Efficacy and Safety of Dapagliflozin in Combination With Metformin in Type 2 Diabetes Patients

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00660907
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 1,217
• Locations: 77
• Arms: 2
• Duration (Months): 58.1
• Patients Per Site: 15.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study is being carried out to see if dapagliflozin as an addition to metformin is effective and safe in treating patients with type 2 diabetes when compared to glipizide (sulphonylurea) as an addition to metformin treatment.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: dapagliflozin; Drug: glipizide; Drug: metformin hydrochloride	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1217 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 52-Week International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 156-Week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin in Combination With Metformin Compared With Sulphonylurea in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy Alone.
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 dapagliflozin plus metformin	Drug: dapagliflozin; Tablet oral 2.5, 5, or 10 mg total daily dose once daily 208 weeks; Drug: metformin hydrochloride; Tablet oral 1500, 2000, or 2500 mg total daily dose split/twice daily 218 weeks; Other Names: Glucophage
Active Comparator: 2 glipizide plus metformin	Drug: glipizide; Capsule oral 5, 10, or 20 mg total daily dose once or split/twice daily 208 weeks; Other Names: Glucotrol ; Drug: metformin hydrochloride; Tablet oral 1500, 2000, or 2500 mg total daily dose split/twice daily 218 weeks; Other Names: Glucophage

Outcome Measures

Primary Outcome Measures

1. Adjusted Mean Change in HbA1c Levels [Baseline to Week 52]

   To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on the absolute change from baseline in HbA1c level after 52 weeks double-blind treatment in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone.

Secondary Outcome Measures

1. Adjusted Mean Change in Body Weight [Baseline to Week 52]

   To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight after 52 weeks double-blind treatment.

2. Proportion of Participants With at Least One Episode of Hypoglycemia [Baseline to Week 52]

   To assess the effect of dapagliflozin plus metformin treatment compared to glipizide plus metformin on the occurrence of hypoglycemic events. Least Squares Mean represents the percent of participants adjusted for HbA1c baseline value.

3. Proportion of Participants With Body Weight Reduction of at Least 5% [Baseline to Week 52]

   To evaluate the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight assessed by a reduction after 52 weeks of at least 5% compared to baseline. Least Squares Mean represents the percent of participants adjusted for baseline value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 Diabetes

• Treated with oral anti-diabetic drug therapy therapy including Metformin for at least 8 weeks prior to enrolment

• HbA1c >6.5% and </=10%

Exclusion Criteria:

