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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of dapagliflozin on insulin sensitivity

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |