Evidence map›Paper›PMID 36342518›Full record

Trial reportDiabetes2023

Dorzagliatin, a Dual-Acting Glucokinase Activator, Increases Insulin Secretion and Glucose Sensitivity in Glucokinase Maturity-Onset Diabetes of the Young and Recent-Onset Type 2 Diabetes.

Elaine Chow, Ke Wang, Cadmon K P Lim, Sandra T F Tsoi, Baoqi Fan, Emily Poon, Andrea O Y Luk, Ronald C W Ma, Ele Ferrannini, Andrea Mari and 2 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 4 pooled it
8.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 4 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. Treatment Options for Patients with Maturity-Onset Diabetes of the Young (MODY): A Systematic Review of Literature: 2026 Update.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
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  6. Higher diabetes genetic load in proliferative diabetic retinopathy in South India: The South Indian GeNetics of DiAbeTic Retinopathy (SIGNATR) study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
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  17. Pediatric health, medicine and therapeutics · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Elaine ChowDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID 0000-0002-4147-3387
Ke WangDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Cadmon K P LimDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Sandra T F TsoiDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID 0000-0001-6129-379X
Baoqi FanDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Emily PoonDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
Andrea O Y LukDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID 0000-0002-5244-6069
Ronald C W MaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID 0000-0002-1227-803X
Ele FerranniniInstitute of Clinical Physiology, National Research Council of Italy (CNR), Pisa, Italy.ORCID 0000-0002-1384-1584
Andrea MariInstitute of Neuroscience, National Research Council of Italy (CNR), Padua, Italy.ORCID 0000-0002-1436-5591
Li ChenHua Medicine, Shanghai, China.ORCID 0000-0002-6192-3752
Juliana C N ChanDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.ORCID 0000-0003-1325-1194
Chinese University of Hong Kong · HKHua Medicine (China) · CNIstituto di Fisiologia Clinica · ITNational Research Council · IT

Funding

Hua Medicine Investigator Initiated Study 2020.231RGC Research Impact Fund R4012-18
6 · The paper itself

Abstract

Glucokinase (GK, gene symbol GCK) maturity-onset diabetes of the young (MODY) is caused by heterozygous inactivating mutations in GK and impaired glucose sensing. We investigated effects of dorzagliatin, a novel allosteric GK activator, on insulin secretion rates (ISRs) and β-cell glucose sensitivity (βCGS) in GCK-MODY and recent-onset type 2 diabetes. In a double-blind, randomized, crossover study, 8 participants with GCK-MODY and 10 participants with type 2 diabetes underwent 2-h 12 mmol/L hyperglycemic clamps following a single oral dose of dorzagliatin 75 mg or matched placebo. Effects of dorzagliatin on wild-type and mutant GK enzyme activity were investigated using an NADP+-coupled assay with glucose-6-phosphate dehydrogenase in vitro. In GCK-MODY, dorzagliatin significantly increased absolute and incremental second-phase ISRs versus placebo but not the acute insulin response. Dorzagliatin improved βCGS in GCK-MODY with an upward and leftward shift in ISR-glucose response. Dorzagliatin increased basal ISRs in type 2 diabetes, with smaller changes in second-phase ISRs versus GCK-MODY. In vitro, dorzagliatin directly reduced the glucose half saturation concentration of wild-type GK and selected GK mutants to varying degrees. Dorzagliatin directly restored enzyme activity of select GK mutants and enhanced wild-type GK activity, thereby correcting the primary defect of glucose sensing in GCK-MODY.

Indexed as

Diabetes Mellitus, Type 2Cross-Over StudiesGlucokinaseGlucoseHumansInsulin SecretionMutationPyrazolesDorzagliatinGlucokinaseGlucosePyrazoles

Identifiers

PMID36342518
PMCPMC9871194
OpenAlexW4308372893

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.