• Type 1 Diabetes

• Insulin therapy within one year of enrolment

• Renal (kidney) failure or dysfunction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Buenos Aires		Argentina
2	Research Site	Caba		Argentina
3	Research Site	Capital Federal		Argentina
4	Research Site	Ciudad de Buenos Aires		Argentina
5	Research Site	Corrientes		Argentina
6	Research Site	Córdoba		Argentina
7	Research Site	La Plata		Argentina
8	Research Site	Rosario		Argentina
9	Research Site	Santa Fe		Argentina
10	Research Site	L'aigle		France
11	Research Site	Murs Erigne		France
12	Research Site	Nantes Cedex 1		France
13	Research Site	Nantes		France
14	Research Site	Paris		France
15	Research Site	Tours		France
16	Research Site	Vannes		France
17	Research Site	Bad Lauterberg		Germany
18	Research Site	Berlin		Germany
19	Research Site	Dresden		Germany
20	Research Site	Essen		Germany
21	Research Site	Frankfurt		Germany
22	Research Site	Hamburg		Germany
23	Research Site	Heilbronn		Germany
24	Research Site	Ludwigshafen		Germany
25	Research Site	Mainz		Germany
26	Research Site	Pirna		Germany
27	Research Site	Schmiedeberg		Germany
28	Research Site	Wangen		Germany
29	Research Site	Perugia		Italy
30	Research Site	Pisa		Italy
31	Research Site	Roma		Italy
32	Research Site	Acapulco		Mexico
33	Research Site	Guadalajara		Mexico
34	Research Site	México		Mexico
35	Research Site	Veracruz		Mexico
36	Research Site	Den Haag		Netherlands
37	Research Site	Deurne		Netherlands
38	Research Site	Gorinchem		Netherlands
39	Research Site	Groningen		Netherlands
40	Research Site	Lichtenvoorde (gld)		Netherlands
41	Research Site	Losser		Netherlands
42	Research Site	Poortvliet		Netherlands
43	Research Site	Rotterdam		Netherlands
44	Research Site	Wildervank		Netherlands
45	Research Site	Zutphen		Netherlands
46	Research Site	Cape Town		South Africa
47	Research Site	Durban		South Africa
48	Research Site	Johannesburg		South Africa
49	Research Site	Parow		South Africa
50	Research Site	Pretoria		South Africa
51	Research Site	Umkomaas		South Africa
52	Research Site	Witbank		South Africa
53	Research Site	Alicante		Spain
54	Research Site	Alzira (Valencia)		Spain
55	Research Site	Barcelona		Spain
56	Research Site	Cornellá de Llobregat (BCN)		Spain
57	Research Site	Madrid		Spain
58	Research Site	Sevilla		Spain
59	Research Site	Göteborg		Sweden
60	Research Site	Järfälla		Sweden
61	Research Site	Lund		Sweden
62	Research Site	Malmö		Sweden
63	Research Site	Skene		Sweden
64	Research Site	Stockholm		Sweden
65	Research Site	Södertälje		Sweden
66	Research Site	Umeå		Sweden
67	Research Site	Addlestone		United Kingdom
68	Research Site	Aylesbury		United Kingdom
69	Research Site	Bath		United Kingdom
70	Research Site	Bolton		United Kingdom
71	Research Site	Bury St Edmonds		United Kingdom
72	Research Site	Cookstown		United Kingdom
73	Research Site	Coventry		United Kingdom
74	Research Site	Ecclesfield		United Kingdom
75	Research Site	Edinburgh		United Kingdom
76	Research Site	Mortimer Reading		United Kingdom
77	Research Site	Trowbridge		United Kingdom

Sponsors and Collaborators

• AstraZeneca
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Michael A. Nauck, Prof. Dr. med., Diabeteszentrum Bad Lauterberg, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR-D1690C00004.pdf

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00660907
• Other Study ID Numbers: D1690C00004
• First Posted: Apr 17, 2008
• Last Update Posted: Mar 30, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by AstraZeneca: Dapagliflozin; efficacy; safety; metformin; Type 2 diabetes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Dapagliflozin; Glipizide

Study Results

Participant Flow

Recruitment Details	The 1st patient was enrolled on 31 Mar 2008. The last patient last visit was on 15 Dec 2009. 1901 patients (pts) were screened and 1217 pts were enrolled with the aim to randomize 816. 2 randomized pts were excluded since they received no medication. Eventually, 814 pts received medication. This study was conducted at 95 centers world-wide.
Pre-assignment Detail	For participants with a metformin dose of less than 1500 mg/day, a change in metformin dose in the past 8 weeks or on an Oral Anti-Diabetic (OAD), an 8-week metformin-only dose stabilisation period occurred. A 2-week placebo lead in period occurred after the dose stabilisation period or after enrolment if dose stabilisation period was skipped.

Arm/Group Title	Dapagliflozin Plus Metformin	Glipizide Plus Metformin
Arm/Group Description	Experimental dapagliflozin plus metformin	Active Comparator glipizide plus metformin
Period Title: Overall Study
STARTED	406	408
COMPLETED	322	314
NOT COMPLETED	84	94

Baseline Characteristics

Arm/Group Title	Dapagliflozin Plus Metformin	Glipizide Plus Metformin	Total
Arm/Group Description	Experimental dapagliflozin plus metformin	Active Comparator glipizide plus metformin	Total of all reporting groups
Overall Participants	400	401	801
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (9.37)	58.6 (9.80)	58.4 (9.58)
Sex: Female, Male (Count of Participants)
Female	179 44.8%	181 45.1%	360 44.9%
Male	221 55.3%	220 54.9%	441 55.1%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	27 6.8%	34 8.5%	61 7.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	26 6.5%	24 6%	50 6.2%
White	327 81.8%	323 80.5%	650 81.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	20 5%	20 5%	40 5%
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	31.71 (5.104)	31.23 (5.053)	31.47 (5.081)
HbA1c (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	7.69 (0.855)	7.74 (0.886)	7.72 (0.870)
FPG (ng/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/mL]	162.24 (37.796)	163.91 (41.559)	163.07 (39.708)

