Safety and Efficacy of BI 10773 as add-on to Insulin Regi... | NCT01306214

ID	Type	Description	Link
2010-019968-37	EudraCT Number	EudraCT

Name	Class
Eli Lilly and Company	INDUSTRY

Safety and Efficacy of BI 10773 as add-on to Insulin Regi... | NCT01306214 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BI 10773 low dose	Experimental	BI 10773 low dose once daily	Drug: Placebo Drug: BI 10773
BI 10773 high dose	Experimental	BI 10733 high dose once daily	Drug: Placebo Drug: BI 10773
Placebo	Placebo Comparator	Placebo tablets matching BI 10773	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo matching BI 10773 low dose	Placebo
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c After 18 Weeks of Treatment	The primary endpoint was the change from baseline in HbA1c after 18 weeks of treatment.	Baseline and 18 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Insulin Dose After 52 Weeks of Treatment	The secondary endpoint is change from baseline in insulin dose after 52 weeks of treatment	Baseline and 52 weeks
Change From Baseline in Body Weight After 52 Weeks of Treatment

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1245.49.10005 Boehringer Ingelheim Investigational Site		Birmingham	Alabama		United States
1245.49.10011 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35472672	Derived	Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.
24929430

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
FG001	Empagliflozin 10 mg	Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Death		FG0000 subjects FG0010 subjects FG0021 subjects
Lost to Follow-up		FG0003 subjects FG0015 subjects FG0024 subjects
Withdrawal by Subject		FG00024 subjects FG00122 subjects FG00216 subjects
Not treated		FG0001 subjects FG0011 subjects FG0021 subjects

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
BG001	Empagliflozin 10 mg	Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
BG002	Empagliflozin 25 mg	Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily
BG003	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
	OG000-0.50± 0.05 OG001-0.94± 0.05 OG002-1.02± 0.05

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	For the primary endpoint, the testing of the superiority hypothesis versus placebo was: Hypothesis test: H0: No difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 10 mg and placebo Ha: A difference in change from baseline to Week 18 in HbA1c (%) between Empagliflozin 10 mg and placebo	ANCOVA	ANCOVA Model includes baseline HbA1c as a covariate and baseline eGFR, geographic region, baseline background medication, treatment as fixed effects.	<0.0001	Hierarchical testing to adjust for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 18 was the first step in each hierarchical sequence.	Adjusted mean difference	-0.44	Standard Error of the Mean	0.08	2-Sided	97.5	-0.61	-0.27

Secondary

Change From Baseline in Insulin Dose After 52 Weeks of Treatment

The secondary endpoint is change from baseline in insulin dose after 52 weeks of treatment

Per Protocol Set-patients in FAS without important protocol violations leading to exclusion, completed minimum treatment of 357 days and did not prematurely discontinue. Values after start of antidiabetic rescue therapy (week 52 definition) were set to missing and last observation carried forward (LOCF-52) was used for imputation of missing values.

Posted

Least Squares Mean

Standard Error

IU/day

Baseline and 52 weeks

ID	Title	Description
OG000	Placebo	Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
OG001	Empagliflozin 10 mg	Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
OG002	Empagliflozin 25 mg	Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily

Secondary

Change From Baseline in Body Weight After 52 Weeks of Treatment

The secondary endpoint was the change from baseline in body weight after 52 weeks of treatment

Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)

Posted

Least Squares Mean

Standard Error

Baseline and 52 weeks

ID	Title	Description
OG000	Placebo	Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
OG001	Empagliflozin 10 mg	Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
OG002	Empagliflozin 25 mg	Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily

Units	Counts
Participants

Secondary

Change From Baseline in HbA1c After 52 Weeks of Treatment

The secondary endpoint was the change from baseline in HbA1c after 52 weeks of treatment

Per Protocol Set (PPS) - completers at week 52 - using LOCF at week 52 (LOCF-52)

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline and 52 weeks

ID	Title	Description
OG000	Placebo	Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily
OG001	Empagliflozin 10 mg	Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily
OG002	Empagliflozin 25 mg	Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo matching empagliflozin 10 mg tablet plus placebo matching empagliflozin 25 mg tablet once daily	22	188	146	188
EG001	Empagliflozin 10 mg	Empagliflozin film-coated 10 mg tablet plus one placebo matching empagliflozin 25 mg tablet once daily	20	186	135	186
EG002	Empagliflozin 25 mg	Empagliflozin film-coated 25 mg tablet plus one placebo matching empagliflozin 10 mg tablet once daily	22	189	140	189

