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Prediabetes is a term that refers to alterations in glucose homeostasis, including impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both, involving a higher risk of progression type 2 diabetes mellitus (T2DM).
Dapagliflozin is a selective and reversible inhibitor of sodium-glucose type 2 (SGLT-2) co-transporter, which reduces renal glucose reabsorption and promotes the glucose excretion through urine, so that the blood glucose is improved in patients with T2DM. Although this mechanism is independent of insulin, there are evidence of improved secretion and insulin sensitivity, so it is interesting to assess these effects in patients with prediabetes, as potential therapy for treating such disorders and prevent progression to T2DM.
The aim of this study is to evaluate the effect of Dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes.
The investigators hypothesis is that the administration of dapagliflozin improve insulin secretion and insulin sensitivity in patients with prediabetes.
A randomized, double-blind, placebo-controlled clinical trial in 24 patients with a diagnosis of prediabetes in accordance with the American Diabetes Association (ADA) without treatment.
They will be assigned randomly two groups of 12 patients each to receive 10 mg of Dapagliflozin (Forxiga, Astra Zeneca) or placebo, one per day before breakfast during 12 weeks.
There will be calculated Area Under the Curve of glucose and insulin, total insulin secretion (Insulinogenic index), first-phase of insulin secretion (Stumvoll index) and insulin sensitivity (Matsuda index).
This protocol it's already approved by the local ethics committee and written informed consent it's going to be obtained from all volunteers.
Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p ≤0.05.
This protocol was approved by a local ethics committee and written informed consent will be obtained from all volunteers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dapagliflozin | Experimental | Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. |
|
| Placebo | Placebo Comparator | Placebo capsules, one per day before breakfast during 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin | Drug | 10 mg, one per day before breakfast during 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Fasting Glucose | The fasting glucose levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12 | Fasting Glucose levels at week 12 |
| Postprandial Glucose | Postprandial glucose will be evaluated after a oral glucose tolerance test with enzymatic/colorimetric techniques and the entered values reflect the insulin sensitivity at week 12 | Postprandial Glucose levels at Week 12 |
| First Phase of Insulin Secretion | The first phase of insulin secretion will be calculated with Stumvoll index and the entered values reflect the frst phase of insulin secretion at week 12. Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. First phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'), the entered values reflect the first phase of insulin secretion | First Phase of Insulin Secretion at Week 12 |
| Total Insulin Secretion | Total insulin secretion will be calculated with insulinogenic index and the entered values reflect the total insulin secretion at week 12. The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus. Total insulin secretion was calculated with the insulinogenic index (ΔABC insulin/ΔABC glucose), the entered values reflect the total insulin secretion | Total Insulin Secretion at Week 12 |
| Insulin Sensitivity | Insulin sensitivity will be calculated with Matsuda index and the entered values reflect the insulin sensitivity at week 12. Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index [10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)]. The entered values reflect the insulin sensitivity |
| Measure | Description | Time Frame |
|---|---|---|
| Body Weight | The body weight will be measured with a bioimpedance balance and the entered values reflect the body weight at week 12 | Body Weight at Week 12 |
| Body Mass Index | Body Mas Index will be calculated with the Quetelet index formula and the entered values reflect the body mass index at week 12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MANUEL GONZALEZ, PhD | University of Guadalajara | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Intstituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara | Guadalajara | Jalisco | 44340 | Mexico |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dapagliflozin | Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks. |
| FG001 | Placebo | Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dapagliflozin | Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Fasting Glucose | The fasting glucose levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12 | Posted | Mean | Standard Deviation | mmol/L | Fasting Glucose levels at week 12 |
|
Adverse events were collected throughout the study (12 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dapagliflozin | Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| DR. MANUEL GONZALEZ ORTIZ | INSTITUTO DE TERAPUTICA EXPERIMENTAL Y CLINICA, UNIVERSITY OF GUADALAJARA | +52 3310585200 | 34212 | uiec@prodigy.net.mx |
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| ID | Term |
|---|---|
| D011236 | Prediabetic State |
| D018149 | Glucose Intolerance |
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C529054 | dapagliflozin |
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| Placebo | Drug | one per day before breakfast during 12 weeks. |
|
|
| Insulin Sensitivity at Week 12 |
| Glycosylated Hemoglobin | Glycosylated hemoglobin will be evaluated by ELISA and the entered values reflect the glycosylated hemoglobin at week 12 | Glycosylated Hemoglobin at Week 12 |
| Body Mass Index at Week 12 |
| Total Cholesterol | Total cholesterol levels will be evaluated by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12 | Total Cholesterol levels at Week 12 |
| Triglycerides | Triglycerides levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12 | Triglycerides levels at Week 12 |
| High Density Lipoprotein Cholesterol (HDL-c) | HDL-c levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12 | HDL-c levels at Week 12 |
| Alanine Aminotransferase (ALT) | ALT levels will be evaluated with enzymatic/colorimetric techniques at week 12 | ALT levels at Week 12 |
| Aspartate Aminotransferase (AST) | AST levels will be evaluated with enzymatic/colorimetric techniques at week 12 | AST levels at Week 12 |
| Creatinine | Creatinine levels will be evaluated with enzymatic/colorimetric techniques at week 12 | Creatinine levels at Week 12 |
| Uric Acid | Uric acid levels will be evaluated with enzymatic/colorimetric techniques at week 12 | Uric Acid levels at Week 12 |
| Systolic Blood Pressure | Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12 | Systolic Blood Pressure at Week 12 |
| Diastolic Blood Pressure | Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12 | Diastolic Blood Pressure at Week 12 |
Placebo capsules, one per day before breakfast during 12 weeks.
