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New-Generation Glucokinase Activators: Potential Game-Changers in Type 2 Diabetes Treatment.


ABSTRACT: Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA, TTP399, emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published preclinical studies and recent clinical trials.

SUBMITTER: Haddad D 

PROVIDER: S-EPMC10779250 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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New-Generation Glucokinase Activators: Potential Game-Changers in Type 2 Diabetes Treatment.

Haddad Dania D   Dsouza Vanessa Sybil VS   Al-Mulla Fahd F   Al Madhoun Ashraf A  

International journal of molecular sciences 20240101 1


Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pa  ...[more]

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