Effects of Dapagliflozin on Insulin Resistance and Insulin Secretion in Subjects With Type 2 Diabetes

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Trial to Evaluate the Effects of Dapagliflozin on Insulin Resistance and Insulin Secretion in Subjects With Type 2 Diabetes

The purpose of this study is to evaluate the effects of dapagliflozin on insulin sensitivity

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University General Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with type 2 diabetes and inadequate glycemic control, defined as A1C ≥ 7.0 and ≤ 10.0% at the enrollment visit
• Subjects should have been receiving either metformin therapy OR metformin therapy AND one insulin secretagogue for at least 12 weeks prior to enrollment
• C-peptide ≥ 1.0 ng/ml (0.34 nmol/l)
• BMI ≤ 45.0 kg/m2

Exclusion Criteria:

• Urine albumin to creatinine ratio (UACR) > 1,800 mg/g (203.4 mg/mmol/Cr)
• Aspartate Aminotransferase (AST) > 3X Upper limit of normal (ULN)
• Alanine aminotransferase (ALT) > 3X ULN
• Serum Total Bilirubin > 2 mg/dL (34.2 μmol/l)
• Serum Creatinine (Scr) ≥ 1.50 mg/dL (133 μmol/l) for men; SCr ≥ 1.40 mg/dL (124 μmol/l) for women
• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Tablets, Oral, 0 mg, Once daily, 12 weeks
Experimental: Dapagliflozin	Drug: Dapagliflozin; Tablets, Oral, 5 mg, once daily, 12 weeks; Other Names: BMS-512148

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Percent Change From Baseline in Insulin Sensitivity at Week 12 (Last Observation Carried Forward [LOCF])	Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.	From Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Insulin Secretion at Week 12 (Last Observation Carried Forward [LOCF])	Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during the randomization visit and Week 12 in the double-blind period.	From Baseline to Week 12

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Astra Zeneca, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• Publication

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: January 28, 2009
• First Submitted That Met QC Criteria: January 28, 2009
• First Posted (Estimate): January 29, 2009

Study Record Updates

• Last Update Posted (Actual): April 24, 2017
• Last Update Submitted That Met QC Criteria: March 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: MB102-045

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No