Placebo: one per day before breakfast during 12 weeks.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Fasting Glucose | Mean | Standard Deviation | mmol/L |
|
| Postprandial Glucose | Mean | Standard Deviation | mmol/L |
|
| First Phase of Insulin Secretion | Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. First phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'), the entered values reflect the first phase of insulin secretion | Mean | Standard Deviation | index |
|
| Total Insulin Secretion | The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus. Total insulin secretion was calculated with the insulinogenic index (ΔABC insulin/ΔABC glucose), the entered values reflect the total insulin secretion | Mean | Standard Deviation | index |
|
| Insulin Sensitivity | Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index [10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)]. The entered values reflect the insulin sensitivity | Mean | Standard Deviation | index |
|
| Glycosylated Hemoglobin | Mean | Standard Deviation | percentage |
|
| Body Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| Total Cholesterol | Mean | Standard Deviation | mmol/L |
|
| Triglycerides | Mean | Standard Deviation | mmol/L |
|
| High Density Lipoprotein cholesterol (HDL-c) | Mean | Standard Deviation | mmol/L |
|
| Alanine Aminotransferase (ALT) | Mean | Standard Deviation | IU/L |
|
| Aspartate Aminotransferase (AST) | Mean | Standard Deviation | IU/L |
|
| Creatinine | Mean | Standard Deviation | mmol/L |
|
| Uric Acid | Mean | Standard Deviation | μmol/L |
|
| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Primary | Postprandial Glucose | Postprandial glucose will be evaluated after a oral glucose tolerance test with enzymatic/colorimetric techniques and the entered values reflect the insulin sensitivity at week 12 | Posted | Mean | Standard Deviation | mmol/L | Postprandial Glucose levels at Week 12 |
|
|
|
|
| Primary | First Phase of Insulin Secretion | The first phase of insulin secretion will be calculated with Stumvoll index and the entered values reflect the frst phase of insulin secretion at week 12. Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. First phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'), the entered values reflect the first phase of insulin secretion | Posted | Mean | Standard Deviation | index | First Phase of Insulin Secretion at Week 12 |
|
|
|
|
| Primary | Total Insulin Secretion | Total insulin secretion will be calculated with insulinogenic index and the entered values reflect the total insulin secretion at week 12. The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus. Total insulin secretion was calculated with the insulinogenic index (ΔABC insulin/ΔABC glucose), the entered values reflect the total insulin secretion | Posted | Mean | Standard Deviation | index | Total Insulin Secretion at Week 12 |
|
|
|
|
| Primary | Insulin Sensitivity | Insulin sensitivity will be calculated with Matsuda index and the entered values reflect the insulin sensitivity at week 12. Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index [10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)]. The entered values reflect the insulin sensitivity | Posted | Mean | Standard Deviation | index | Insulin Sensitivity at Week 12 |
|
|
|
|
| Primary | Glycosylated Hemoglobin | Glycosylated hemoglobin will be evaluated by ELISA and the entered values reflect the glycosylated hemoglobin at week 12 | Posted | Mean | Standard Deviation | percentage | Glycosylated Hemoglobin at Week 12 |
|
|
|
|
| Secondary | Body Weight | The body weight will be measured with a bioimpedance balance and the entered values reflect the body weight at week 12 | Posted | Mean | Standard Deviation | kg | Body Weight at Week 12 |
|
|
|
|
| Secondary | Body Mass Index | Body Mas Index will be calculated with the Quetelet index formula and the entered values reflect the body mass index at week 12 | Posted | Mean | Standard Deviation | kg/m^2 | Body Mass Index at Week 12 |
|
|
|
|
| Secondary | Total Cholesterol | Total cholesterol levels will be evaluated by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12 | Posted | Mean | Standard Deviation | mmol/L | Total Cholesterol levels at Week 12 |
|
|
|
|
| Secondary | Triglycerides | Triglycerides levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12 | Posted | Mean | Standard Deviation | mmol/L | Triglycerides levels at Week 12 |
|
|
|
|
| Secondary | High Density Lipoprotein Cholesterol (HDL-c) | HDL-c levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12 | Posted | Mean | Standard Deviation | mmol/L | HDL-c levels at Week 12 |
|
|
|
|
| Secondary | Alanine Aminotransferase (ALT) | ALT levels will be evaluated with enzymatic/colorimetric techniques at week 12 | Posted | Mean | Standard Deviation | IU/L | ALT levels at Week 12 |
|
|
|
|
| Secondary | Aspartate Aminotransferase (AST) | AST levels will be evaluated with enzymatic/colorimetric techniques at week 12 | Posted | Mean | Standard Deviation | IU/L | AST levels at Week 12 |
|
|
|
|
| Secondary | Creatinine | Creatinine levels will be evaluated with enzymatic/colorimetric techniques at week 12 | Posted | Mean | Standard Deviation | µmol/L | Creatinine levels at Week 12 |
|
|
|
|
| Secondary | Uric Acid | Uric acid levels will be evaluated with enzymatic/colorimetric techniques at week 12 | Posted | Mean | Standard Deviation | µmol/L | Uric Acid levels at Week 12 |
|
|
|
|
| Secondary | Systolic Blood Pressure | Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12 | Posted | Mean | Standard Deviation | mmHg | Systolic Blood Pressure at Week 12 |
|
|
|
|
| Secondary | Diastolic Blood Pressure | Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12 | Posted | Mean | Standard Deviation | mmHg | Diastolic Blood Pressure at Week 12 |
|
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 7 |
| 12 |
| EG001 | Placebo | Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks. | 0 | 12 | 0 | 12 | 6 | 12 |
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Edema in upper extremities | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | Systematic Assessment |
|
| Low back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |