Efficacy and Safety of Dapagliflozin, Added to Therapy of... | NCT00673231

Name	Class
Bristol-Myers Squibb	INDUSTRY

Efficacy and Safety of Dapagliflozin, Added to Therapy of... | NCT00673231 | Trialant

Arms/Interventions Module

Label	Type	Description	Intervention Names
1	Experimental	2.5mg	Drug: Dapagliflozin
2	Experimental	5mg	Drug: Dapagliflozin
3	Experimental	10mg	Drug: Dapagliflozin
4	Placebo Comparator		Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dapagliflozin	Drug	tablet oral 2.5 mg total daily dose once daily 48 weeks (= 24 week randomised treatment period + 24 week study extension period I)	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change in HbA1c Levels	To assess the efficacy of 2.5 mg, 5 mg and 10 mg dapagliflozin compared to placebo as add-on therapy to insulin in improving glycaemic control in participants with type 2 diabetes who have inadequate glycaemic control on ≥ 30 IU injectable insulin daily for at least 8 weeks prior to enrolment, as determined by the change in HbA1c levels from baseline to Week 24, excluding data after insulin up-titration.	Baseline to Week 24

Secondary Outcomes

Measure	Description	Time Frame
Adjusted Mean Change in Body Weight	To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing body weight or causing less weight gain as compared to placebo added to insulin treatment after 24 weeks of treatment (LOCF), excluding data after insulin up-titration.	Baseline to Week 24

Other Outcomes

Measure	Description	Time Frame
Proportion of Participants With Lack of Glycemic Control	Participants with lack of glycemic control or insulin up-titration for failing to achieve pre-specified glycemic targets	Baseline to Week 24

Contacts/Locations Module

Name	Affiliation	Role
John Wilding, MD	Clinical Sciences CentreUniversity Hospital AintreeLongmoor LaneLiverpool, UK	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Fresno	California		United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38770818	Derived	Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.
33372185

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Placebo
FG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Withdrawal by Subject		FG00014 subjects FG00110 subjects FG0028 subjects FG0036 subjects
Adverse Event		FG0006 subjects FG0015 subjects FG0029 subjects FG0036 subjects
Lost to Follow-up		FG0001 subjects FG0012 subjects FG0021 subjects FG0032 subjects
Death		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects
Study criteria,compliance,safety, other		FG0008 subjects FG0015 subjects FG0027 subjects FG0034 subjects

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo
BG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks
BG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks
BG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00058.8± 8.61 BG00159.8± 7.64 BG00259.3± 7.91 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00098 BG001102 BG002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG000186 BG001190 BG002

Body Mass Index

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00033.14± 5.862 BG00132.95± 5.032 BG002

HbA1C

Mean

Standard Deviation

Percent

Title

Denominators

Categories

Title	Measurements
	BG0008.47± 0.768 BG0018.46± 0.780 BG002

Fasting plasma glucose

Mean

Standard Deviation

mg/dl

Title

Denominators

Categories

Title	Measurements
	BG000170.62± 57.165 BG001180.11± 59.9 BG002

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 in HbA1c Levels

To assess the efficacy of 2.5 mg, 5 mg and 10 mg dapagliflozin compared to placebo as add-on therapy to insulin in improving glycaemic control in participants with type 2 diabetes who have inadequate glycaemic control on ≥ 30 IU injectable insulin daily for at least 8 weeks prior to enrolment, as determined by the change in HbA1c levels from baseline to Week 24, excluding data after insulin up-titration.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

Percent

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Placebo
OG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks
OG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks
OG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks

Units	Counts
Participants	OG000188 OG001198 OG002210 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.30(-0.40 to -0.20) OG001-0.75(-0.85 to -0.65) OG002-0.82(-0.92 to -0.73) 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	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0 (with alpha = 0.019 applying Dunnett's adjustment, two-sided)	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.019 (2-sided) applying Dunnett's adjustment. A hierarchical closed testing procedure was used to control the Type I error rate across the primary and key secondary endpoints.	Mean Difference (Final Values)	-0.45	Standard Error of the Mean	0.0726	2-Sided	95	-0.59	-0.31				No

Secondary

Adjusted Mean Change in Body Weight

To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing body weight or causing less weight gain as compared to placebo added to insulin treatment after 24 weeks of treatment (LOCF), excluding data after insulin up-titration.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Placebo
OG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks
OG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks
OG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks

Secondary

Adjusted Mean Change in Calculated Mean Daily Insulin Dose

To examine whether treatment with dapagliflozin in combination with insulin leads to a lower absolute calculated mean daily insulin dose as compared to placebo added to insulin treatment alone, from baseline to week 24, including data after insulin up-titration.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

IU/day

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Placebo
OG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks
OG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks
OG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks

Secondary

Proportion of Participants With Calculated Mean Daily Insulin Dose Reduction

To examine whether treatment with dapagliflozin in combination with insulin leads to higher percentage of participants with calculated mean daily insulin dose reduction from baseline to week 24 (i.e. reduction >= 10%) as compared to placebo added to insulin treatment.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

Percentage of participants

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Placebo
OG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks
OG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks
OG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks

Secondary

Adjusted Mean Change in Fasting Plasma Glucose (FPG)

To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing Fasting Plasma Glucose (FPG) as compared to placebo added to insulin treatment after 24 weeks of treatment, excluding data after insulin up-titration.