Outcome Measures

1. Primary Outcome

Title	Adjusted Mean Change in HbA1c Levels
Description	To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on the absolute change from baseline in HbA1c level after 52 weeks double-blind treatment in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set, participants with non-missing baseline and Week 52 (LOCF) values

Arm/Group Title	Dapagliflozin Plus Metformin	Glipizide Plus Metformin
Arm/Group Description	Experimental dapagliflozin plus metformin	Active Comparator glipizide plus metformin
Measure Participants	400	401
Least Squares Mean (95% Confidence Interval) [percent]	-0.52	-0.52

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin Plus Metformin, Glipizide Plus Metformin
	Comments	The null hypothesis is given as H0: mean(treat) minus mean(reference) >= delta versus the alternative HA: mean(treat) minus mean(reference) < delta (with alpha = 0.025, one-sided)
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	non-inferior margin delta = 0.35
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significant at alpha=0.025 (1-sided). A hierarchical closed testing procedure was used to control Type I error across the primary & key secondary objectives
	Method	ANCOVA
	Comments	with treatment group as effect and baseline value as covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0569
	Estimation Comments

2. Secondary Outcome

Title	Adjusted Mean Change in Body Weight
Description	To assess the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight after 52 weeks double-blind treatment.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set, participants with non-missing baseline and Week 52 (LOCF) values

Arm/Group Title	Dapagliflozin Plus Metformin	Glipizide Plus Metformin
Arm/Group Description	Experimental dapagliflozin plus metformin	Active Comparator glipizide plus metformin
Measure Participants	400	401
Least Squares Mean (95% Confidence Interval) [kg]	-3.22	1.44

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin Plus Metformin, Glipizide Plus Metformin
	Comments	H0: mean(treat) minus mean(reference) = 0 versus the alternative HA: mean(treat) minus mean(reference) =/= 0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure
	Method	ANCOVA
	Comments	with treatment group as effect and baseline value as covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.65
	Confidence Interval	(2-Sided) 95%; -5.14 to -4.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2483
	Estimation Comments

3. Secondary Outcome

Title	Proportion of Participants With at Least One Episode of Hypoglycemia
Description	To assess the effect of dapagliflozin plus metformin treatment compared to glipizide plus metformin on the occurrence of hypoglycemic events. Least Squares Mean represents the percent of participants adjusted for HbA1c baseline value.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Dapagliflozin Plus Metformin	Glipizide Plus Metformin
Arm/Group Description	Experimental dapagliflozin plus metformin	Active Comparator glipizide plus metformin
Measure Participants	400	401
Least Squares Mean (95% Confidence Interval) [Percentage of participants]	3.5 0.9%	40.8 10.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin Plus Metformin, Glipizide Plus Metformin
	Comments	H0: proportion(treat) minus proportion(reference) = 0 versus the alternative HA: proportion(treat) minus proportion(reference) =/= 0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure
	Method	Regression, Logistic
	Comments	Based on methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, with adjustment for baseline value.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-37.2
	Confidence Interval	(2-Sided) 95%; -42.3 to -32.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.578
	Estimation Comments

4. Secondary Outcome

Title	Proportion of Participants With Body Weight Reduction of at Least 5%
Description	To evaluate the effect of dapagliflozin plus metformin compared to glipizide plus metformin on body weight assessed by a reduction after 52 weeks of at least 5% compared to baseline. Least Squares Mean represents the percent of participants adjusted for baseline value.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set, participants with non-missing baseline and Week 52 (LOCF) values

Arm/Group Title	Dapagliflozin Plus Metformin	Glipizide Plus Metformin
Arm/Group Description	Experimental dapagliflozin plus metformin	Active Comparator glipizide plus metformin
Measure Participants	400	401
Least Squares Mean (95% Confidence Interval) [Percentage of participants]	33.3 8.3%	2.5 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin Plus Metformin, Glipizide Plus Metformin
	Comments	H0: proportion(treat) minus proportion(reference) = 0 versus the alternative HA: proportion(treat) minus proportion(reference) =/= 0
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significant at alpha=0.05 (2-sided). Key secondary endpoints are tested following a hierarchical closed testing procedure
	Method	Regression, Logistic
	Comments	Based on methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, with adjustment for baseline value.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	30.8
	Confidence Interval	(2-Sided) 95%; 26.0 to 35.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.480
	Estimation Comments

