bluuebunny/crossref_metadata_2025_split huggingface dataset:
741-P: Avoiding Type 2 Diabetes after Pancreas Transplantation—A Look into Pancreas Plasticity
Authors: MCCUNE KASI R. 
Published: June 2023

Purpose: Weight gain often coincides with aging. Post pancreas transplant, can allografts compensate to the added body mass?
Methods: We conducted a retrospective review of pancreas transplant at CUIMC from 1/1/08-11/1/22. All were &gt;18 yo and underwent simultaneous kidney pancreas transplant, pancreas after kidney, or pancreas alone. Patients with &lt;1yr graft survival were excluded. We compared recipient and donor factors of recipients with functional grafts (FF) vs those with post-transplant graft dysfunction (PTGD).
Results: 121 patients were included. BMI at evaluation 24.2±3.2kg/m2. 11.6% had T2DM. Pre-operative A1C was 8.2±1.7%. Donor age was 24.7±11yo with BMI 23.7±6kg/m2. 20 (17%) of recipients developed PTGD defined as an A1C&gt;6.5% or need for diabetes medication. 50% of PTGD had BMI gain &gt;5kg/m2 vs 25% FF (p=0.01). Most recent A1C 6.8±4% PTGD vs 5.3±3.5% FF (p&lt;0.01). Donor age was higher in PTGD vs FF (29.6±10.5 vs 23.7±10.9 yo, p=0.03) On subanalysis of those who increased BMI &gt;5kg/m2, donor age &gt;30yo was associated with PTGD (p=0.03) (Fig 1). Comparing donor age &gt;or&lt;30yo, odds of PTGD with BMI gain was 12X with donors &gt;30yo vs 1.2X with donors &lt;30yo. Factors associated with BMI increase were age &lt;40yo at transplant and BMI &gt;25kg/m2 at evaluation.
Conclusions: When transplanting a patient &lt;40yo with a BMI&gt;25kg/m2, consider that they have an increased risk of weight gain after transplant and use a graft &lt;30yo.

Disclosure
K.R.Mccune: None.
749-P: Selection of BI 456906 as a Dual GCGR/GLP-1R Agonist Based on In Vitro Potency and In Vivo Target Engagement Biomarkers
Authors: AUGUSTIN ROBERT , THOMAS LEO , ZIMMERMANN TINA , SIMON ERIC , RIST WOLFGANG , UPHUES INGO , REINDL WOLFGANG , KLEIN THOMAS , NEUBAUER HEIKE 
Published: June 2023

Glucagon (GCG) and glucagon-like peptide 1 (GLP-1) are peptide hormones that pharmacologically regulate bodyweight by increasing energy expenditure and reducing energy intake, respectively. Several dual (GCG receptor [GCGR]/GLP-1 receptor [GLP-1R]) agonistic peptides are in clinical development for obesity. We describe preclinical data leading to selection of BI 456906 as a dual agonist. Functional potencies of the compounds were determined in CHO-K1 cells stably expressing human GCGR and GLP-1R. EC50 for GCGR mediated cAMP increase were 0.52 nM for BI 456906, 0.92 nM for BI 456908 and 0.44 nM for BI 456987. EC50 for GLP-1R engagement were 0.33 nM, 0.61 nM and 1.43 nM, respectively. Upon acute, single dosing to lean mice, engagement of the GCGR and GLP-1R was determined by testing for improvement in oral glucose tolerance (30 nmol/kg) and increase in plasma FGF-21 and liver nicotinamide N-methyltransferase mRNA expression (100 nmol/kg), respectively. Specificity of the biomarkers was confirmed using the selective GLP-1R agonist semaglutide and GLP-1R knockout mice. Bodyweight and glucose lowering (HbA1c) efficacies were investigated in subchronic dosing studies in diet-induced obese (DIO) and diabetic (db/db) mice, respectively. In DIO mice, BI 456906 (30 nmol/kg qd), BI 456908 (30 nmol/kg qd) and BI 456897 (10 nmol/kg qd) achieved bodyweight lowering from baseline of 25%, 27%, and 26%, respectively. In db/db mice, BI 456906 and BI 456908 (10 and 20 nmol/kg qd) substantially lowered HbA1c (0.4-0.6%); no clear effect was observed for BI 456897 (3 and 7 nmol/kg qd). As a balanced GCGR/GLP-1R agonist with robust in vivo efficacy BI 456906 (30 nmol/kg qd) was further characterized, and superior bodyweight lowering (32% vs 27%; p&lt;0.05) was seen versus a maximally effective semaglutide dose (100 nmol/kg qd). This was attributed to an increase in energy expenditure. The selected candidate, BI 456906, is currently in clinical development in people with obesity and NASH.

