Effect of Dapagliflozin Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion

Study Overview
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Brief Summary
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The Metabolic Syndrome is a high prevalence disease worldwide. About a quarter of the adult population suffers the disease. Dapagliflozin is an inhibitor of the sodium-glucose co-transporter SGLT2 in the kidney and is a novel treatment for diabetes type 2. Some studies indicate that SGLT2 inhibitors have benefits on blood pressure, triglycerides levels and help to raise the levels of high density lipoproteins cholesterol (c-HDL). The aim of this study is to evaluate the effect of dapagliflozin on metabolic syndrome, insulin sensitivity and insulin secretion. The investigators hypothesis is that the administration of dapagliflozin modifies the metabolic syndrome, insulin sensitivity and insulin secretion.

Detailed Description
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A randomized, double-blind, placebo-controlled clinical trial its going to carry out in 24 patients with a diagnosis of metabolic syndrome in accordance with the International Diabetes Federation (IDF). Waist circumference, glucose, insulin levels, lipid profile, creatinine and acid uric are going to be load after a 75 g of dextrose load. 12 patients will receive Forxiga (dapagliflozin), 10 mg, one per day before breakfast during 3 months. The remaining 12 patients will receive placebo at the same dose. 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. Results will be presented as mean and standard deviation. Intra and inter group differences are going to be tested using the Wilcoxon signed-rank and Mann-Whitney U-test respectively; p≤0.05 it's going to be considered significant.

Official Title
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Effect of Dapagliflozin Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion

Conditions
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Metabolic Syndrome X

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients both sexes Age between 30 and 60 years Metabolic Syndrome according to the IDF criteria Waist circumference Man ≥90 cm Woman ≥80 cm And two of the following criteria High density lipoprotein Man ≤40 mg/dL Woman ≤50 mg/dL Fasting glucose ≥100 mg/dL Triglycerides ≥150 mg/dL Blood pressure ≥130/85 mmHg Informed consent signed Exclusion Criteria: Women with confirmed or suspected pregnancy Women under lactation and/or puerperium Hypersensibility to SGLT2 inhibitors Physical impossibility for taking pills Known uncontrolled renal, hepatic, heart or thyroid diseased Previous treatment for the metabolic syndrome components Body Mass Index ≥39.9 kg/m2 Fasting glucose ≥126 mg/dL Triglycerides ≥500 mg/dL Total cholesterol ≥240 mg/dL Low density lipoprotein (c-LDL) ≥190 mg/dL Blood Pressure ≥140/90 mmHg

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Dapagliflozin capsules, 10 mg, one per day before breakfast during 90 days. | Drug: Dapagliflozin<br>* Dapagliflozin capsules, 10 mg, one per day before breakfast during 90 days.<br>* Other names: Forxiga;|
| Placebo Comparator: Placebo<br>Placebo capsules, 10 mg, one per day before breakfast during 90 days. | Drug: Placebo<br>* Placebo capsules, 10 mg, one per day before breakfast during 90 days.<br>* Other names: Calcined magnesium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist Circumference at Week 12. | The waist circumference is going to be evaluated at week 12 with a flexible tape with standardized techniques. | Week 12 | 
| Triglycerides Levels at Week 12. | The triglycerides levels are going to be evaluated at week 12 with enzymatic-colorimetric techniques. | Week 12 | 
| High Density Lipoprotein (c-HDL) Levels at Week 12. | The c-HDL levels are going to be evaluated at week 12 with enzymatic/colorimetric techniques. | Week 12 | 
| Glucose Levels at Minute 0 at Week 12. | The fasting glucose (0') levels are going to be evaluated at week 12 with enzymatic/colorimetric techniques. | Week 12 | 
| Systolic Blood Pressure at Week 12. | The systolic blood pressure is going to be evaluated at week 12 with a digital sphygmomanometer. | Week 12 | 
| Diastolic Blood Pressure at Week 12. | The diastolic blood pressure is going to be evaluated at week 12 with a digital sphygmomanometer. | Week 12 | 
| Insulinogenic Index (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 (ΔAUC insulin/ΔAUC glucose), the entered values reflect the total insulin secretion at week 12. | Week 12 | 
| Stumvoll Index (First 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 frst phase of insulin secretion at week 12. | Week 12 | 
| Matsuda Index (Total 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 at week 12. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Weight at Week 12. | The weight it's going to be measured at week 12 with a bioimpedance balance. | Week 12 | 
| Body Mass Index at Week 12 | The Body Mass index it's going to be calculated at week 12 with the Quetelet index. | Week 12 | 
| Fat Mass at Week 12. | The fat mass is going to be evaluated at week 12 through bioimpedance. | Week 12 | 
| Total Cholesterol at Week 12 | The total cholesterol will be estimated by standardized techniques at week 12. | Week 12 | 
| Low Density Lipoproteins (c-LDL) at Week 12 | The c-LDL levels are going to be measured at week 12 with standardized techniques. | Week 12 | 
| Alanine Aminotransferase (ALT) at Week 12. | The ALT hepatic transaminase levels are going to be measured at week 12 with standardized techniques. | Week 12. | 
| Aspartate Aminotransferase (AST) at Week 12. | The hepatic transaminase AST will be evaluated with standardized methods at week 12 | Week 12 | 
| Creatinine at Week 12. | The creatinine levels are going to be measured at week 12 with standardized techniques. | Week 12. | 
| Uric Acid at Week 12. | The uric acid levels are going to be measured at week 12 with standardized techniques. | Week 12. | 
| AUC of Glucose at Week 12. | The AUC of glucose will be calculated from the glucose values obtained from the minuted oral glucose tolerance curve at week 12 | Week 12 | 
| AUC of Insulin at Week 12. | The AUC will be calculated from the insulin values obtained from the minuted oral glucose tolerance curve at week 12 | Week 12 | 
| Glucose at Minute 30 at Week 12. | The glucose at minute 30 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve | Week 12 | 
| Glucose at Minute 60 at Week 12. | The glucose at minute 60 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve | Week 12 | 
| Glucose at Minute 90 at Week 12. | The glucose at minute 90 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve | Week 12 | 
| Glucose at Minute 120 at Week 12. | The glucose at minute 120 is going to be evaluated at week 12 during a minuted oral glucose tolerance curve | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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forxiga, metabolic syndrome, dapagliflozin, insulin secretion, insulin sensitivity