PMID- 38203742
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 1
DP  - 2024 Jan 1
TI  - New-Generation Glucokinase Activators: Potential Game-Changers in Type 2 Diabetes 
      Treatment.
LID - 10.3390/ijms25010571 [doi]
LID - 571
AB  - Achieving glycemic control and sustaining functional pancreatic beta-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 beta-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.
FAU - Haddad, Dania
AU  - Haddad D
AUID- ORCID: 0000-0001-6687-6361
AD  - Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Dsouza, Vanessa Sybil
AU  - Dsouza VS
AD  - Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Al-Mulla, Fahd
AU  - Al-Mulla F
AUID- ORCID: 0000-0001-5409-3829
AD  - Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Al Madhoun, Ashraf
AU  - Al Madhoun A
AUID- ORCID: 0000-0001-8593-3878
AD  - Genetics and Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
AD  - Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
LA  - eng
GR  - RA HM-2021-0001/Kuwait Foundation for the Advancement of Sciences/
PT  - Journal Article
PT  - Review
DEP - 20240101
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 2.7.1.2 (Glucokinase)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Glucokinase
MH  - Pancreas
MH  - Glycemic Control
MH  - *Drug-Related Side Effects and Adverse Reactions
PMC - PMC10779250
OTO - NOTNLM
OT  - TTP399
OT  - clinical trials
OT  - dorzagliatin
OT  - efficacy
OT  - glucokinase activator
OT  - safety
OT  - type 2 diabetes
COIS- The authors declare no conflict of interest.
EDAT- 2024/01/11 07:42
MHDA- 2024/01/12 06:42
PMCR- 2024/01/01
CRDT- 2024/01/11 01:20
PHST- 2023/11/23 00:00 [received]
PHST- 2023/12/28 00:00 [revised]
PHST- 2023/12/28 00:00 [accepted]
PHST- 2024/01/12 06:42 [medline]
PHST- 2024/01/11 07:42 [pubmed]
PHST- 2024/01/11 01:20 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - ijms25010571 [pii]
AID - ijms-25-00571 [pii]
AID - 10.3390/ijms25010571 [doi]
PST - epublish
SO  - Int J Mol Sci. 2024 Jan 1;25(1):571. doi: 10.3390/ijms25010571.