1218-OR: Efficacy and Safety of a Novel Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist (HDM1002) in Type 2 Diabetes Mellitus Patients Inadequately Controlled on Diet and Exercise or Metformin

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Introduction and Objective: HDM1002 is an oral small molecule GLP-1RA under development for the treatment of T2DM and obesity. This study evaluated the efficacy and safety of HDM1002 in Chinese adult with T2DM inadequately controlled on diet and exercise(D&E) or metformin(Met).Methods: In this randomized, double-blind phase 2 study, patients were randomized in a 1:1:1:1:1 ratio to receive HDM1002 50, 100, 200, 400mg QD, or placebo(PBO) for 12 weeks (12W). Doses were titrated weekly, starting at 50 mg QD. An additional open-label cohort with 26 pts explored the efficacy and safety of 400 mg administered as 200 mg BID, starting at 25 mg BID and titrated weekly. Primary endpoint was change from baseline in HbA1c at 12W.Results: Of 324 pts, all received study drug and 306(94.4%) completed treatment. At baseline, mean HbA1c was 8.5%, and 81.2% were inadequately controlled on Met. Least-squares (LS) mean changes in HbA1c for HDM1002 50, 100, 200, 400 mg QD and 200mg BID were -1.06%, -0.82%, -0.94%, -1.29% and -1.23%, respectively. All doses showed statistically significant reductions vs. placebo (P < 0.05). 12-week subgroup analysis: HDM1002 200/400 mg QD reduced HbA1c by 1.60/1.90% in D&E-failing pts and 0.76/1.11% in Met-failing pts. At 12W, the LS mean percentage change in BW reached -2.14kg for the 400 mg group vs. -0.78kg for PBO. At 12W, HDM1002 also showed reductions from baseline in FPG (up to -0.90 mmol/l) and 2h-PG (up to -6.64 mmol/l). Adverse events(AEs) were mostly mild or moderate gastrointestinal symptoms (nausea, vomiting, decreased appetite, diarrhoea). Only 7 pts discontinued treatment because of an AE and no serious AE was considered related to study drug.Conclusion: HDM1002 significantly reduced HbA1c in Chinese pts with T2DM inadequately controlled on D&E or Met. The safety profile supported further development of HDM1002 as an oral treatment option for T2DM.

Disclosure

Y. Mu: None. Q. Ni: None. Q. Li: None. J. Song: None. X. Shi: None. C. Meng: None. J. Li: None. D. Huang: None. Z. Song: None. H. Lu: Employee; Current; Huadong Medicine Co., Ltd. L. Shen: None. L. Zhong: Employee; Current; HuaDong Pharmaceutical Co., Ltd. J. Xu: Employee; Current; Huadong Medicine Co., Ltd. Stock/Shareholder; Current; Huadong Medicine Co., Ltd.



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