Disclosure
R.Augustin: None. L.Thomas: Employee; Boehringer Ingelheim Pharma GmbH&Co.KG. T.Zimmermann: Employee; Boehringer Ingelheim Pharma GmbH&Co.KG. E.Simon: Employee; Boehringer Ingelheim Pharma GmbH&Co.KG. W.Rist: None. I.Uphues: Employee; Boehringer Ingelheim Pharma GmbH&Co.KG. W.Reindl: None. T.Klein: Employee; Boehringer Ingelheim Pharma GmbH&Co.KG. H.Neubauer: None.

Funding
Zealand Pharma A/S; Boehringer Ingelheim
751-P: Longer Time Spent in Glycemic Control after Initiating Tirzepatide vs. Comparators—Exploratory Analysis of SURPASS 1–5 Trials
Authors: ROSENSTOCK JULIO , GARVEY W. TIMOTHY , BATTERHAM RACHEL L. , LIU MINZHI , BERGMAN BRANDON , HEMMINGWAY ANDREA , THIEU VIVIAN 
Published: June 2023

Conventional trials in people with T2D typically report HbA1c at study end as the primary outcome. In SURPASS 1-5 trials, 81-97% of adults with T2D treated with the GIP/GLP-1 receptor agonist tirzepatide (5, 10, or 15 mg) achieved an HbA1c &lt;7.0% at the primary endpoint. Here we report the time spent in glycemic control throughout the duration of each trial. Participants were randomized to tirzepatide (5, 10, or 15 mg) or comparator (placebo in SURPASS 1 and 5, semaglutide 1 mg in SURPASS 2, insulin degludec in SURPASS 3, and insulin glargine in SURPASS 4), with primary treatment durations of 40 or 52 weeks (wks). Continuous time spent with HbA1c &lt;7.0% was descriptively analyzed in all patients on treatment without rescue medication, with missing data imputed, in this post-hoc analysis. Participants on tirzepatide 5, 10, or 15 mg spent longer time with HbA1c &lt;7.0% than comparators. In studies of 40 wks duration, median time spent with HbA1c &lt;7.0% was 32 wks for all tirzepatide doses, 28 wks for semaglutide 1 mg, and 0 wks for placebo. In studies of 52 wks, this was up to 44 wks for tirzepatide, 32 wks for insulin degludec, and 12 wks for insulin glargine. Time spent with HbA1c &lt;7.0% was generally similar across all tirzepatide doses in each study. To conclude, tirzepatide allowed greater continuous time spent with HbA1c &lt;7.0% vs placebo, semaglutide 1 mg, and basal insulins.

Disclosure
J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. W.Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens. R.L.Batterham: Advisory Panel; Novo Nordisk, GlaxoSmithKline plc., Gila Therapeutics Ltd, Pfizer Inc., Consultant; Eli Lilly and Company, Novo Nordisk, Epitomee, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, GlaxoSmithKline plc. M.Liu: Consultant; Eli Lilly and Company. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Hemmingway: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. V.Thieu: None.

Funding
Eli Lilly and Company
752-P: Improved BMI Category Is Associated with Better Patient-Reported Outcomes (PROs) in Adults with T2D Treated with Tirzepatide
Authors: LEE CLARE , BOYE KRISTINA , THIEU VIVIAN , ALLEN SHERYL , DONG WENXIU , SAPIN HELENE 
Published: June 2023

Treatment with tirzepatide, a first-in-class GIP/GLP-1 receptor agonist, resulted in statistically and meaningfully reduced HbA1c, and substantially reduced weight, in adults with T2D in the Phase 3 SURPASS studies. We explored the association between shift in BMI category and PROs in adults treated with tirzepatide 5, 10, or 15mg in SURPASS-1 to -5.
Data from all SURPASS-1 to -5 tirzepatide-treated participants with non-missing BMI were pooled, regardless of tirzepatide dose assigned. Participants with ‘improved’ (≥1 category lower vs. baseline), ‘stable’, or ‘worsened’ (≥1 category higher vs. baseline) BMI category at endpoint were assessed using weight-related PRO instruments at baseline and endpoint - Impact of Weight on Self-Perceptions (IW-SP), Impact of Weight on Quality of Life-Lite-Clinical Trials (IWQOL-Lite-CT), and Ability to Perform Physical Activities of Daily Living (APPADL).
All PRO scores were greater at endpoint than at baseline for tirzepatide-treated participants with ‘improved’ or ‘stable’ BMI category (Table). Changes were numerically greater across all PROs for participants with ‘improved’ BMI category compared with those whose BMI category remained ‘stable’ or ‘worsened’.
Improvements in PRO scores were greater in tirzepatide-treated adults with T2D with improved BMI category than in those with stable or worsened BMI category.

Disclosure
C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.Boye: Employee; Eli Lilly and Company. V.Thieu: None. S.Allen: None. W.Dong: Employee; TechData Service Company, Other Relationship; Eli Lilly and Company, AstraZeneca. H.Sapin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
76-LB: Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA)–Experienced Adults with Type 2 Diabetes (T2D) Switching to Once-Weekly (OW) Semaglutide in a Real-World Setting—SURE Program Post Hoc Analysis
Authors: RUDOFSKY GOTTFRIED , MENZEN MARKUS , POTIER LOUIS , CATARIG ANDREI-MIRCEA , CLARK ALICE , PRIYADARSHINI PRACHI , ABREU CRISTINA 
Published: June 2023

Retrospective database studies have shown that switching between some GLP-1RAs may be associated with additional benefits on glycemic control and body weight (BW).
This prospective post hoc analysis of pooled data from the SURE real-world program (9 ~30 week studies in 10 countries) investigated outcomes associated with switching to OW semaglutide from another GLP-1RA in adults with T2D. Endpoints included change in HbA1c and BW from baseline to end of study, percentage achieving HbA1c &lt;7% (when baseline HbA1c ≥7%) or BW change ≥5%, and safety. For change in HbA1c and BW, a random coefficient-adjusted mixed analysis for repeated measures was used, regardless of semaglutide treatment status.
In total 651 participants (mean age 60 years; 53% male) switched to OW semaglutide: 64% from liraglutide, 31% from dulaglutide. Significant changes were observed in HbA1c and BW (Figure); 33% of participants with baseline HbA1c ≥7% achieved HbA1c &lt;7%, and 28% reduced BW by ≥5%. No new safety concerns were identified; 3% discontinued due to AEs, 2% reported ≥1 hypoglycemic episode (blood glucose &lt;54 mg/dL) and 8/11 participants with ≥1 level 2 hypoglycemic episode were on insulin.
In adults with T2D previously treated with GLP-1RAs, switching to OW semaglutide may provide additional benefits with convenient OW dosing.

