In:
Diabetes, American Diabetes Association, Vol. 73, No. Supplement_1 ( 2024-06-14)
Abstract:
Introduction: T2D is characterized by fasting hyperglucagonemia and inappropriate meal suppression of glucagon, resulting in increased endogenous glucose production. While GRA is an attractive T2D target, previous programs have been discontinued due to nonclinical evidence of α-cell hyperplasia and increased blood pressure, LDL, and transaminases in clinical trials. ALP001E is a novel oral GRA with no evidence of these effects in extensive animal testing. ALP001E was well-tolerated in single- and multiple-dose clinical trials, with no significant changes in blood pressure, LDL, or liver enzymes. Objective: The objective of this trial was to assess pharmacodynamic effects of ALP001E in individuals with T2D. Methods: A placebo-controlled, double-blind, randomized controlled trial was conducted in 20 T2D patients administered 20, 40, or 80 mg ALP001E or placebo twice daily for 14 days. Results: Fasting glucose dose-dependently decreased 17-24% by day 2 (-1.50, -1.95, and -2.40 mmol/L for 20, 40, and 80 mg doses, p & lt;0.02) and remained suppressed throughout treatment; there was no significant change in the placebo group. Seven-point glucose dose-responsively decreased at all 7 points from baseline to day 14 for the ALP001E groups but not for placebo; the 80 mg dose group exhibited a 3.1 mmol/L (31.3%) decrease over all 7 points (p & lt;0.05). ALP001E treatment reduced HbA1c by ~5 mmol/L (~10%) across dose groups (p & lt;0.05). Insulin resistance (HOMA2-IR) decreased by 39% vs. placebo overall (p=0.017), with corresponding decreases in fasting insulin, while β-cell function (HOMA2-β) exhibited a marked dose-dependent increase (163% at the 80 mg dose, p & lt;0.05). Overall, ALP001E was safe and well-tolerated at all doses; all reported TEAEs were mild, with no dose discontinuation or dose-changes secondary to AEs. Conclusion: ALP001E has robust therapeutic potential for improving insulin resistance and glycemic control in patients with T2D. Disclosure C. Chung: Board Member; Alphala Group Inc. Caymen. S. Tseng: None. P. Chan: Employee; CMC Magnetics Corporation. G. Castro: None. Y. Chen: Employee; CMC Magnetics Corporation. C. Hsu: None. M.B. Zemel: Consultant; Enterin, TIXiMed, Glyscend Inc. Board Member; NuSirt. Consultant; Levicure, Seraxis, Aerami, Zealand Pharma A/S, Adipopharm.
Type of Medium:
Online Resource
ISSN:
0012-1797
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2024
detail.hit.zdb_id:
1501252-9
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