Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients With Prediabetes

• Sponsor: University of Guadalajara (Other)
• Overall Status: Completed
• CT.gov ID: NCT02700334
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 4
• Patients Per Site Per Month: 5.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prediabetes; Impaired Fasting Glucose; Impaired Glucose Tolerance	Drug: Dapagliflozin; Drug: Placebo	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients With Prediabetes
• Actual Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dapagliflozin Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks.	Drug: Dapagliflozin; 10 mg, one per day before breakfast during 12 weeks.; Other Names: Forxiga
Placebo Comparator: Placebo Placebo capsules, one per day before breakfast during 12 weeks.	Drug: Placebo; one per day before breakfast during 12 weeks.; Other Names: Calcined magnesium

Outcome Measures

Primary Outcome Measures

1. Fasting Glucose [Fasting Glucose levels at week 12]

   The fasting glucose levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12

2. Postprandial Glucose [Postprandial Glucose levels at Week 12]

   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

3. First Phase of Insulin Secretion [First Phase of Insulin Secretion at Week 12]

   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

4. Total Insulin Secretion [Total Insulin Secretion at Week 12]

   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

5. Insulin Sensitivity [Insulin Sensitivity at Week 12]

   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

6. Glycosylated Hemoglobin [Glycosylated Hemoglobin at Week 12]

   Glycosylated hemoglobin will be evaluated by ELISA and the entered values reflect the glycosylated hemoglobin at week 12

Secondary Outcome Measures

1. Body Weight [Body Weight at Week 12]

   The body weight will be measured with a bioimpedance balance and the entered values reflect the body weight at week 12

2. Body Mass Index [Body Mass Index at Week 12]

   Body Mas Index will be calculated with the Quetelet index formula and the entered values reflect the body mass index at week 12

3. Total Cholesterol [Total Cholesterol levels at Week 12]

   Total cholesterol levels will be evaluated by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12

4. Triglycerides [Triglycerides levels at Week 12]

   Triglycerides levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12

5. High Density Lipoprotein Cholesterol (HDL-c) [HDL-c levels at Week 12]

   HDL-c levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12

6. Alanine Aminotransferase (ALT) [ALT levels at Week 12]

   ALT levels will be evaluated with enzymatic/colorimetric techniques at week 12

7. Aspartate Aminotransferase (AST) [AST levels at Week 12]

   AST levels will be evaluated with enzymatic/colorimetric techniques at week 12

8. Creatinine [Creatinine levels at Week 12]

   Creatinine levels will be evaluated with enzymatic/colorimetric techniques at week 12

9. Uric Acid [Uric Acid levels at Week 12]

   Uric acid levels will be evaluated with enzymatic/colorimetric techniques at week 12

10. Systolic Blood Pressure [Systolic Blood Pressure at Week 12]

    Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12

11. Diastolic Blood Pressure [Diastolic Blood Pressure at Week 12]

    Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients both sexes

• Age between 30 and 60 years

• Diagnosis of prediabetes according ADA criteria (fasting blood glucose levels between 100-126 mg/dl; postprandial blood glucose levels after an oral glucose tolerance test with 75 of oral glucose between 140-199 mg/dl; or glycosylated hemoglobin between 5.7-6.4%)

• Informed consent signed

Exclusion Criteria:

• Women with confirmed or suspected pregnancy

• Women under lactation and/or puerperium

• Hypersensibility to ingredients of intervention

• Physical impossibility for taking pills

• Known uncontrolled renal, hepatic, heart or thyroid diseased

• Diabetes diagnosis

• Previous treatment for glucose

• Body Mass Index ≥35 kg/m2

• Triglycerides ≥500 mg/dL

• Total cholesterol ≥240 mg/dL

• Low density lipoprotein (c-LDL) ≥190 mg/dL

• Blood Pressure ≥140/90 mmHg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Intstituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara	Guadalajara	Jalisco	Mexico	44340

Sponsors and Collaborators

• University of Guadalajara

Investigators

• Principal Investigator: MANUEL GONZALEZ, PhD, University of Guadalajara

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Manuel González Ortiz, Researcher Professor, University of Guadalajara
• ClinicalTrials.gov Identifier: NCT02700334
• Other Study ID Numbers: DAPA-PREDIABETES
• First Posted: Mar 7, 2016
• Last Update Posted: Oct 28, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Manuel González Ortiz, Researcher Professor, University of Guadalajara: Prediabetes; Impaired fasting glucose; Hyperglycemia; Impaired glucose tolerance; Glucose intolerance; Dapagliflozin; Sodium glucose cotransporter 2 inhibitor; SGLT2
• Additional relevant MeSH terms: Insulin Resistance; Prediabetic State; Glucose Intolerance; Dapagliflozin