Adverse Events

Time Frame	Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week double-blind treatment plus 4/30 days or up to follow-up visit if earlier, or up to and including the start date of extension period if earlier.
Adverse Event Reporting Description	Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
Arm/Group Title	Dapagliflozin Plus Metformin		Glipizide Plus Metformin
Arm/Group Description	Experimental dapagliflozin plus metformin		Active Comparator glipizide plus metformin
All Cause Mortality
	Dapagliflozin Plus Metformin		Glipizide Plus Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dapagliflozin Plus Metformin		Glipizide Plus Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/406 (8.6%)		46/408 (11.3%)
Blood and lymphatic system disorders
Anaemia	0/406 (0%)		2/408 (0.5%)
Cardiac disorders
Myocardial Infarction	1/406 (0.2%)		3/408 (0.7%)
Acute Coronary Syndrome	1/406 (0.2%)		0/408 (0%)
Acute Myocardial Infarction	0/406 (0%)		1/408 (0.2%)
Angina Pectoris	1/406 (0.2%)		1/408 (0.2%)
Atrial Fibrillation	1/406 (0.2%)		0/408 (0%)
Atrioventricular Block Complete	0/406 (0%)		1/408 (0.2%)
Bradycardia	0/406 (0%)		1/408 (0.2%)
Cardiac Arrest	1/406 (0.2%)		0/408 (0%)
Cardiac Failure	0/406 (0%)		1/408 (0.2%)
Cardiac Failure Congestive	0/406 (0%)		1/408 (0.2%)
Coronary Artery Disease	1/406 (0.2%)		1/408 (0.2%)
Left Ventricular Failure	1/406 (0.2%)		0/408 (0%)
Ventricular Arrhythmia	1/406 (0.2%)		0/408 (0%)
Eye disorders
Cataract	0/406 (0%)		1/408 (0.2%)
Retinal Detachment	1/406 (0.2%)		1/408 (0.2%)
Gastrointestinal disorders
Abdominal Pain	0/406 (0%)		1/408 (0.2%)
Abdominal Pain Upper	1/406 (0.2%)		0/408 (0%)
Anal Fissure	0/406 (0%)		1/408 (0.2%)
Constipation	1/406 (0.2%)		0/408 (0%)
Dyspepsia	0/406 (0%)		1/408 (0.2%)
Gastritis	1/406 (0.2%)		0/408 (0%)
Haemorrhoids	1/406 (0.2%)		0/408 (0%)
Upper Gastrointestinal Haemorrhage	1/406 (0.2%)		0/408 (0%)
General disorders
Chest Pain	0/406 (0%)		1/408 (0.2%)
Non-Cardiac Chest Pain	0/406 (0%)		1/408 (0.2%)
Sudden Death	0/406 (0%)		1/408 (0.2%)
Hepatobiliary disorders
Cholecystitis	0/406 (0%)		1/408 (0.2%)
Cholecystitis Acute	0/406 (0%)		1/408 (0.2%)
Cholelithiasis	1/406 (0.2%)		0/408 (0%)
Hepatic Cirrhosis	1/406 (0.2%)		0/408 (0%)
Infections and infestations
Diverticulitis	0/406 (0%)		2/408 (0.5%)
Bronchitis	1/406 (0.2%)		1/408 (0.2%)
Erysipelas	0/406 (0%)		1/408 (0.2%)
Gastroenteritis	0/406 (0%)		1/408 (0.2%)
Gastroenteritis Viral	1/406 (0.2%)		0/408 (0%)
Liver Abscess	1/406 (0.2%)		0/408 (0%)
Lower Respiratory Tract Infection	1/406 (0.2%)		0/408 (0%)
Pneumonia	1/406 (0.2%)		1/408 (0.2%)
Pyelonephritis	0/406 (0%)		1/408 (0.2%)
Sepsis	1/406 (0.2%)		0/408 (0%)
Septic Shock	1/406 (0.2%)		0/408 (0%)
Injury, poisoning and procedural complications
Overdose	0/406 (0%)		2/408 (0.5%)
Ankle Fracture	1/406 (0.2%)		1/408 (0.2%)
Clavicle Fracture	0/406 (0%)		1/408 (0.2%)
Contusion	0/406 (0%)		1/408 (0.2%)
Humerus Fracture	0/406 (0%)		1/408 (0.2%)
Multiple Injuries	1/406 (0.2%)		0/408 (0%)
Postoperative Renal Failure	0/406 (0%)		1/408 (0.2%)
Road Traffic Accident	0/406 (0%)		1/408 (0.2%)
