Dorzagliatin for glucokinase (GCK-MODY) diabetes

Evaluating a Novel, Allosteric Glucokinase Activator in Monogenic Diabetes Secondary to Inactivating Glucokinase Mutations: a Randomised, Cross-over Trial

This trial will test whether dorzagliatin, a drug that activates glucokinase, can lower blood sugar in adults with GCK-MODY caused by an inactivating GCK mutation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years to 74 Years
• Sex: All
• Sponsor: Chinese University of Hong Kong (Academic / other)
• Locations: 1 site (Hong Kong)
• Trial ID: NCT06976658 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled cross-over trial enrolling adults who are heterozygous for pathogenic or likely pathogenic GCK mutations and have mild fasting hyperglycemia. Participants receive dorzagliatin and matched placebo in separate treatment periods with washout between periods to compare within-person glucose responses. Key eligibility includes age 18–74, BMI 18–30 kg/m2, fasting plasma glucose >5.6 mmol/L, and adequate renal and hepatic function. Major exclusions are pregnancy, recent cardiovascular events, severe renal or hepatic dysfunction, recent severe hypoglycaemia, or substance misuse.

Who should consider this trial

Good fit: Adults aged 18–74 who are heterozygous carriers of a pathogenic or likely pathogenic GCK mutation, have BMI 18–30 kg/m2, fasting plasma glucose >5.6 mmol/L, and meet organ function and safety criteria are the intended candidates.

Not a fit: People without GCK mutations, those with severe renal or hepatic dysfunction, pregnancy or recent cardiovascular events, or those with recent severe hypoglycaemia are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, dorzagliatin could lower fasting glucose and improve day-to-day glycemic control in people with GCK-MODY, potentially reducing the need for other glucose-lowering measures in this group.

How similar studies have performed: Some glucokinase activators have lowered glucose in type 2 diabetes but showed mixed durability and safety signals, and targeted trials in GCK-MODY are limited, so this application is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 and \<75 years
2. body mass index (BMI) \>18 and \<30 kg/m2
3. fasting plasma glucose \>5.6 mmol/L at screening
4. Participants with GCK-MODY had and are heterozygous carriers of a pathogenic or likely pathogenic GCK mutation at screening based on guidelines published by the American College of Medical Genetics and Genomics (ACMG), Association for Clinical Genomic Science (ACGS) and the ClinGen Monogenic Diabetes Expert Panel (MDEP) .

Exclusion Criteria:

1. Body weight \<45kg at screening
2. Current or planning pregnancy or lactating
3. troke or cardiovascular disease within 6 months of recruitment
4. severe renal dysfunction (estimated glomerular filtration rate \<30mL/min/1.73m2 or renal replacement therapy)
5. severe hepatic dysfunction (aspartate transaminase and/or alanine transaminase \> 3 times upper limit of normal)
6. history of drug abuse or excessive alcohol intake
7. severe hypoglycemia within 6 months prior to screening
8. anaemia with Hb \<10 g/dL at screening
9. excessive blood loss \>300mL within 1 month of screening
10. use of strong or moderate CYP3A4 inhibitors or inducers
11. use of sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, sodium glucose transporter 2 inhibitors, insulin, thiazolidinediones, acarbose in the 6 weeks prior to randomisation
12. use of long-term high-dose corticosteroids at randomisation
13. serious concurrent infections at time of screening

Where this trial is running

Hong Kong

• 3M, Diabetes and Endocrine Research Center — Hong Kong, Hong Kong (Recruiting)

Study contacts

• Study coordinator: Elaine Chow, MD

Conditions Diabetes Mellitus; Monogenic Diabetes; GCK-MODY; glucokinase activator