A Phase III Study of BMS-512148 (Dapagliflozin) in Patien... | NCT00528372

Status Module

Name	Class
Bristol-Myers Squibb	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1: Dapagliflozin, 2.5 mg AM	Experimental	Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks.	Drug: Dapagliflozin Drug: Metformin
Group 1: Dapagliflozin, 10 mg AM	Experimental	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks.	Drug: Dapagliflozin Drug: Metformin
Group 1: Dapagliflozin 2.5 mg PM	Experimental	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks.	Drug: Dapagliflozin Drug: Metformin
Group 1: Dapagliflozin, 5 mg PM	Experimental	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks.	Drug: Dapagliflozin Drug: Metformin
Group 1: Dapagliflozin, 10 mg PM	Experimental	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dapagliflozin	Drug	Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks	Group 1: Dapagliflozin 2.5 mg PM Group 1: Dapagliflozin, 10 mg AM

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1	HbA1c was measured by a central laboratory. Data after rescue medication was excluded from this analysis. 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Evening dosing groups were summarized as exploratory endpoints.	Baseline to Week 24 (end of Short-term Period)
Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2	HbA1c was measured by a central laboratory. Data after rescue medication was excluded from this analysis. 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.	Baseline to Week 24 (end of Short-term Period)

Secondary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1	Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized in secondary efficacy analyses. Data after rescue medication were excluded from this analysis. 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. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria

Males and females, aged 18 to 77 years
Type 2 diabetes with inadequate glycemic control, defined as: Group 1, hemoglobin A1c (HbA1c) ≥7% and ≤10%; Group 2, HbA1c ≥10.1% and ≤12.0%
Drug naive, defined as never having received prescription medications for diabetes, having received prescription medications for diabetes for <24 weeks since the original diagnosis
C-peptide ≥1.0 ng/mL at enrollment
Body Mass Index ≤ 45.0 kg/m^2 at enrollment

Key Exclusion Criteria

Urine albumin:creatinine ratio >1,800 mg/g
Aspartate aminotransferase >3*upper limit of normal (ULN)
Alanine aminotransferase >3*ULN
Serum total bilirubin >2*ULN
Serum creatinine ≥1.5 mg/dL for men; ≥1.4 mg/dLfor women
Calcium value outside of the central laboratory normal reference range
Positive hepatitis B surface antigen
Positive anti-hepatitis C virus antibody
Hemoglobin ≤11 g/dL for men; hemoglobin ≤10 g/dL for women
Creatine kinase >3*ULN
Abnormal free T4 values
History of diabetes insipidus
Symptoms of poorly controlled diabetes, including marked polyuria and polydipsia with greater than 10% weight loss in the 3 months prior to enrollment
History of diabetic ketoacidosis or hyperosmolar nonketotic coma
Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg
Any of the following within 6 months of enrollment: Myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable congestive heart failure (CHF), CHF New York Heart Association Class III or IV status, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia
History of unstable or rapidly progressing renal disease
Conditions of congenital renal glucosuria
Significant hepatic disease, including chronic active hepatitis and/or severe hepatic insufficiency
Documented history of hepatotoxicity with any medication
Documented history of severe hepatobiliary disease
History of hemoglobinopathy, with the exception of sickle cell trait, thalassemia minor, or chronic or recurrent hemolysis
Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of >400 mL of blood during the 6 weeks prior to enrollment
Malignancy (with the exception of treated basal cell or treated squamous cell carcinoma) within 5 years of enrollment visit
Known immunocompromised status, including individuals who had undergone organ transplantation or who had positive HIV results
Administration of any antidiabetic therapy for more than 14 days (consecutive or not) during the 12 weeks prior to enrollment
Administration of any antidiabetic therapy, other than any previously specified, at any dose, at any time during the 4 weeks prior to enrollment
Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months prior to enrollment
History of bariatric surgery or lap-band procedure
Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days of enrollment

Name	Affiliation	Role
Anna Maria Langkilde	AstraZeneca	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
43rd Medical Associates, P.C.		Phoenix	Arizona	85051	United States
Clin Res Advantage, Inc/East Valley Family Physicians, Plc

PubMed Identifier	Type	Citation	Retractions
20566676	Result	Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010 Oct;33(10):2217-24. doi: 10.2337/dc10-0612. Epub 2010 Jun 21.
25381876	Result

Label	URL
MB102013\_Clinical\_Study\_Protocol	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group 1: Dapagliflozin Placebo	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG002	Group 1: Dapagliflozin, 5 mg AM	Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG003	Group 1: Dapagliflozin, 10 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG004	Group 1: Dapagliflozin, 2.5 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG005	Group 1: Dapagliflozin, 5 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG006	Group 1: Dapagliflozin, 10 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG007	Group 2: Dapagliflozin, 5 mg AM	Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG008	Group 2: Dapagliflozin, 10 mg AM	Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
BG009	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1

HbA1c was measured by a central laboratory. Data after rescue medication was excluded from this analysis. 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Evening dosing groups were summarized as exploratory endpoints.

