Effects of Dapagliflozin 10 mg on Insulin Resistance in Patients With Type 2 Diabetes Mellitus (DERISC)

• ClinicalTrials.gov Identifier: NCT02426541
• Recruitment Status: Completed
• First Posted: April 27, 2015
• Results First Posted: February 5, 2018
• Last Update Posted: February 5, 2018
• Sponsor: AstraZeneca
• Collaborators: Antaros Medical; Bioventure Hub; 43183 Mölndal; Sweden
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

This is an 8-week, single centre, randomized, parallel-group, double-blind, placebo-controlled Phase IV study to evaluate the effect of dapagliflozin on tissue specific insulin sensitivity in patients with Type 2 diabetes mellitus

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: Dapagliflozin; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: An 8-week, Single Centre, Randomized, Parallel-group, Double-blind, Placebo Controlled Phase IV Study to Evaluate Dapagliflozin 10 mg Once Daily Effects on Insulin Resistance in Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: March 23, 2015
• Actual Primary Completion Date: April 28, 2016
• Actual Study Completion Date: April 28, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dapagliflozin; Dapagliflozin Once Daily 10 mg	Drug: Dapagliflozin; Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks; Other Name: Forxiga, Farxiga
Placebo Comparator: Placebo; Matching placebo for Dapagliflozin Once Daily 10 mg	Drug: Placebo; Matching placebo to Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks

Outcome Measures

Primary Outcome Measures :

1. Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake [ Time Frame: From baseline to Week 8 ]
   Adjusted change from baseline in skeletal muscle insulin-stimulated gluocose uptake (umol/min/kg)

Secondary Outcome Measures :

1. Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake [ Time Frame: Baseline to Week 8 ]
   Change in adipose tissue insulin-stimulated glucose uptake assessed by hyperglycemic-euglycemic clamp using F-FDG PET
2. Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8 [ Time Frame: Baseline to Week 8 ]
   Adjusted change in liver insulin-stimulated glucose uptake assessed by hyperglycemic-euglycemic clamp using F-FDG PET

Eligibility Criteria

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

Criteria

Main Inclusion Criteria:

1. Provision of signed informed consent prior to any study specific procedures.
2. Female or male aged 35 to 70 years inclusive with suitable veins for cannulation or repeated venipuncture
3. Type 2 Diabetes mellitus defined as HbA1c of ≥ 6.5% and ≤ 10.5%.
4. Stable (≥ 3 months) T2D treatment with metformin and/or metformin+dipeptidyl peptidase-4 inhibitors (DPP-IV)
5. Body mass index (BMI) ≤ 40 kg/m2.

6. Female subjects must be of non-childbearing potential, meeting at least one of the following criteria:

   1. Hysterectomized females
   2. Postmenopausal women, defined as women who have not had a menstrual period within 1 year

Main Exclusion Criteria:

1. Any condition that is contraindicated with MRI such as, but not limited to, having a pacemaker or claustrophobia.
2. Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status.

3. Recent Cardiovascular Events in a patient:

   • Acute Coronary Syndrome (ACS) within 2 months prior to enrolment
   • Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment
   • Acute Stroke or Transient Ischemic Attack (TIA) within two months prior to enrolment
   • Less than two months post coronary artery revascularization
4. Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure.
5. Blood pressure at enrolment: Systolic BP ≥165 mm Hg and/or diastolic BP ≥100 mm Hg
6. Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of the first administration of the investigational product.
7. On insulin, GLP-1 or other oral antidiabetic drug treatment (metformin or both metformin and DPP-IV allowed) or using other medications known to affect glucose metabolism.

8. Any clinically significant abnormalities in physical examination, Electrocardiography (ECG) or clinical chemistry results as judged by the investigator. The following specific exclusion criteria apply to the selected Clinical Chemistry results:

   1. Creatinine clearance <60mL/min (estimated with Cockroft-Gault formula).
   2. Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN.
   3. Total bilirubin (TB) >2.0 mg/dL (34.2 µmol/L).
9. Body weight loss greater than 5% within 3 months prior to Visit 1.
10. Previous PET scan
11. History of or presence of (as found at Visit 1) any clinically significant disease, disorder or condition which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.

Contacts and Locations

Locations

Finland

Research Site

Turku, Finland

Sponsors and Collaborators

AstraZeneca

Antaros Medical

Bioventure Hub

43183 Mölndal

Sweden

Investigators

• Principal Investigator: Pirjo Nuutila, MD, PhD, Professor; Turku PET Centre, Turku, Finland

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Latva-Rasku A, Honka MJ, Kullberg J, Mononen N, Lehtimäki T, Saltevo J, Kirjavainen AK, Saunavaara V, Iozzo P, Johansson L, Oscarsson J, Hannukainen JC, Nuutila P. The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients. Diabetes Care. 2019 May;42(5):931-937. doi: 10.2337/dc18-1569. Epub 2019 Mar 18.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02426541
• Other Study ID Numbers: D1690C00025; 2014-005377-36 ( EudraCT Number )
• First Posted: April 27, 2015
• Results First Posted: February 5, 2018
• Last Update Posted: February 5, 2018
• Last Verified: July 2017

Keywords provided by AstraZeneca:

Diabetes Mellitus; Dapagliflozin; Placebo; Insulin resistance; Insulin sensitivity

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Dapagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs