Effects of Modulators of Gluconeogenesis, Glycogenolysis and Glucokinase Activity

NCT05098470 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 210395R01DK029953
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Contribution of gluconeogenesis (GNG) to endogenous glucose production (EGP)

  Ratio of GNG to total EGP

  8 weeks

Secondary Outcomes (2)

• Contribution of glycogenolysis (GLY) to EGP

  8 weeks

• Glucokinase activity

  8 weeks

Study Arms (3)

Metformin

ACTIVE COMPARATOR

Drug: Metformin

Insulin Glargine

ACTIVE COMPARATOR

Drug: Insulin Glargine

Dorzagliatin

EXPERIMENTAL

Drug: Dorzagliatin

Interventions

Metformin DRUG

1500-2000 mg per day for 8 weeks

Metformin

Insulin Glargine DRUG

Long-acting insulin for 8 weeks

Insulin Glargine

Dorzagliatin DRUG

Oral Glucokinase Activator 75 mg twice daily for 8 weeks

Dorzagliatin

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Rita Basu

Birmingham, Alabama, 35294, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Insulin Glargine; Dorzagliatin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: October 28, 2021
• Study Start: March 7, 2022
• Primary Completion: July 29, 2025
• Study Completion (Estimated): July 29, 2026
• Last Updated: July 30, 2025

Record last verified: 2025-07

Locations

US (2)