Background: RGT-075 is a small-molecule oral GLP-1 receptor agonist (GLP1RA) in clinical development. RGT-075 (15-280 mg) was well-tolerated by healthy adults in a prior phase 1 single ascending dose study. Phase 1 multiple-ascending dose study of RGT-075 in adults with type 2 diabetes (T2DM) results are presented.

Methods: A Phase 1, randomized, double-blind, placebo-controlled, inpatient study planned multiple daily doses of RGT-075 or matching placebo (6 active/2 placebo per cohort) for up to 28 days in T2DM patients (baseline HbA1c 6-10.5% and concomitant metformin >500 mg/d) . An adaptive study design permitted dose and titration adjustments. Assessments included safety (primary) , PK, and exploratory efficacy changes in HbA1c, fasting plasma glucose (FPG) , continuous glucose monitoring time in range (CGM-TIR) , mixed-meal tolerance test MMTT, and body weight (BW) .

Results: Four Cohorts enrolled 36 patients (56%F/44%M; mean age 55yF/61yM) to receive ([Starting Dose]→[Titration Duration]→[Target Dose]) : Cohort 1 [60 mg][ no titration][60 mg]; Cohort 2 [30 mg][10 d][120 mg]; Cohort 3 [15 mg][20 d][180 mg]; Cohort 4 [15 mg][28 d][45 mg]. Adverse events (AEs) were reported by most subjects (100% C1 + C2; 88% C3; 83% C4; 78% pooled placebo) . Most AEs were of mild severity, drug-related for RGT-075 groups, and predominantly GI with no serious AEs or deaths. Baseline HbA1c was highly variable (7.2-9.0%) ; HbA1c mean changes from baseline ranged -0.6 to -1.2% across RGT-075 doses vs. -0.37% with placebo and correlated with FPG, CGM-TIR and MMTT results. BW mean change ranged -2.3 to -4.5 kg across RGT-075 doses vs -1.1 kg with placebo. RGT-075 plasma exposures increased as the dose levels increased.

Conclusion: RGT-075 GLP1RA oral small molecule (15-180 mg/day) up to 28 days was safe and QD dosing showed promising exploratory efficacy trends despite high baseline variability and short treatment duration.


M. A. Pirner: Employee; Regor Pharmaceuticals, Inc. J. Lin: None. F. Liu: Employee; Regor Pharmaceuticals Inc. L. Yao: None. M. E. Zettler: Employee; Cardinal Health, Regor Pharmaceuticals Inc. D. J. Valacer: Employee; Regor Pharmaceuticals, Inc.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at