Disclosure
G. Rudofsky: Consultant; AstraZeneca, Eli Lilly and Company, Speaker's Bureau; Abbott Diabetes, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Sanofi. M. Menzen: Advisory Panel; Boehringer Ingelheim Pharma GmbH&Co. KG, Novo Nordisk A/S, Ascensia Diabetes Care, Eli Lilly and Company, Novartis, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Santis, Boehringer Ingelheim Pharma GmbH&Co. KG, Novo Nordisk A/S, Bayer Inc., Eli Lilly and Company, Novartis. L. Potier: Consultant; Lilly Diabetes, Novo Nordisk, Sanofi, AstraZeneca, Boehringer Ingelheim Inc. A. Catarig: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. A. Clark: Employee; Novo Nordisk A/S. P. Priyadarshini: None. C. Abreu: Speaker's Bureau; Lilly, Novo Nordisk.

Funding
Novo Nordisk
766-P: Safety and Tolerability of Once-Weekly GL0034 (Utreglutide) in Healthy Individuals—A Multiple Ascending Dose Study
Authors: THENNATI RAJAMANNAR , BURADE VINOD S. , NATARAJAN MUTHUKUMARAN , SHAHI PRADEEP , NAGARAJA RAVISHANKARA , PANCHAL SATISH T. , AGRAWAL SUDEEP K. , JANDRAIN BERNARD , DUVAUCHELLE THIERRY , GARCIA-OCANA ADOLFO , RUTTER GUY A. , PRATLEY RICHARD E. , THORENS BERNARD , VILSBØLL TINA 
Published: June 2023

GL0034 (GL) is being developed as a once-weekly, long-acting glucagon-like peptide 1 receptor agonist (GLP-1RA). This phase 1 study assessed the safety and tolerability of multiple ascending doses of GL. Healthy individuals (N=36) with BMI 18 to 28 kg/m2 were randomized (9:3) to subcutaneous GL or placebo. Two groups of nine individuals each received a fixed dose of 450 μg (cohort 1) or 680 μg (cohort 2) during four weeks; a third group was treated for eight weeks, with two weekly doses of 450 μg, followed by two doses of 900 μg and four doses of 1,520 μg (cohort 3). Safety biomarkers and key exploratory pharmacodynamic effects including fasting insulin and glucose, alanine transaminase and body weight were assessed. GL related adverse effects were mainly gastrointestinal with dose-dependent nausea, vomiting and decreased appetite. Fasting insulin was decreased in cohort 2 and cohort 3 on day 23 and 51 respectively following treatment with GL with a corresponding reduction in homeostatic model assessment for insulin resistance (HOMA-IR). At day 51, alanine transaminase levels decreased from baseline in cohort 3 versus an increase in placebo. Dose-dependent decreases in body weight were measured in cohorts 1, 2 and 3, respectively, compared to baseline, and were sustained through days 50 and 78. In conclusion, GL was well tolerated and efficacious in healthy individuals with normal weight.

Disclosure
R.Thennati: None. A.Garcia-ocana: Consultant; Sun Pharmaceutical Industries Ltd. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. V.S.Burade: None. M.Natarajan: None. P.Shahi: None. R.Nagaraja: None. S.T.Panchal: None. S.K.Agrawal: None. B.Jandrain: None. T.Duvauchelle: None.
771-P: Tirzepatide Reduces HbA1c and Body Weight Significantly More than Placebo or Semaglutide Irrespective of Baseline Beta-Cell Function—Post Hoc Analysis from SURPASS-1 and SURPASS-2
Authors: MALDONADO JUAN M. , DE BLOCK CHRISTOPHE , FRIAS JUAN P. , LEE CLARE , BROWN KATELYN , WANG HUI , THOMAS MELISSA K. 
Published: June 2023

Tirzepatide (TZP), a once-weekly GIP/GLP-1 receptor agonist, achieved significantly greater HbA1c and body weight (BW) reductions with all doses (5, 10, 15 mg) vs placebo (SURPASS-1 [S-1]) and semaglutide (SEMA) 1 mg (SURPASS-2 [S-2]) in randomized Phase 3 trials in people with type 2 diabetes controlled by diet and exercise (S-1) or metformin (S-2). Exploratory post hoc analyses examined changes from baseline in HbA1c and BW in these studies at 40 weeks across HOMA2-B (C-peptide) and HOMA2-IR (insulin) quartiles (Q) from low (lower beta-cell function/insulin resistance) (Q1) to high (Q4) as assessed by mixed model repeated measures (MMRM). HbA1c reductions were greater with all TZP doses than placebo or SEMA within each HOMA2-B and HOMA2-IR baseline Q. HbA1c reductions were largest in people within HOMA-2B Q1, yet similar across all HOMA2-IR Qs (Fig). BW reductions were greater across Qs with all TZP doses (ranging from 6%-14%) than placebo (up to 2%) or SEMA (up to 7%). TZP was more efficacious than placebo or SEMA in reducing HbA1c and BW across a spectrum of pancreatic beta-cell function, notably achieving greater glycemic improvement in people with markers of diminished pancreatic beta cell function at baseline.

Disclosure
J.M.Maldonado: Employee; Eli Lilly and Company. C.De block: Advisory Panel; Abbott Diagnostics, Indigo Diabetes, Insulet Corporation, Eli Lilly and Company, Novo Nordisk, Research Support; Boehringer-Ingelheim, AstraZeneca, Indigo Diabetes, Eli Lilly and Company, Speaker's Bureau; Novo Nordisk. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.Brown: Employee; Eli Lilly and Company. H.Wang: None. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
78-LB: PK Studies in Rats and Minipigs of GB-7001, a Novel Monthly Microsphere Formulation Containing High Drug Content of Semaglutide
Authors: SEOL EUNYOUNG , KIM YEJIN 
Published: June 2023

Semaglutide, a once-weekly GLP-1 receptor agonist, has been developed as a treatment for type 2 diabetes and obesity. Currently, the longest-acting GLP-1 product (including dulaglutide, semaglutide, and tirzepatide) is a weekly injection, and there are no approved once-monthly long-acting injectables. There is a need for a product that lasts up to 1 month to improve patient convenience. GB-7001 is a monthly injectable with high content of semaglutide under development with an improvement that reduces the side effect of existing microspheres. The goal of this study is to investigate the pharmacokinetics (PK) of GB-7001 in rats and minipigs. Pharmacokinetic evaluation in rats and minipigs was performed by a single subcutaneous injection, and semaglutide concentration in serum was analyzed by liquid chromatography-tandem mass spectrometry. GB-7001 had a spherical shape with a D50 value of 34.4 µm. The drug content of semaglutide was determined to be 18.0%. Regardless of the high drug content, the sustained release of GB-7001 was shown for up to 28 days without an initial burst and without a lag phase. Although the release rate of GB-7001 slows after 28 days, semaglutide was detected within the quantifiable range for up to 56 days.
In conclusion, GB-7001 is an improved 1-month semaglutide injectable that has shown promising results in PK studies in rats and minipigs. Further preclinical studies of the final formulation are scheduled, and GB-7001 is planned to apply for IND once the final formulation is selected.

Disclosure
E. Seol: None. Y. Kim: None.

Funding
Ministry of Health & Welfare, Republic of Korea (HI21C1732)
782-P: Efficacy of Tirzepatide in People with Young-Onset T2D in the SURPASS Program
Authors: ZEITLER PHILIP , GALINDO RODOLFO J. , DAVIES MELANIE J. , BERGMAN BRANDON , THIEU VIVIAN , NICOLAY CLAUDIA , ALLEN SHERYL , LEE CLARE 
Published: June 2023

Young-onset T2D, defined as diagnosed before age 40, presents with a more aggressive disease course, faster beta-cell deterioration and reduced response to diabetes treatment compared to later-onset T2D. Tirzepatide (TZP), a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, was recently approved for the treatment of type 2 diabetes (T2D). This post-hoc analysis assessed the effect of tirzepatide on glycemic control, body weight (BW) and cardiometabolic markers in participants with young-onset T2D from the SURPASS program. Changes from baseline in mean HbA1c, BW, waist circumference (WC), and cardiometabolic markers including lipids, and blood pressure (BP) were compared in participants with young-onset (N=873, 20.5%) vs later-onset T2D (N=3394, 79.5%) at Week 40 (SURPASS-1, -2, -5) or Week 52 (SURPASS-3). No differential treatment effect was observed for participants with young- vs later-onset T2D. Tirzepatide treatment led to similar improvements in HbA1c and BW in both subgroups at Week 40/52 for all TZP doses (Figure). Furthermore, TZP (all doses) improved WC, lipids (triglycerides and HDL) and systolic BP similarly between the two groups. In conclusion, tirzepatide treatment led to similar improvements in HbA1c, BW and cardiometabolic markers (WC, lipids, SBP) in participants regardless of having young-onset or later-onset T2D.

Disclosure
P.Zeitler: Consultant; Eli Lilly and Company, Boehringer Ingelheim Inc., Johnson & Johnson. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. M.J.Davies: Advisory Panel; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Lexicon Pharmaceuticals, Inc., Pfizer Inc., Medtronic, ShouTi Pharma Inc., Consultant; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Research Support; AstraZeneca, Novo Nordisk, Sanofi-Aventis U.S., Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc., Speaker's Bureau; Lilly, Boehringer-Ingelheim, Novo Nordisk, AstraZeneca, Napp Pharmaceuticals Limited, Novartis, Sanofi. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. V.Thieu: None. C.Nicolay: Employee; Eli Lilly and Company. S.Allen: None. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

Funding
Eli Lilly and Company
783-P: Baseline HOMA2-B Can Predict Tirzepatide Efficacy—Post Hoc Analysis of the SURPASS-1 and SURPASS-2 Studies
Authors: HSIA STANLEY H. , THOMAS MELISSA K. , MATHIEU CHANTAL , WANG HUI , PELESHOK JENNIFER 
Published: June 2023

Tirzepatide (TZP) is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes (T2D). In the SURPASS-1 (S-1) (monotherapy) and SURPASS-2 (S-2) (on metformin) Phase 3 trials, TZP substantially reduced HbA1c and body weight (BW) in people with T2D. Exploratory post hoc analyses examined the predictive value of HOMA2-IR (insulin) and HOMA2-B (C-peptide) by quartiles low (lower beta-cell function or insulin resistance) [Q1] to high [Q4] for achieving HbA1c (&lt;5.7%, ≤6.5%) and BW reduction (≥10%, ≥15%) targets for those adherent to TZP treatment at Week 40. Odds ratios (OR) were calculated from logistic regression models using the overall mean as the reference. The results showed that TZP was equally likely to achieve BW and HbA1c targets in S-1 and S-2 regardless of baseline HOMA2-B and -IR quartiles, with the exception of S-2 where subjects with Q1 HOMA2-B (lowest beta-cell function) were significantly less likely and those with Q4 HOMA2-B (highest beta-cell function) were significantly more likely to reach HbA1c ≤6.5% (Figure). We conclude that baseline HOMA2-B, but not HOMA2-IR, may predict the likelihood of subjects achieving the HbA1c target ≤6.5% for patients enrolled in S-2 not controlled with metformin alone.

Disclosure
S.H.Hsia: Research Support; Eli Lilly and Company. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. C.Mathieu: Advisory Panel; Novo Nordisk A/S, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated, Roche Diabetes Care, Imcyse, Speaker's Bureau; Novo Nordisk A/S, AstraZeneca, Boehringer Ingelheim Inc., Eli Lilly and Company, Medtronic, Vertex Pharmaceuticals Incorporated. H.Wang: None. J.Peleshok: Employee; Eli Lilly and Company.

Funding
Eli Lilly and Company