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

NCT02700334 | Completed Phase 4 Results

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

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.

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

Outcome Measures

Primary Outcomes (6)

• Fasting Glucose

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

  Fasting Glucose levels at week 12

• Postprandial Glucose

  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

  Postprandial Glucose levels at Week 12

• First Phase of Insulin Secretion

  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

  First Phase of Insulin Secretion at Week 12

• Total Insulin Secretion

  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

  Total Insulin Secretion at Week 12

• Insulin Sensitivity

  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

  Insulin Sensitivity at Week 12

• Glycosylated Hemoglobin

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

  Glycosylated Hemoglobin at Week 12

Secondary Outcomes (11)

• Body Weight

  Body Weight at Week 12

• Body Mass Index

  Body Mass Index at Week 12

• Total Cholesterol

  Total Cholesterol levels at Week 12

• Triglycerides

  Triglycerides levels at Week 12

• High Density Lipoprotein Cholesterol (HDL-c)

  HDL-c levels at Week 12

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks.

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Placebo capsules, one per day before breakfast during 12 weeks.

Drug: Placebo

Interventions

Dapagliflozin DRUG

10 mg, one per day before breakfast during 12 weeks.

Also known as: Forxiga

Dapagliflozin

Placebo DRUG

one per day before breakfast during 12 weeks.

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Guadalajara: lead

Study Sites (1)

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

Guadalajara, Jalisco, 44340, Mexico

Location

MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance; Hyperglycemia

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: DR. MANUEL GONZALEZ ORTIZ
• Organization: INSTITUTO DE TERAPUTICA 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 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher Professor

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: March 7, 2016
• Study Start: October 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: February 1, 2017
• Last Updated: October 28, 2020
• Results First Posted: October 8, 2020

Record last verified: 2020-10

Locations

ME (1)