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

NCT02113241 | Completed Phase 2 Results

• 1 other identifier: DAPA-MS
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metabolic Syndrome X

Keywords

metabolic syndrome; forxiga; dapagliflozin; insulin secretion; insulin sensitivity

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (15)

• Body Weight at Week 12.

  Week 12

• Body Mass Index at Week 12

  Week 12

• Fat Mass at Week 12.

  Week 12

• Total Cholesterol at Week 12

  Week 12

• Low Density Lipoproteins (c-LDL) at Week 12

  Week 12

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin capsules, 10 mg, one per day before breakfast during 90 days.

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Placebo capsules, 10 mg, one per day before breakfast during 90 days.

Drug: Placebo

Interventions

Dapagliflozin DRUG

Dapagliflozin capsules, 10 mg, one per day before breakfast during 90 days.

Also known as: Forxiga

Dapagliflozin

Placebo DRUG

Placebo capsules, 10 mg, one per day before breakfast during 90 days.

Also known as: Calcined magnesium

Placebo

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Guadalajara: lead

Study Sites (1)

Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara

Guadalajara, Jalisco, 44340, Mexico

Location

Related Publications (14)

• Bolinder J, Ljunggren O, 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.

  PMID: 22238392 BACKGROUND

• 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.

  PMID: 22446170 BACKGROUND

• 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.

  PMID: 22701099 BACKGROUND

• 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.

  PMID: 24105299 BACKGROUND

• 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.

  PMID: 23910664 BACKGROUND

• 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.

  PMID: 19996149 BACKGROUND

• 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.

  PMID: 23210765 BACKGROUND

• 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.

  PMID: 24130972 BACKGROUND

• 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.

  PMID: 23194084 BACKGROUND

• 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.

  PMID: 20518806 BACKGROUND

• 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.

  PMID: 23668478 BACKGROUND

• 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.

  PMID: 20566676 BACKGROUND

• Bolinder J, Ljunggren O, Johansson L, Wilding J, Langkilde AM, Sjostrom 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.

  PMID: 23906445 BACKGROUND

• 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.

  PMID: 24463448 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Insulin Resistance

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: DR. MANUEL GONZALEZ ORTIZ
• Organization: INSTITUTO DE TERAPEUTICA EXPERIMENTAL Y CLINICA, UNIVERSITY OF GUADALAJARA

uiec@prodigy.net.mx

+52 3310585200

Study Officials

• MANUEL GONZALEZ, PhD

  University of Guadalajara

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 14, 2014
• Study Start: April 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: October 28, 2020
• Results First Posted: October 8, 2020

Record last verified: 2020-10

Locations

ME (1)