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

Metabolic Syndrome X Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02113241
• Other study ID #: DAPA-MS
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 2014
• Est. completion date: May 2015

Study information

• Verified date: October 2020
• Source: University of Guadalajara
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Insulin Resistance
• Metabolic Syndrome
• Metabolic Syndrome X
• Syndrome

Intervention

Drug:
• Dapagliflozin
Dapagliflozin capsules, 10 mg, one per day before breakfast during 90 days.
• Placebo
Placebo capsules, 10 mg, one per day before breakfast during 90 days.

Locations

Country	Name	City	State
Mexico	Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara	Guadalajara	Jalisco

Sponsors (1)

Lead Sponsor	Collaborator
University of Guadalajara

Country where clinical trial is conducted

Mexico, 

References & Publications (14)

Bolinder J, Ljunggren Ö, Johansson L, Wilding J, Langkilde AM, Sjöström CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189. Epub 2013 Aug 29. — View Citation

Bolinder J, Ljunggren Ö, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012 Mar;97(3):1020-31. doi: 10.1210/jc.2011-2260. Epub 2012 Jan 11. — View Citation

Chao EC. Dapagliflozin: an evidence-based review of its potential in the treatment of type-2 diabetes. Core Evid. 2012;7:21-8. doi: 10.2147/CE.S16359. Epub 2012 Jun 1. — View Citation

Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010 Oct;33(10):2217-24. doi: 10.2337/dc10-0612. Epub 2010 Jun 21. — View Citation

Kaku K, Inoue S, Matsuoka O, Kiyosue A, Azuma H, Hayashi N, Tokudome T, Langkilde AM, Parikh S. Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2013 May;15(5):432-40. doi: 10.1111/dom.12047. Epub 2013 Jan 25. — View Citation

Kasichayanula S, Liu X, Lacreta F, Griffen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. doi: 10.1007/s40262-013-0104-3. Review. — View Citation

Kasichayanula S, Liu X, Pe Benito M, Yao M, Pfister M, LaCreta FP, Humphreys WG, Boulton DW. The influence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus. Br J Clin Pharmacol. 2013 Sep;76(3):432-44. doi: 10.1111/bcp.12056. — View Citation

Kilov G, Leow S, Thomas M. SGLT2 inhibition with dapagliflozin -- a novel approach for the management of type 2 diabetes. Aust Fam Physician. 2013 Oct;42(10):706-10. Review. — View Citation

Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013 Sep;15(9):853-62. doi: 10.1111/dom.12127. Epub 2013 Jun 5. — View Citation

Merovci A, Solis-Herrera C, Daniele G, Eldor R, Fiorentino TV, Tripathy D, Xiong J, Perez Z, Norton L, Abdul-Ghani MA, DeFronzo RA. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014 Feb;124(2):509-14. doi: 10.1172/JCI70704. Epub 2014 Jan 27. Erratum in: J Clin Invest. 2014 May 1;124(5):2287. — View Citation

Obermeier M, Yao M, Khanna A, Koplowitz B, Zhu M, Li W, Komoroski B, Kasichayanula S, Discenza L, Washburn W, Meng W, Ellsworth BA, Whaley JM, Humphreys WG. In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos. 2010 Mar;38(3):405-14. doi: 10.1124/dmd.109.029165. Epub 2009 Dec 8. — View Citation

Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA(1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012 Jul;35(7):1473-8. doi: 10.2337/dc11-1693. Epub 2012 Mar 23. — View Citation

Yang L, Li H, Li H, Bui A, Chang M, Liu X, Kasichayanula S, Griffen SC, Lacreta FP, Boulton DW. Pharmacokinetic and pharmacodynamic properties of single- and multiple-dose of dapagliflozin, a selective inhibitor of SGLT2, in healthy Chinese subjects. Clin Ther. 2013 Aug;35(8):1211-1222.e2. doi: 10.1016/j.clinthera.2013.06.017. Epub 2013 Aug 2. — View Citation

Zhang L, Feng Y, List J, Kasichayanula S, Pfister M. Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight. Diabetes Obes Metab. 2010 Jun;12(6):510-6. doi: 10.1111/j.1463-1326.2010.01216.x. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Triglycerides Levels at Week 12.	The triglycerides levels are going to be evaluated at week 12 with enzymatic-colorimetric techniques.	Week 12
Primary	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
Primary	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
Primary	Systolic Blood Pressure at Week 12.	The systolic blood pressure is going to be evaluated at week 12 with a digital sphygmomanometer.	Week 12
Primary	Diastolic Blood Pressure at Week 12.	The diastolic blood pressure is going to be evaluated at week 12 with a digital sphygmomanometer.	Week 12
Primary	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 (?AUC insulin/?AUC glucose), the entered values reflect the total insulin secretion at week 12.	Week 12
Primary	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
Primary	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 / vglucose 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	Body Weight at Week 12.	The weight it's going to be measured at week 12 with a bioimpedance balance.	Week 12
Secondary	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
Secondary	Fat Mass at Week 12.	The fat mass is going to be evaluated at week 12 through bioimpedance.	Week 12
Secondary	Total Cholesterol at Week 12	The total cholesterol will be estimated by standardized techniques at week 12.	Week 12
Secondary	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
Secondary	Alanine Aminotransferase (ALT) at Week 12.	The ALT hepatic transaminase levels are going to be measured at week 12 with standardized techniques.	Week 12.
Secondary	Aspartate Aminotransferase (AST) at Week 12.	The hepatic transaminase AST will be evaluated with standardized methods at week 12	Week 12
Secondary	Creatinine at Week 12.	The creatinine levels are going to be measured at week 12 with standardized techniques.	Week 12.
Secondary	Uric Acid at Week 12.	The uric acid levels are going to be measured at week 12 with standardized techniques.	Week 12.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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