Effects of Modulators of Gluconeogenesis, Glycogenolysis and Glucokinase Activity

Sponsor

University of Virginia (Other)

Overall Status

Recruiting

CT.gov ID

NCT05098470

Collaborator

(none)

100

Enrollment

Location

Arms

28.8

Anticipated Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

It has been shown that individuals with type 2 diabetes have higher blood sugar throughout the night than individuals without type 2 diabetes. However, it is still unknown if this rise in blood sugar can be controlled using medications.

This study will examine the effects of three different diabetes treatments to determine if they improve night time blood sugars. Participants will be randomly assigned for 8 weeks to one of the following three groups:

GROUP 1: Insulin. Participants will be instructed on self-injecting insulin glargine once-daily in the morning. The dose will be increased by the study team to avoid episodes of low blood sugar and to maintain fasting blood sugar concentrations between 70 to 180 mg/dl.

GROUP 2: Metformin. Participants will start the drug (500 mg twice daily) with meals. After 72 hours and in the absence of side effects, they will increase the dose to 500 mg with breakfast and 1,000 mg with supper. After a further 72 hours and in the absence of side effects, they will increase the dose to 1,000 mg twice daily with meals and continue until the end of the trial. The dose will be adjusted by the study team to maintain fasting blood sugar concentrations between 70 to 180 mg/dl.

GROUP 3: Dorzagliatin. This medication dose will be 75 mg twice daily. The investigators anticipate fasting glucose concentrations will be between 70 to 180 mg/dl since the dose of this medication cannot be titrated.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Metformin Drug: Insulin Glargine Drug: Dorzagliatin	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Effects of Modulators of Gluconeogenesis, Glycogenolysis and Glucokinase Activity on Endogenous Glucose Production in Type 2 Diabetes

Actual Study Start Date :

Mar 7, 2022

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jul 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metformin	Drug: Metformin 1500-2000 mg per day for 8 weeks
Active Comparator: Insulin Glargine	Drug: Insulin Glargine Long-acting insulin for 8 weeks
Experimental: Dorzagliatin	Drug: Dorzagliatin Oral Glucokinase Activator 75 mg twice daily for 8 weeks

Arm

Intervention/Treatment

Active Comparator: Metformin

Drug: Metformin

1500-2000 mg per day for 8 weeks

Active Comparator: Insulin Glargine

Drug: Insulin Glargine

Long-acting insulin for 8 weeks

Experimental: Dorzagliatin

Drug: Dorzagliatin

Oral Glucokinase Activator 75 mg twice daily for 8 weeks

Outcome Measures

Primary Outcome Measures

Contribution of gluconeogenesis (GNG) to endogenous glucose production (EGP) [8 weeks]
Ratio of GNG to total EGP

Secondary Outcome Measures

Contribution of glycogenolysis (GLY) to EGP [8 weeks]
Ratio of GLY to total EGP
Glucokinase activity [8 weeks]
UDP glucose flux

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

BMI:25-40 kg/m2.
HbA1C ≤ 9% on lifestyle therapy with or without monotherapy with metformin or sulphonylureas (SU); or combination therapies (metformin and SU, DPPIV inhibitors, only short acting GLP-1 analogues exenatide (Byeta) and liraglutide (Victoza).

Exclusion Criteria:

Insulin therapy
SGLT2 inhibitors
Long acting GLP-1 analogues
TZDs
Medications affecting GI motility (e.g., erythromycin, pramlintide).
Medications that may affect glucose metabolism such as corticosteroids, tricyclic-antidepressants, benzodiazepines, opiates, barbiturates, and anticoagulants.
Unstable diabetic retinopathy, microalbuminuria, macrovascular disease.
Upper GI disorder/surgery, debilitating chronic disease, anemia, and symptoms of undiagnosed illnesses.
History of alcoholism or substance abuse.
Pregnancy or breast feeding, or other comorbidities precluding participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rita Basu	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

University of Virginia

Investigators

None specified.

Study Documents (Full-Text)

Informed Consent Form - Nov 16, 2021

More Information

Publications

None provided.

Responsible Party:

Rita Basu, MD, Professor of Medicine, University of Virginia

ClinicalTrials.gov Identifier:

NCT05098470

Other Study ID Numbers:

DK029953

First Posted:

Oct 28, 2021

Last Update Posted:

Jul 21, 2022

Last Verified:

Jul 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2

Metformin

Insulin Glargine

Study Results

No Results Posted as of Jul 21, 2022