Clinical trial NCT02700334: Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients With Prediabetes
Official title: Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients With Prediabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prediabetes
Impaired Fasting Glucose
Impaired Glucose Tolerance
Keywords: Prediabetes
Impaired fasting glucose
Hyperglycemia
Impaired glucose tolerance
Glucose intolerance
Dapagliflozin
Sodium glucose cotransporter 2 inhibitor
SGLT2
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2016-03-07
Enrollment: 24
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fasting Glucose
timeFrame: Fasting Glucose levels at week 12
measure: Postprandial Glucose
timeFrame: Postprandial Glucose levels at Week 12
measure: First Phase of Insulin Secretion
timeFrame: First Phase of Insulin Secretion at Week 12
measure: Total Insulin Secretion
timeFrame: Total Insulin Secretion at Week 12
measure: Insulin Sensitivity
timeFrame: Insulin Sensitivity at Week 12
measure: Glycosylated Hemoglobin
timeFrame: Glycosylated Hemoglobin at Week 12
Secondary outcomes:
measure: Body Weight
timeFrame: Body Weight at Week 12
measure: Body Mass Index
timeFrame: Body Mass Index at Week 12
measure: Total Cholesterol
timeFrame: Total Cholesterol levels at Week 12
measure: Triglycerides
timeFrame: Triglycerides levels at Week 12
measure: High Density Lipoprotein Cholesterol (HDL-c)
timeFrame: HDL-c levels at Week 12
measure: Alanine Aminotransferase (ALT)
timeFrame: ALT levels at Week 12
measure: Aspartate Aminotransferase (AST)
timeFrame: AST levels at Week 12
measure: Creatinine
timeFrame: Creatinine levels at Week 12
measure: Uric Acid
timeFrame: Uric Acid levels at Week 12
measure: Systolic Blood Pressure
timeFrame: Systolic Blood Pressure at Week 12
measure: Diastolic Blood Pressure
timeFrame: Diastolic Blood Pressure at Week 12
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: Intstituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: MANUEL GONZALEZ, PhD
role: PRINCIPAL_INVESTIGATOR
References: