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149-LB: The MetAP2 Inhibitor, ZGN-1061, Improves Insulin Sensitivity and Beta-Cell Function in Patients with Type 2 Diabetes.
- Source :
- Diabetes; 2019 Supplement, Vol. 68, pN.PAG-N.PAG, 1p
- Publication Year :
- 2019
-
Abstract
- ZGN-1061 is a second-generation methionine aminopeptidase 2 (MetAP2) inhibitor in development for treatment of T2D. Full results of a Phase 2 clinical trial of ZGN-1061 vs. placebo (PBO) administered SC for 12 weeks on change from baseline in A1C in subjects with T2D are reported elsewhere. Baseline (ITT population N=175) A1C 8.6±1.1%, BMI 37±7 kg/m<superscript>2</superscript>, T2D duration 8±6 y. ZGN-1061 was generally well tolerated; 93% completed the trial. LS mean±SE A1C change was 0.2±0.1% for PBO vs. ±0.4±0.1% and -0.9±0.2% for 0.9 and 1.8 mg ZGN-1061 (both p<0.001 vs. PBO). PBO weight change was -0.6±0.3 kg vs. -1.4±0.3 kg (p=ns) and ±2.8±0.5 kg (p<0.001) for 0.9 and 1.8 mg ZGN-1061. This analysis included a subset of subjects who participated in a mixed-meal tolerance test (MMTT) at baseline and week 12. ZGN-1061 produced dose-dependent improvements in fasting and postprandial glucose (p<0.05 vs. PBO). Minimal model analysis showed improvements in insulin sensitivity (S<subscript>I</subscript>) and disposition index (DI_OB; a measure of β-cell compensation) from baseline to week 12 with ZGN-1061 (Table). In an exploratory combined analysis of 0.9+1.8 mg ZGN-1061, S<subscript>I</subscript> and DI_OB increased (p=0.02 and p=0.07). S<subscript>I</subscript> and DI_OB were unchanged with PBO. In patients with T2D, improved glycemic control with ZGN-1061 may be driven by changes in insulin sensitivity and β-cell function. These results support future assessments using other definitive methods. Disclosure: R. Fabunmi: None. R.N. Bergman: Consultant; Self; Zafgen, Inc. F. Piccinini: None. T. Kim: Employee; Spouse/Partner; Celgene Corporation. Employee; Self; Zafgen, Inc. D. Zhuang: Employee; Self; Zafgen, Inc. K. Taylor: Employee; Self; Zafgen, Inc. D.D. Kim: Employee; Self; Zafgen, Inc. Funding: Zafgen, Inc. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 68
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 152327205
- Full Text :
- https://doi.org/10.2337/db19-149-LB