Effects of Modulators of Gluconeogenesis, Glycogenolysis and Glucokinase Activity

Purpose

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

  • Type 2 Diabetes

Eligibility

Eligible Ages
Between 25 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Rita Basu
Birmingham, Alabama 35294
Contact:
Rita Basu, MD
507-269-3817
rbasu@uabmc.edu

More Details

Status
Recruiting
Sponsor
University of Alabama at Birmingham

Study Contact

Rita Basu, MD
2059341200
rbasu@uabmc.edu