Full Analysis Set, participants with non-missing baseline and Week 24 (LOCF) values

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Placebo
OG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks
OG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks
OG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks

Other Pre-specified

Proportion of Participants With Lack of Glycemic Control

Participants with lack of glycemic control or insulin up-titration for failing to achieve pre-specified glycemic targets

Full Analysis Set

Posted

Number

Participants

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Placebo
OG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks
OG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks
OG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks

Units	Counts

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo	14	197	115	197
EG001	Dapagliflozin 2.5mg	Dapagliflozin tablet oral 2.5 mg total daily dose once daily 24 weeks	15	202	135	202
EG002	Dapagliflozin 5mg	Dapagliflozin tablet oral 5 mg total daily dose once daily 24 weeks	10	212	128	212
EG003	Dapagliflozin 10mg	Dapagliflozin tablet oral 10 mg total daily dose once daily 24 weeks	14	196	107	196

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina Pectoris	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0021 affected212 at risk EG0030 affected196 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Cardiogenic Shock	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Sick Sinus Syndrome	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Vertigo Positional	Ear and labyrinth disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Glaucoma	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Change Of Bowel Habit	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Small Intestinal Obstruction	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Non-Cardiac Chest Pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Abscess Limb	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Ear Infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Erysipelas	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Laryngitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Ankle Fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Dislocation Of Joint Prosthesis	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Hip Fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Thrombosis In Device	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Tibia Fracture	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0022 affected212 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Rotator Cuff Syndrome	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Tenosynovitis	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Bile Duct Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Breast Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Chronic Lymphocytic Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Hepatic Neoplasm Malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Pancreatic Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Pancreatic Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Prostate Cancer Recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Transient Ischaemic Attack	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0002 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Burning Sensation	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Carotid Artery Occlusion	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Cerebrovascular Accident	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Hypoglycaemic Coma	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Neuropathy Peripheral	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0011 affected202 at risk EG0020 affected212 at risk EG003
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Aortic Valve Replacement	Surgical and medical procedures	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Diabetic Microangiopathy	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0021 affected212 at risk EG003
Hypertension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003
Thrombophlebitis Superficial	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected197 at risk EG0010 affected202 at risk EG0020 affected212 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00022 affected197 at risk EG00128 affected202 at risk EG00229 affected212 at risk EG00317 affected196 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0006 affected197 at risk EG00110 affected202 at risk EG00212 affected212 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG00010 affected197 at risk EG0015 affected202 at risk EG0026 affected212 at risk EG003
Headache	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00014 affected197 at risk EG0018 affected202 at risk EG0029 affected212 at risk EG003
Hypertension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG00016 affected197 at risk EG00111 affected202 at risk EG00213 affected212 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG00010 affected197 at risk EG0018 affected202 at risk EG0024 affected212 at risk EG003
Hypoglycemia	Endocrine disorders	MedDRA 12.0	Systematic Assessment	EG00083 affected197 at risk EG001111 affected202 at risk EG002101 affected212 at risk EG003

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	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	0.0001	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-1.00	Standard Error of the Mean	0.2560	2-Sided	95	-1.50	-0.49	No	Superiority or Other
OG000 OG002	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA		<0.0001	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-1.00	Standard Error of the Mean	0.2523	2-Sided	95	-1.50	-0.50	No	Superiority or Other
OG000 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-1.68	Standard Error of the Mean	0.2578	2-Sided	95	-2.19	-1.18	No	Superiority or Other

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	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-6.87	Standard Error of the Mean	1.3195	2-Sided	95	-9.46	-4.28	No	Superiority or Other
OG000 OG002	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-5.69	Standard Error of the Mean	1.3045	2-Sided	95	-8.25	-3.13	No	Superiority or Other
OG000 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-6.23	Standard Error of the Mean	1.3286	2-Sided	95	-8.84	-3.63	No	Superiority or Other

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	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0	Regression, Logistic	Methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, adjustment for stratum (other oral anti-diab med use) and baseline value.	0.0427	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Risk Difference (RD)	7.2	Standard Error of the Mean	3.536	2-Sided	95	0.2	14.1	No	Superiority or Other
OG000 OG002	H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0	Regression, Logistic	Methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, adjustment for stratum (other oral anti-diab med use) and baseline value.	0.0903	not significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Risk Difference (RD)	5.8	Standard Error of the Mean	3.434	2-Sided	95	-0.9	12.5	No	Superiority or Other
OG000 OG003	H0: proportion(treat) minus proportion(placebo) = 0 versus the alternative HA: proportion(treat) minus proportion(placebo) =/= 0	Regression, Logistic	Methodology of Zhang, Tsiatis & Davidian and Davidian, Tsiatis, Zhang & Lu, adjustment for stratum (other oral anti-diab med use) and baseline value.	0.0166	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Risk Difference (RD)	8.7	Standard Error of the Mean	3.634	2-Sided	95	1.6	15.8	No	Superiority or Other

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	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	0.0008	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-15.8	Standard Error of the Mean	4.684	2-Sided	95	-25.0	-6.6	No	Superiority or Other
OG000 OG002	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.		Not significant. Hierarchical closed testing procedure within treatment group stopped at previous endpoint.	Mean Difference (Final Values)	-22.1	Standard Error of the Mean	4.616	2-Sided	95	-31.2	-13.1	No	Superiority or Other
OG000 OG003	The null hypothesis is given as H0: mean(treat) minus mean(placebo) = 0 versus HA: mean(treat) minus mean(placebo) =/= 0	ANCOVA	with treatment group (all treatment groups included) and stratum (other oral anti-diabetic med use) as effect and baseline value as covariate.	<0.0001	significant at alpha=0.05 (2-sided). Primary and key secondary endpoints are tested following a hierarchical closed testing procedure within treatment group.	Mean Difference (Final Values)	-25.0	Standard Error of the Mean	4.718	2-Sided	95	-34.3	-15.8	No	Superiority or Other

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