<0.0001) .

BMI (kg/m2) decreased from 36.5±4.4 to 28.5±2.4 in the T-group (p<0.0001) and increased in CTRL from 32.8±4.7 to 33.3±3.6 (p<0.0001) . AST (U/L) decreased from 39.0±12.8 to 20.8±1.8 in the T-group and increased from 28.6±9.5 to 55.7±10.8 in CTRL (p<0.00for both) . ALT (U/L) decreased from 42.4±13.0 to 24.7±2.0 in the T-group and increased from 32.8±10.0 to 62.3±13.2 in CTRL (p<0.00for both) . FLI decreased from 95.1±6.0 to 63.8±11.3 in the T-group and increased from 90.2±10.8 to 96.2±4.4 in CTRL (p<0.00for both) .

Conclusions: Long-term testosterone therapy in men with hypogonadism and T2DM improved surrogate parameters of liver function indicating an improvement in NAFLD. All paramters deteriorated in untreated controls.

Disclosure

F.Saad: Consultant; Bayer AG, Stock/Shareholder; AbbVie Inc., Bayer AG, GlaxoSmithKline plc. K.S.Haider: Other Relationship; Bayer AG. A.Haider: Other Relationship; Bayer AG.

Funding

Bayer AG