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Active, Not Recruiting

NCT Number: NCT05098470

Effects of Modulators of Gluconeogenesis, Glycogenolysis and Glucokinase Activity

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Age range

25 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Rita Basu, Birmingham, Alabama, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

metformin

Drug

1500-2000 mg per day for 8 weeks

insulin glargine

Drug

Long-acting insulin for 8 weeks

Dorzagliatin

Drug

Oral Glucokinase Activator 75 mg twice daily for 8 weeks

Primary outcomes

  1. Contribution of gluconeogenesis (GNG) to endogenous glucose production (EGP)

    Time frame: 8 weeks

    Ratio of GNG to total EGP

Secondary outcomes

  1. Contribution of glycogenolysis (GLY) to EGP

    Time frame: 8 weeks

    Ratio of GLY to total EGP

  2. Glucokinase activity

    Time frame: 8 weeks

    UDP glucose flux

Sponsors and collaborators

Lead sponsor

University of Alabama at Birmingham

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2025
Study completion
2026
First posted
Oct 28, 2021
Registry last updated
Jul 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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