Study Results

Participant Flow

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dapagliflozin	Placebo	Total
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (6.3)	46.7 (9.8)	49.1 (8.05)
Sex: Female, Male (Count of Participants)
Female	9 75%	8 66.7%	17 70.8%
Male	3 25%	4 33.3%	7 29.2%
Region of Enrollment (participants) [Number]
Mexico	12 100%	12 100%	24 100%
Fasting Glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.9 (0.4)	6.0 (0.4)	6.0 (0.4)
Postprandial Glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.2 (1.4)	9.5 (1.4)	9.4 (1.4)
First Phase of Insulin Secretion (index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [index]	1126 (604)	1708 (709)	1417 (656.5)
Total Insulin Secretion (index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [index]	0.69 (0.31)	0.49 (0.17)	0.6 (0.2)
Insulin Sensitivity (index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [index]	1.78 (1.09)	1.94 (0.72)	1.9 (0.9)
Glycosylated Hemoglobin (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	5.8 (0.3)	5.8 (0.5)	5.8 (0.4)
Body Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	80.8 (16.3)	83.5 (8.2)	82.2 (12.3)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.3 (3.5)	33.0 (2.2)	31.7 (2.9)
Total Cholesterol (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.0 (0.9)	4.7 (0.6)	4.9 (0.8)
Triglycerides (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	1.5 (0.5)	1.4 (0.6)	1.5 (0.6)
High Density Lipoprotein cholesterol (HDL-c) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	1.6 (0.2)	1.5 (0.2)	1.6 (0.2)
Alanine Aminotransferase (ALT) (IU/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [IU/L]	33.3 (16.0)	37.1 (26.8)	35.2 (21.4)
Aspartate Aminotransferase (AST) (IU/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [IU/L]	36.0 (8.0)	32.7 (19.6)	34.4 (13.8)
Creatinine (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	0.06 (0.01)	0.07 (0.02)	0.07 (0.02)
Uric Acid (μmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μmol/L]	334 (70)	312 (101)	323 (85.5)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	124 (9)	126 (11)	125 (10)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	78 (10)	77 (11)	78 (11)

Outcome Measures

1. Primary Outcome

Title	Fasting Glucose
Description	The fasting glucose levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12
Time Frame	Fasting Glucose levels at week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [mmol/L]	5.1 (0.3)	5.9 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Postprandial Glucose
Description	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
Time Frame	Postprandial Glucose levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [mmol/L]	8.4 (1.5)	8.7 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.093
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	First Phase of Insulin Secretion
Description	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
Time Frame	First Phase of Insulin Secretion at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [index]	1096 (388)	1379 (566)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.878
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Total Insulin Secretion
Description	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
Time Frame	Total Insulin Secretion at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [index]	0.50 (0.18)	0.67 (0.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.959
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Insulin Sensitivity
Description	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
Time Frame	Insulin Sensitivity at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [index]	2.63 (1.04)	1.94 (0.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Glycosylated Hemoglobin
Description	Glycosylated hemoglobin will be evaluated by ELISA and the entered values reflect the glycosylated hemoglobin at week 12
Time Frame	Glycosylated Hemoglobin at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [percentage]	5.7 (0.3)	5.9 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.331
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Body Weight
Description	The body weight will be measured with a bioimpedance balance and the entered values reflect the body weight at week 12
Time Frame	Body Weight at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [kg]	77.8 (14.9)	82.5 (7.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Body Mass Index
Description	Body Mas Index will be calculated with the Quetelet index formula and the entered values reflect the body mass index at week 12
Time Frame	Body Mass Index at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [kg/m^2]	29.2 (3.1)	32.6 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Total Cholesterol
Description	Total cholesterol levels will be evaluated by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12
Time Frame	Total Cholesterol levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [mmol/L]	4.8 (0.9)	4.7 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.575
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Triglycerides
Description	Triglycerides levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12
Time Frame	Triglycerides levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [mmol/L]	1.5 (0.7)	1.6 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Secondary Outcome

Title	High Density Lipoprotein Cholesterol (HDL-c)
Description	HDL-c levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12
Time Frame	HDL-c levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [mmol/L]	1.5 (0.7)	1.6 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.721
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

12. Secondary Outcome

Title	Alanine Aminotransferase (ALT)
Description	ALT levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time Frame	ALT levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [IU/L]	29.3 (13.6)	27.7 (14.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

13. Secondary Outcome

Title	Aspartate Aminotransferase (AST)
Description	AST levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time Frame	AST levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [IU/L]	29.3 (13.6)	27.7 (14.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.333
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

14. Secondary Outcome

Title	Creatinine
Description	Creatinine levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time Frame	Creatinine levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [µmol/L]	79.6 (35.4)	61.9 (17.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.859
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

15. Secondary Outcome

Title	Uric Acid
Description	Uric acid levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time Frame	Uric Acid levels at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [µmol/L]	261.7 (59.5)	303.4 (83.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

16. Secondary Outcome

Title	Systolic Blood Pressure
Description	Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12
Time Frame	Systolic Blood Pressure at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [mmHg]	124 (12)	123 (12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.919
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

17. Secondary Outcome

Title	Diastolic Blood Pressure
Description	Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12
Time Frame	Diastolic Blood Pressure at Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.	Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
Measure Participants	12	12
Mean (Standard Deviation) [mmHg]	77 (10)	74 (10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.720
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse events were collected throughout the study (12 weeks)
Arm/Group Title	Dapagliflozin		Placebo
Arm/Group Description	Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks. Dapagliflozin: 10 mg, one per day before breakfast during 12 weeks.		Placebo capsules, one per day before breakfast during 12 weeks. Placebo: one per day before breakfast during 12 weeks.
All Cause Mortality
	Dapagliflozin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Dapagliflozin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Dapagliflozin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/12 (58.3%)		6/12 (50%)
Musculoskeletal and connective tissue disorders
Low back pain	1/12 (8.3%)	1	0/12 (0%)	0
Nervous system disorders
Headache	1/12 (8.3%)	1	3/12 (25%)	3
Dizziness	2/12 (16.7%)	2	2/12 (16.7%)	2
Renal and urinary disorders
Urinary tract infection	2/12 (16.7%)	2	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Edema in upper extremities	1/12 (8.3%)	1	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.