Evaluation of the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type 2 Diabetes - Full Text View

Purpose

This study is being carried out to see if dapagliflozin in addition to metformin decreases body weight and if so, how it compares with metformin alone.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Dapagliflozin Drug: Metformin Drug: Sitagliptin Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A 24-week,Multi-centre,Int.,Double-blind,Rand.,Parallel-group,Plac.-Controlled,Phase III Study With a 78-week Ext.Per. to Evaluate the Effect of Dapagliflozin in Combination With Metformin on Body Weight in Subjects With Type2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Alone

Resource links provided by NLM:

MedlinePlus related topics: Body Weight Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride Dapagliflozin Sitagliptin

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Adjusted Mean Change in Total Body Weight [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
To evaluate the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin on total body weight after 24 weeks of oral administration of double-blind treatment.

Secondary Outcome Measures:

Adjusted Mean Change in Waist Circumference [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on waist circumference.
Adjusted Mean Change in Body Fat Mass [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on total body fat mass measured by dual energy X-ray absorptiometry.
Proportion of Participants With Body Weight Decrease ≥5% [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 24 weeks of double-blind treatment on body weight decrease ≥5%. Least Squares Mean represents the percent of participants adjusted for body weight baseline value.

Other Outcome Measures:

Adjusted Percent Change in Bone Mineral Density (BMD) at Lumbar Spine (L1-4) [ Time Frame: Baseline to Week 102 ] [ Designated as safety issue: Yes ]
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at lumbar spine (L1-4) as measured by Dual Energy X-ray Absorptiometry.
Adjusted Percent Change in Bone Mineral Density (BMD) at Femoral Neck [ Time Frame: Baseline to Week 102 ] [ Designated as safety issue: Yes ]
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at femoral neck as measured by Dual Energy X-ray Absorptiometry.
Adjusted Percent Change in Bone Mineral Density (BMD) at Total Hip [ Time Frame: Baseline to Week 102 ] [ Designated as safety issue: Yes ]
To assess the effect of dapagliflozin 10 mg daily in combination with metformin compared to placebo in combination with metformin after 102 weeks of double-blind treatment on Bone Mineral Density at total hip as measured by Dual Energy X-ray Absorptiometry.


Enrollment:	182
Study Start Date:	February 2009
Study Completion Date:	December 2011
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A Dapagliflozin 10 mg plus Metformin	Drug: Dapagliflozin Tablet oral 10 mg total daily dose once daily 102 weeks Drug: Metformin Tablet oral 1500 - 2500 mg total daily dose 1-3 times a day104 weeks Drug: Sitagliptin Tablet oral 100 mg total daily dose once daily rescue medication
Placebo Comparator: B Placebo plus Metformin	Drug: Metformin Tablet oral 1500 - 2500 mg total daily dose 1-3 times a day104 weeks Drug: Sitagliptin Tablet oral 100 mg total daily dose once daily rescue medication Drug: Placebo Matching placebo for dapagliflozin, tablet, oral, once daily, 102 weeks

Eligibility


Ages Eligible for Study:	30 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Type 2 diabetes
Ongoing treatment with metformin on a stable dose of ≥1500 mg/day for at least 12 weeks prior to enrolment
Inadequate glycemic control, defined as HbA1c ≥6.5% and ≤8.5%
≥30 years for males
≥55 years for females

Exclusion Criteria:

Type 1 Diabetes
Body weight change >5% within 3 months prior to enrolment
Renal and liver impairment

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00855166

Locations


Bulgaria
Research Site
Blagoevgrad, Bulgaria
Research Site
Sofia, Bulgaria
Czech Republic
Research Site
Beroun, Czech Republic
Research Site
Brno, Czech Republic
Research Site
Praha, Czech Republic
Research Site
Semily, Czech Republic
Research Site
Slany, Czech Republic
Hungary
Research Site
Balatonfured, Hungary
Research Site
Budapest, Hungary
Research Site
Csongrad, Hungary
Research Site
Kecskemet, Hungary
Research Site
TAT, Hungary
Poland
Research Site
Elblag, Poland
Research Site
Krakow, Poland
Research Site
Torun, Poland
Sweden
Research Site
Goteborg, Sweden
Research Site
Jarfalla, Sweden
Research Site
Lund, Sweden
Research Site
Malmo, Sweden
Research Site
Stockholm, Sweden
Research Site
Uppsala, Sweden

Sponsors and Collaborators

AstraZeneca

Bristol-Myers Squibb

Investigators


Principal Investigator:	Jan Bolinder, MD, PhD	Dept of Endocrinology, Metabolism and Diabetes Karolinska University Hospital Huddinge Karolinska Institutet 141 86 Stockholm Sweden

More Information

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

Bolinder J, Ljunggren Ö, Johansson L, Wilding J, Langkilde AM, Sjöström CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189. Epub 2013 Aug 29.

Ljunggren Ö, Bolinder J, Johansson L, Wilding J, Langkilde AM, Sjöström CD, Sugg J, Parikh S. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab. 2012 Nov;14(11):990-9. doi: 10.1111/j.1463-1326.2012.01630.x. Epub 2012 Jun 29.


Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00855166 History of Changes
Other Study ID Numbers:	D1690C00012
Study First Received:	March 3, 2009
Results First Received:	January 21, 2013
Last Updated:	August 9, 2013
Health Authority:	Bulgaria: Bulgarian Drug Agency Czech Republic: State Institute for Drug Control Hungary: National Institute of Pharmacy Poland: Ministry of Health Sweden: Medical Products Agency

Keywords provided by AstraZeneca:


Dapagliflozin Metformin Type 2 diabetes body weight

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Body Weight Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Signs and Symptoms Metformin Sitagliptin Phosphate	Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016