2833-LB: Utreglutide (GL0034) Shows Comparable Tolerability and Efficacy with Different Dose Escalation Regimens in Overweight and Obese Adults with Type 2 Diabetes (T2DM)

Introduction and Objective: We present interim data from a double-blind, placebo-controlled study investigating tolerability and efficacy of GL0034, a novel glucagon-like peptide-1 receptor agonist, in T2DM on metformin and/or an SGLT2-inhibitor. A symptom score was used to evaluate gastrointestinal adverse events (GI AEs). Methods: Participants were randomized to receive GL0034 once weekly in two different dose escalation regimens (table) or placebo over 16 weeks. Results: GL0034 was well tolerated with similar numbers of GI AEs with both dose escalation regimens, but a numerically higher symptom score in cohort 1 (Table). The incidence of all treatment-emergent AEs (TEAEs) was comparable between the cohorts. During the relatively short treatment period of 16 weeks, GL0034 significantly reduced body weight and improved glycemic control versus placebo as indicated by reductions in HbA1c, mean daily self-monitored plasma glucose (SMPG), peak glucose concentration after a liquid meal test and waist circumference. Efficacy results were not significantly different between the two GL0034 cohorts. Conclusion: GL0034 was well tolerated with two different dose-escalation regimens with maximum doses of 2.4 and 3.0 mg/week and led to pronounced improvements in body weight and glucose control in people with type 2 diabetes. Disclosure R. Thennati: Employee; Current; Sun Pharmaceutical Industries Ltd. G. Andersen: Consultant; Current; LaVita GmbH. V. Burade: Employee; Current; Sun Pharmaceutical Industries Ltd. T. Heise: Research Support; Ended; Afon Technology. Research Support; Current; Betagenon AB, Civica, Corteria Pharmaceuticals. Research Support; Ended; Cytoki Pharma. Research Support; Current; DioGenX, ENYO Pharma, Gan Current; Gan Current; Nanexa, Neodyne Biosciences, Sam Chun Dang. Research Support; Ended; Liom. Research Support; Current; Sun Pharmaceutical Industries Ltd., Zealand Pharma A/S. Other - Travel Grants; Current; Zealand Pharma A/S. Research Support; Current; AstraZeneca, Biocon, Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Research Support; Current; Novo Nordisk, Roche Diagnostics. Consultant; Current; i2o Therapeutics. Speaker's Bureau; Current; Novo Nordisk. R. Nagaraja: None. M. Natarajan: None. P. Shahi: None. B. Thorens: Advisory Panel; Current; Sun Pharmaceutical Industries Ltd. R. Pratley: Consultant; Current; Lilly USA LLC. Research Support; Current; National Institutes of Health, Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Novo Nordisk. Consultant; Current; Pfizer Inc., Recordati Rare Diseases Inc., Regeneron Pharmaceuticals Inc., Response Pharmaceuticals, Rona Therapeutics Ltd. Research Support; Current; Sanofi. Consultant; Current; Scholar Rock Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Sun Pharmaceutical Industries Ltd. Consultant; Current; Third Rock Ventures, Verdiva Bio Dev Limited. Research Support; Current; AstraZeneca AB, Boehringer Ingelheim International GmbH, Abbott Laboratories. Consultant; Current; Abbott Laboratories, AbbVie Inc. Other - Consulting; stock options; Current; Altanine, Inc. Consultant; Current; Amgen Inc., AstraZeneca Pharmaceuticals LP. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Bayer AG, Bayer HealthCare Pharmaceuticals Inc. Research Support; Current; Biomea Fusion. Consultant; Current; Boehringer Ingelheim Pharmaceuticals Inc., Carmot Therapeutics, Inc., Corcept Therapeutics. Research Support; Current; Dompé, Eli Lilly and Company. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Eli Lilly and Company. Research Support; Current; Endogenex Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Endogenex Inc. Consultant; Current; F. Hoffmann-La Roche Ltd. Research Support; Current; Fractyl Health, Inc. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Gasherbrum Bio Inc., Genprex. Consultant; Current; Hanmi Pharm. Co., Ltd. Other - Consulting: Thru 12/31/2023 payment directed to Dr. Pratley's employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Intas Pharmaceuticals Ltd. Research Support; Current; Lexicon Pharmaceuticals, Inc. Consultant; Current; Lexicon Pharmaceuticals, Inc. Speaker's Bureau; Current; Lilly USA LLC. M.A. Nauck: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Pfizer Inc., Regor. Consultant; Current; Structure Therapy. Speaker's Bureau; Current; Eli Lilly and Company, Novo Nordisk, Medscape, Medical Learning Institute. Advisory Panel; Current; Sun Pharmaceutical Industries Ltd.