Wrist Fracture	0/406 (0%)		1/408 (0.2%)
Investigations
Creatinine Renal Clearance Decreased	1/406 (0.2%)		0/408 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	0/406 (0%)		3/408 (0.7%)
Hyponatraemia	1/406 (0.2%)		0/408 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/406 (0%)		1/408 (0.2%)
Intervertebral Disc Protrusion	0/406 (0%)		1/408 (0.2%)
Rotator Cuff Syndrome	0/406 (0%)		1/408 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	3/406 (0.7%)		1/408 (0.2%)
Basal Cell Carcinoma	0/406 (0%)		1/408 (0.2%)
Breast Cancer	1/406 (0.2%)		0/408 (0%)
Bronchial Carcinoma	0/406 (0%)		1/408 (0.2%)
Nervous system disorders
Carotid Artery Stenosis	1/406 (0.2%)		0/408 (0%)
Cerebral Thrombosis	1/406 (0.2%)		0/408 (0%)
Cervicobrachial Syndrome	1/406 (0.2%)		0/408 (0%)
Loss Of Consciousness	1/406 (0.2%)		0/408 (0%)
Migraine	0/406 (0%)		1/408 (0.2%)
Transient Ischaemic Attack	1/406 (0.2%)		0/408 (0%)
Psychiatric disorders
Depression Suicidal	0/406 (0%)		1/408 (0.2%)
Obsessive-Compulsive Disorder	0/406 (0%)		1/408 (0.2%)
Renal and urinary disorders
Diabetic Nephropathy	1/406 (0.2%)		0/408 (0%)
Nephrolithiasis	0/406 (0%)		1/408 (0.2%)
Urinary Incontinence	0/406 (0%)		1/408 (0.2%)
Reproductive system and breast disorders
Uterine Prolapse	2/406 (0.5%)		0/408 (0%)
Respiratory, thoracic and mediastinal disorders
Alveolitis Allergic	1/406 (0.2%)		0/408 (0%)
Asthma	0/406 (0%)		1/408 (0.2%)
Pulmonary Embolism	1/406 (0.2%)		0/408 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/406 (0.2%)		0/408 (0%)
Urticaria	1/406 (0.2%)		0/408 (0%)
Other (Not Including Serious) Adverse Events
	Dapagliflozin Plus Metformin		Glipizide Plus Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	163/406 (40.1%)		260/408 (63.7%)
Endocrine disorders
Hypoglycemia	14/406 (3.4%)		162/408 (39.7%)
Gastrointestinal disorders
Diarrhoea	19/406 (4.7%)		26/408 (6.4%)
Infections and infestations
Nasopharyngitis	43/406 (10.6%)		61/408 (15%)
Upper Respiratory Tract Infection	24/406 (5.9%)		31/408 (7.6%)
Influenza	30/406 (7.4%)		30/408 (7.4%)
Urinary Tract Infection	30/406 (7.4%)		17/408 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	11/406 (2.7%)		21/408 (5.1%)
Nervous system disorders
Dizziness	15/406 (3.7%)		37/408 (9.1%)
Tremor	1/406 (0.2%)		31/408 (7.6%)
Headache	21/406 (5.2%)		17/408 (4.2%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	5/406 (1.2%)		27/408 (6.6%)
Vascular disorders
Hypertension	30/406 (7.4%)		35/408 (8.6%)

Limitations/Caveats

For participants who did not complete 52 weeks LOCF (last observation carried forward) was used.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an Investigator requests permission to publish data from this study any such publication is to be agreed with AstraZeneca (AZ) in advance. The investigator agrees to provide AZ as soon as possible with drafts of proposed publications. Unless otherwise agreed, AZ shall have a period of 60 days from receipt of the proposed final manuscript to review it and may within such time require that submission for publication of the manuscript be delayed in order for AZ to file patent applications.