Diabetes Mellitus, Type 2NCT02969798
Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)
A study testing Dapagliflozin, Saxagliptin and Pioglitazone in people with Diabetes Mellitus, Type 2 and Impaired Glucose Tolerance (IGT), run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2, Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG)
- What is being tested?
- Dapagliflozin, Saxagliptin and Pioglitazone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 700 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2014to Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- NGT subjects will serve as controls and will be matched in age, gender, ethnicity, and BMI to IGT and IFG subjects
- Male or female subjects between the ages of 18 and 65 years of age, inclusive, at Screening.
- FPG < 100 mg/dl and 2-h PG < 140 mg/dl
- BMI = 24-40 kg/m2;
- Stable body weight (±4lbs) over the preceding 3 months
- Subjects with no evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
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- Females of childbearing potential with a negative pregnancy test at Screening and Treatment visits, using one of the following forms of contraception for the duration of participation in the study (i.e., until Follow-up 7-14 days post last dose):
- Oral contraceptive
- Injectable progesterone
- Subdermal implant
- Spermicidal foam/gel/film/cream/suppository
- Diaphragm with spermicide
- Copper or hormonal containing IUD
- Sterile male partner vasectomized > 6 month pre-dosing.
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
- Subjects must be willing and able to comply with scheduled visits, treatment, laboratory tests and study procedures.
Who cannot join
- Recent (i.e., within three (3) months prior to Screening) evidence or medical history of unstable concurrent disease such as: documented evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, immunological, or clinically significant neurological disease.
- Subjects with a family history of diabetes in a first degree relative
- BMI of less than 24 or greater than 40 kg/m2
- Unstable body weight (change of greater than ±4lbs over the preceding 3 months
- Subjects participating in an excessively heavy exercise program
- Subject with a feeding/sleeping schedule different from a daytime feeding/night time sleeping schedule
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- Subjects taking medications known to alter glucose metabolism (with the exception of metformin and/or pioglitazone) or which effect brain neurosynaptic function are excluded.
- Subjects with evidence of major organ system disease as determined by physical exam, history, and screening laboratory data
- Pregnant subjects or subjects unwilling to use birth control during their study enrollment
- Blood donation of approximately 1 pint (500 mL) within 8 weeks prior to Screening.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
- Subjects with hematuria will be excluded.
- Subjects with evidence or prior history of heart failure will be excluded
- Subjects with family history of pancreatic, bladder, and breast cancer will be excluded.
- Subjects with history of pancreatitis will be excluded.
- Subjects with eGFR < 60 ±5 ml/min.1.73m2 will be excluded.
- Subjects with elevated serum creatinine (>1.5 mg/dl males/1.4 mg/dl females) will be excluded.
- Subjects with a history of orthostatic hypotension (>15/10 mmHg) will be excluded.
- Subjects with liver enzymes (ALT, AST) >3-fold above upper normal limit will be excluded.
- Subjects with a history of hypersensitivity to pioglitazone, dapagliflozin, or Saxagliptin will be excluded.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Ralph A DeFronzo, MD, 210-567-6691, defronzo@uthscsa.edu
Monica Palomo, BS, 210-567-6710, palomom@uthscsa.edu
About this study
Official title: Preservation of Beta Cell Function in Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)
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.
Read the detailed description
SPECIFIC AIMS:
- 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.
- 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.
- 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.
- Conditions
- Diabetes Mellitus, Type 2, Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG)
- Being tested
- Dapagliflozin, Saxagliptin, Pioglitazone, Metformin
- Medical subject headings
- Diabetes Mellitus, Type 2, Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called farxiga
10mg/day
SaxagliptinDrug
Also called onglyza
5mg/day
PioglitazoneDrug
Also called actos
the dose will increase from 15 mg/day to 30 mg/day at month two
MetforminDrug
Also called glucophage
starting at 1000 mg/day and increased to 2000 mg/day at month 2.
| Study group | Role | What they receive |
|---|---|---|
| Healthy normal glucose tolerance (NGT) subjects | No intervention | Subjects (Fasting Plasma Glucose or FPG < 100 mg/dl and 2-h PG < 140 mg/dl) without FH (family history) of diabetes in a first degree relative |
| Isolated IGT with Dapagliflozin | Active comparator | Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive dapagliflozin, 10 mg/day Receives: Drug: Dapagliflozin |
| Isolated IGT with Saxagliptin | Active comparator | Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive saxagliptin, 5 mg/day Receives: Drug: Saxagliptin |
| Isolated IGT with Pioglitazone | Active comparator | Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two Receives: Drug: Pioglitazone |
| Isolated IGT with Metformin | Active comparator | Healthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2. Receives: Drug: Metformin |
| Isolated IFG with Dapagliflozin | Active comparator | Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive dapagloflozin, 10mg/day Receives: Drug: Dapagliflozin |
| Isolated IFG with Saxagliptin | Active comparator | Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive saxagliptin, 10mg/day Receives: Drug: Saxagliptin |
| Isolated IFG with Pioglitazone | Active comparator | Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two Receives: Drug: Pioglitazone |
| Isolated IFG with Metformin | Active comparator | Healthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2. Receives: Drug: Metformin |
| IGT plus IFG with Dapagliflozin | Active comparator | Healthy subjects with IGT plus IFG will receive dapagliflozin, 10mg/day Receives: Drug: Dapagliflozin |
| IGT plus IFG with Saxagliptin | Active comparator | Healthy subjects with IGT plus IFG will receive saxagliptin, 10mg/day Receives: Drug: Saxagliptin |
| IGT plus IFG with Pioglitazone | Active comparator | Healthy subjects with IGT plus IFG will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two Receives: Drug: Pioglitazone |
| IGT plus IFG with Metformin | Active comparator | Healthy subjects with IGT plus IFG will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Beta 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).
Measured: 24 months after treatment phase begins
Insulin sensitivity
Insulin sensitivity will be measured with the euglycemic insulin clamp and expressed as mg/kg.min.
Measured: 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.
Measured: 24 months after treatment phase begins
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2016 (estimated)
- Study start1 Jan 2014
- Primary completion28 Feb 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- American Diabetes Association, AstraZeneca, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Ralph A DeFronzo, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02969798
- Sponsor's protocol ID
- HSC20130414H
- Other IDs
- R01DK024092-34
- Status last verified
- Sep 2026
- First submitted
- 16 Mar 2016
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preservation of Beta Cell Function in Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)
- ClinicalTrials.gov ID
- NCT02969798
- Acronym / sponsor ID
- HSC20130414H
- Conditions
- Diabetes Mellitus, Type 2, Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- American Diabetes Association, AstraZeneca, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Jan 2014 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 21 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
SPECIFIC AIMS:
- 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.
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Healthy normal glucose tolerance (NGT) subjects | No intervention | –Subjects (Fasting Plasma Glucose or FPG < 100 mg/dl and 2-h PG < 140 mg/dl) without FH (family history) of diabetes in a first degree relative |
| Isolated IGT with Dapagliflozin | Active comparator | Drug: DapagliflozinHealthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive dapagliflozin, 10 mg/day |
| Isolated IGT with Saxagliptin | Active comparator | Drug: SaxagliptinHealthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive saxagliptin, 5 mg/day |
| Isolated IGT with Pioglitazone | Active comparator | Drug: PioglitazoneHealthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two |
| Isolated IGT with Metformin | Active comparator | Drug: MetforminHealthy subjects with isolated IGT (FPG < 100; 2-h PG = 140-199) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2. |
| Isolated IFG with Dapagliflozin | Active comparator | Drug: DapagliflozinHealthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive dapagloflozin, 10mg/day |
| Isolated IFG with Saxagliptin | Active comparator | Drug: SaxagliptinHealthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive saxagliptin, 10mg/day |
| Isolated IFG with Pioglitazone | Active comparator | Drug: PioglitazoneHealthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two |
| Isolated IFG with Metformin | Active comparator | Drug: MetforminHealthy subjects with isolated IFG (FPG = 100-125; 2-h PG < 140) will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2. |
| IGT plus IFG with Dapagliflozin | Active comparator | Drug: DapagliflozinHealthy subjects with IGT plus IFG will receive dapagliflozin, 10mg/day |
| IGT plus IFG with Saxagliptin | Active comparator | Drug: SaxagliptinHealthy subjects with IGT plus IFG will receive saxagliptin, 10mg/day |
| IGT plus IFG with Pioglitazone | Active comparator | Drug: PioglitazoneHealthy subjects with IGT plus IFG will receive pioglitazone, the dose will increase from 15 mg/day to 30 mg/day at month two |
| IGT plus IFG with Metformin | Active comparator | Drug: MetforminHealthy subjects with IGT plus IFG will receive Metformin, starting at 1000 mg/day and increased to 2000 mg/day at month 2. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- NGT subjects will serve as controls and will be matched in age, gender, ethnicity, and BMI to IGT and IFG subjects
Key exclusion criteria (20 listed)
- Recent (i.e., within three (3) months prior to Screening) evidence or medical history of unstable concurrent disease such as: documented evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, immunological, or clinically significant neurological disease.
- Subjects with a family history of diabetes in a first degree relative
- BMI of less than 24 or greater than 40 kg/m2
- Unstable body weight (change of greater than ±4lbs over the preceding 3 months
- Subjects participating in an excessively heavy exercise program
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DapagliflozinAlso: farxiga10mg/day | Drug | IGT plus IFG with Dapagliflozin, Isolated IFG with Dapagliflozin, Isolated IGT with Dapagliflozin |
| SaxagliptinAlso: onglyza5mg/day | Drug | IGT plus IFG with Saxagliptin, Isolated IFG with Saxagliptin, Isolated IGT with Saxagliptin |
| PioglitazoneAlso: actosthe dose will increase from 15 mg/day to 30 mg/day at month two | Drug | IGT plus IFG with Pioglitazone, Isolated IFG with Pioglitazone, Isolated IGT with Pioglitazone |
| MetforminAlso: glucophagestarting at 1000 mg/day and increased to 2000 mg/day at month 2. | Drug | IGT plus IFG with Metformin, Isolated IFG with Metformin, Isolated IGT with Metformin |
Primary outcome
Beta cell function
Time frame: 24 months after treatment phase begins
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).
Insulin sensitivity
Time frame: 24 months after treatment phase begins
Insulin sensitivity will be measured with the euglycemic insulin clamp and expressed as mg/kg.min.
Glucose tolerance status
Time frame: 24 months after treatment phase begins
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ralph A DeFronzo, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dapagliflozin, Saxagliptin and Pioglitazone in people with Diabetes Mellitus, Type 2 and Impaired Glucose Tolerance (IGT), run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ralph A DeFronzo, MD (210-567-6691, defronzo@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Beta cell function (time frame: 24 months after treatment phase begins). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.