HYPOTHESIS: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have distinct pathophysiologic etiologies. Therefore, therapeutic interventions designed to correct the specific underlying pathogenic abnormalities in IGT and IFG will be required to optimally prevent the progressive beta cell failure and development of overt type 2 diabetes.
SPECIFIC AIMS: 1. To examine the effect of the following pharmacologic interventions on beta cell function, insulin sensitivity, and glucose tolerance status in individuals with isolated impaired glucose tolerance (IGT): (i) treatment with the renal Sodium-glucose co-transporter 2 (SGLT2) inhibitor inhibitor, dapagliflozin; (ii) treatment with the inhibitors of dipeptidyl peptidase 4, also DPP4, saxagliptin ; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. 2. To examine the effect of the following pharmacologic interventions on beta cell function, insulin sensitivity, and glucose tolerance status in individuals with isolated impaired fasting glucose (IFG): (i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin. 3. To examine the effect of the following pharmacologic interventions on beta cell function, insulin sensitivity, and glucose tolerance status in individuals with combined impaired glucose tolerance (IGT) plus impaired fasting glucose (IFG): i) treatment with the renal SGLT2 inhibitor, dapagliflozin; (ii) treatment with the DPP4 inhibitor, saxagliptin; (iii) treatment with the thiazolidinedione, pioglitazone; (iv) treatment with the biguanide, metformin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
700
10mg/day
5mg/day
the dose will increase from 15 mg/day to 30 mg/day at month two
starting at 1000 mg/day and increased to 2000 mg/day at month 2.
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
RECRUITINGBeta cell function
Beta cell function will be measured as insulin secretion during the hyperglycemic clamp (mean plasma insulin concentration in uU/ml) multiplied by insulin sensitivity measured with the euglycemic insulin clamp (mg/kg.min).
Time frame: 24 months after treatment phase begins
Insulin sensitivity
Insulin sensitivity will be measured with the euglycemic insulin clamp and expressed as mg/kg.min.
Time frame: 24 months after treatment phase begins
Glucose tolerance status
Glucose tolerance status will be evaluated by measuring the HbA1c which is a measure of the average of the amount of glucose attached to hemoglobin over the past 3 months, expressed as a percentage.
Time frame: 24 months after treatment phase begins
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