Randomized participants with nonmissing baseline and Week 24 LOCF values

Posted

Mean

Standard Error

Percent

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG002	Group 1: Dapagliflozin, 5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG003	Group 1: Dapagliflozin, 10 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG004	Group 1: Dapagliflozin, 2.5 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.
OG005	Group 1: Dapagliflozin, 5 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.
OG006	Group 1: Dapagliflozin, 10 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.

Units	Counts
Participants	OG00072 OG00164 OG00261 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.23± 0.1044 OG001-0.58± 0.1107 OG002-0.77± 0.1134 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.0207	Tested at alpha=0.019, applying the Dunnett adjustment	Mean Difference (Final Values)	-0.35	Standard Error of the Mean	0.1522								No	Superiority or Other
OG000 OG002		ANCOVA

Secondary

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized in secondary efficacy analyses. Data after rescue medication were excluded from this analysis. 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. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.

Randomized participants with nonmissing baseline and Week 24 LOCF values

Posted

Mean

Standard Error

mg/dL

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001

Secondary

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2

Group 2 was an exploratory group, included to obtain initial efficacy and safety data. No comparator arm was included. Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Data after rescue medication were excluded from this analysis. 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. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.

Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment and nonmissing baseline and Week 24 LOCF values

Posted

Mean

Standard Deviation

mg/dL

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 2: Dapagliflozin, 5 mg AM	Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.

Secondary

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined). Data after rescue medication was excluded from this analysis. 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.

Randomized participants with nonmissing baseline and Week 24 values

Posted

Mean

Standard Error

Kilograms

From Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM

Secondary

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined). Data after rescue medication was excluded from this analysis. 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.Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.

Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment nonmissing baseline and Week 24 LOCF values.

Posted

Mean

Standard Deviation

Kilograms

From Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 2: Dapagliflozin, 5 mg AM	Participants with hemoglobin A1c (HbA1c) ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.

Secondary

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. 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.

Randomized participants with nonmissing baseline and Week 24 LOCF values

Posted

Mean

Standard Error

mg/dL

Baseline to Week 1 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.

Secondary

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. 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.

Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment with nonmissing baseline and Week 24 LOCF values

Posted

Mean

Standard Deviation

mg/dL

Baseline to Week 1

ID	Title	Description
OG000	Group 2: Dapagliflozin, 5 mg AM	Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.
OG001	Group 2: Dapagliflozin, 10 mg AM

Secondary

Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Randomized participants who had nonmissing baseline and Week 24 LOCF values

Posted

Number

Percentage of participants

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.

Secondary

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. HbA1c was measured as % of hemoglobin by a central laboratory. The population included randomized patients who received treatment and had baseline HbA1c >9.0%. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of double-blind study drug. In cases where time of the first dose or 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 drug. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered exploratory, included to obtain initial data. No comparator arm was included. Thus, only key safety and efficacy analyses were performed in Group 2.

Randomized participants with nonmissing baseline and Week24 LOCF values.

Posted

Mean

Standard Error

Percent

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.

Secondary

Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. 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. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Randomized participants with baseline BMI ≥27 kg/m^2 and nonmissing baseline and Week 24 LOCF values

Posted

Mean

Standard Error

Percent

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001

Secondary

Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Randomized participants with HbA1c values at both baseline and Week 24 (LOCF)

Posted

Number

Percentage of participants

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.

Secondary

Adjusted Mean Change From Baseline to Week 24 in Total Body Weight in Patients With Baseline Body Mass Index ≥27 kg/m^2 (Last Observation Carried Forward)

Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available) was determined. Data after rescue medication was excluded from this analysis. 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. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Randomized participants with baseline BMI ≥27 kg/m^2 and nonmissing baseline and Week 24 values

Posted

Mean

Standard Error

Kilograms

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.

Secondary

Number of Participants With Adverse Events (AE), Hypoglycemia, Related AEs, Death as Outcome, Related Serious AEs (SAEs), SAEs and AEs Leading to Discontinuation, and Hypoglycemia Leading to Discontinuation (Short-term + Long-term Periods)

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug. Includes non-SAEs and hypoglycemia with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 4 days. Includes SAEs with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 30 days.

Randomized participants who received at least 1 dose of study medication

Posted

Number

Participants

Day 1 to Week 102 (end of Long-term Period) + 30 days

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo, AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. In addition, during the long-term treatment period, participants received metformin, 500 mg, with the morning meal.
OG001

Primary

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2

HbA1c was measured by a central laboratory. Data after rescue medication was excluded from this analysis. 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.

Randomized participants with HbA1c ≥10.1% and ≤12% at enrollment and nonmissing baseline and Week 24 LOCF values

Posted

Mean

Standard Deviation

Percent

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 2: Dapagliflozin, 5 mg AM	Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria. During the long-term treatment period, participants received metformin, 500 mg, with the morning meal.

Secondary

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods)

Baseline was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from baseline up to and including the last day of treatment plus 4 days. Data after rescue were also included. ULN=upper limit of normal; preRX=pretreatment. Phosphorus, inorganic (high) defined as >=5.6 mg/dL for ages 17-65 years or >=5.1 mg/dL for ages >=66.

Randomized participants who received at least 1 dose of study medication and with laboratory test results available

Posted

Number

Participants

Baseline to Week 102 (end of Long-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, AM, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.

Secondary

Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods)

Data after rescue was included. AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Randomized participants who received at least 1 dose of study medication and with laboratory test results available

Posted

Number

Participants

Day 1 to Week 102 (end of Long-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG002

Secondary

Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF])

12-Lead ECGs were performed at entry into lead-in period Day -7 visit and Week 24/end of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter, and data after rescue were included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Randomized participants who received at least 1 dose of study medication and who had measurements available

Posted

Number

Participants

Baseline to Week 24 (end of Short-term Period)

ID	Title	Description
OG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.
OG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1: Dapagliflozin Placebo AM & PM	Participants with hemoglobin AIc (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.	5	75	40	75
EG001	Group 1: Dapagliflozin, 2.5 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.	6	65	40	65
EG002	Group 1: Dapagliflozin, 5 mg AM	Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.	4	64	33	64
EG003	Group 1: Dapagliflozin, 10 mg AM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.	1	70	41	70
EG004	Group 1: Dapagliflozin, 2.5 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.	7	67	38	67
EG005	Group 1: Dapagliflozin, 5 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.	5	68	39	68
EG006	Group 1: Dapagliflozin, 10 mg PM	Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks. Participants also received metformin tablets, 500-2000 mg, orally as needed for rescue based on protocol specific criteria.	3	76	39	76

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG0030 affected70 at risk EG0041 affected67 at risk EG0050 affected68 at risk EG0060 affected76 at risk
Femoral artery occlusion	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Pneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Albumin urine present	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Influenza	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Venous thrombosis	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0021 affected64 at risk EG003
Glomerulonephritis acute	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0021 affected64 at risk EG003
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Malacoplakia vesicae	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Adverse drug reaction	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Diabetic hyperosmolar coma	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Pilonidal cyst	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0021 affected64 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0021 affected64 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Urine albumin/creatinine ratio increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Chest pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0021 affected64 at risk EG003
Colon neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Mitral valve incompetence	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Staphylococcal bacteraemia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0005 affected75 at risk EG0012 affected65 at risk EG0021 affected64 at risk EG0034 affected70 at risk EG0045 affected67 at risk EG0054 affected68 at risk EG0064 affected76 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0012 affected65 at risk EG0021 affected64 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0005 affected75 at risk EG0016 affected65 at risk EG0022 affected64 at risk EG003
Influenza	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 affected75 at risk EG0017 affected65 at risk EG0025 affected64 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0006 affected75 at risk EG0011 affected65 at risk EG0026 affected64 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0004 affected75 at risk EG0014 affected65 at risk EG0021 affected64 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected75 at risk EG0010 affected65 at risk EG0020 affected64 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0005 affected75 at risk EG0013 affected65 at risk EG0024 affected64 at risk EG003
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected75 at risk EG0013 affected65 at risk EG0021 affected64 at risk EG003
Hypertension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected75 at risk EG0014 affected65 at risk EG0024 affected64 at risk EG003
Oedema peripheral	General disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected75 at risk EG0011 affected65 at risk EG0022 affected64 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected75 at risk EG0014 affected65 at risk EG0023 affected64 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected75 at risk EG0016 affected65 at risk EG0025 affected64 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected75 at risk EG0012 affected65 at risk EG0022 affected64 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected75 at risk EG0013 affected65 at risk EG0023 affected64 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 affected75 at risk EG0013 affected65 at risk EG0025 affected64 at risk EG003
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected75 at risk EG0014 affected65 at risk EG0020 affected64 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 affected75 at risk EG0012 affected65 at risk EG0021 affected64 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected75 at risk EG0014 affected65 at risk EG0023 affected64 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected75 at risk EG0011 affected65 at risk EG0020 affected64 at risk EG003
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0009 affected75 at risk EG0016 affected65 at risk EG0025 affected64 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0007 affected75 at risk EG00111 affected65 at risk EG0025 affected64 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D006302	Health Services Research
D006285	Health Planning
D004472	Health Care Economics and Organizations
D003695	Delivery of Health Care
D017530	Health Care Quality, Access, and Evaluation

ID	Term
C529054	dapagliflozin
D008687	Metformin
D006301	Health Services Needs and Demand