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0013 affected186 at risk EG0021 affected189 at risk
Anal abscess	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Appendicitis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Diabetic gangrene	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Gastrointestinal infection	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Lobar pneumonia	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Sepsis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Subcutaneous abscess	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Urinary tract infection	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Ependymoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Pancreatic carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Anaemia	Blood and lymphatic system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Sarcoidosis	Immune system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Depression	Psychiatric disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Carpal tunnel syndrome	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Cerebrovascular accident	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Cervicobrachial syndrome	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Convulsion	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Grand mal convulsion	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Migraine	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Radiculitis	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Syncope	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0021 affected189 at risk
Amaurosis	Eye disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Angle closure glaucoma	Eye disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Pterygium	Eye disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Vertigo	Ear and labyrinth disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0012 affected186 at risk EG0021 affected189 at risk
Vertigo positional	Ear and labyrinth disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Coronary artery disease	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0002 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Acute myocardial infarction	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Angina pectoris	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Bundle branch block right	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Cardiac failure	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Cardiac failure congestive	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Cor pulmonale	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Supraventricular tachycardia	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Tachycardia	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Hypertensive emergency	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Orthostatic hypotension	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Peripheral arterial occlusive disease	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Peripheral artery stenosis	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Thrombophlebitis migrans	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Venous thrombosis	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Abdominal pain	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0012 affected186 at risk EG0020 affected189 at risk
Diarrhoea	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Gastric ulcer	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Pancreatitis acute	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Small intestinal obstruction	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Umbilical hernia	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Neuropathic arthropathy	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0021 affected189 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Acute prerenal failure	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Renal colic	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Renal failure acute	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Renal impairment	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Concussion	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0010 affected186 at risk EG0021 affected189 at risk
Humerus fracture	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0001 affected188 at risk EG0010 affected186 at risk EG0020 affected189 at risk
Wound	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk
Vitrectomy	Surgical and medical procedures	MEDDRA 16.0	Systematic Assessment	EG0000 affected188 at risk EG0011 affected186 at risk EG0020 affected189 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG00040 affected188 at risk EG00134 affected186 at risk EG00227 affected189 at risk
Urinary tract infection	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG00023 affected188 at risk EG00124 affected186 at risk EG00224 affected189 at risk
Influenza	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG00012 affected188 at risk EG0017 affected186 at risk EG00214 affected189 at risk
Bronchitis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG00012 affected188 at risk EG00110 affected186 at risk EG0028 affected189 at risk
Gastroenteritis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG00010 affected188 at risk EG0018 affected186 at risk EG0021 affected189 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG000111 affected188 at risk EG00197 affected186 at risk EG002110 affected189 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG00014 affected188 at risk EG0016 affected186 at risk EG0027 affected189 at risk
Dizziness	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0002 affected188 at risk EG0015 affected186 at risk EG00213 affected189 at risk
Headache	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0009 affected188 at risk EG0018 affected186 at risk EG00211 affected189 at risk
Hypertension	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG00010 affected188 at risk EG0019 affected186 at risk EG0027 affected189 at risk
Diarrhoea	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG00017 affected188 at risk EG00112 affected186 at risk EG00217 affected189 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG00010 affected188 at risk EG00118 affected186 at risk EG00211 affected189 at risk
Back pain	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG00014 affected188 at risk EG00112 affected186 at risk EG00215 affected189 at risk

Ancestor Terms

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D001835	Body Weight
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

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	Hypothesis test: H0: No difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 10 mg and placebo Ha: A difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 10 mg and placebo	ANCOVA	Model - Covariates: baseline insulin daily dose,baseline HbA1c Fixed effects: baseline eGFR, region, baseline background medication, treatment	0.004	Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in insulin dose at week 52 was the second step in hierarchical sequence.	Adjusted mean difference	-8.83	Standard Error of the Mean	3.05	2-Sided	97.5	-15.69	-1.97			Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo	No	Superiority or Other
OG000 OG002	Hypothesis test: H0: No difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 25 mg and placebo Ha : A difference in change from baseline to Week 52 in insulin dose (IU/day) between Empagliflozin 25 mg and placebo	ANCOVA	Model - Covariates: baseline insulin daily dose,baseline HbA1c Fixed effects: baseline eGFR, region, baseline background medication, treatment	0.0003	Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in insulin dose at week 52 was the second step in hierarchical sequence.	Adjusted mean difference	-11.22	Standard Error of the Mean	3.05	2-Sided	97.5	-18.09	-4.36			Estimated value = Adjusted mean of Empagliflozin 25 mg - Adjusted mean of placebo.	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	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Hypothesis test: H0: No difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 10 mg and placebo Ha : A difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 10 mg and placebo	ANCOVA	Model includes baseline weight, baseline HbA1c as covariates and baseline eGFR, region, baseline background medication, treatment as fixed effects.	<0.0001	Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in body weight at week 52 was the third step in hierarchical sequence.	Adjusted mean difference	-2.39	Standard Error of the Mean	0.51	2-Sided	97.5	-3.54	-1.24			Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo	No	Superiority or Other
OG000 OG002	hypothesis test: H0: No difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 25 mg and placebo Ha: A difference in change from baseline to Week 52 in body weight (kg) between Empagliflozin 25 mg and placebo	ANCOVA	Model includes baseline weight, baseline HbA1c as covariates and baseline eGFR, region, baseline background medication, treatment as fixed effects.	<0.0001	Hierarchical testing adjusted for multiple comparisons within each dose level, alpha split equally between the doses (2.5%). Empagliflozin versus placebo change from baseline in body weight at week 52 was the third step in hierarchical sequence.	Adjusted mean difference	-2.48	Standard Error of the Mean	0.51	2-Sided	97.5	-3.63	-1.33			Estimated value = Adjusted mean of empagliflozin 25 mg - Adjusted mean of placebo	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	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	H0: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 10 mg and placebo >0.3 Ha: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 10 mg and placebo ≤0.3	ANCOVA	Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.	<0.0001	Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).	Adjusted mean difference	-0.38	Standard Error of the Mean	0.11	2-Sided	97.5	-0.62	-0.13	Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo	Yes	Non-Inferiority or Equivalence	The non- inferiority margin was 0.3%, one-sided.
OG000 OG001	Hypothesis test: H0: No difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 10 mg and placebo Ha : A difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 10 mg and placebo	ANCOVA	Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.	0.0005	Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).	Adjusted mean difference	-0.38	Standard Error of the Mean	0.11	2-Sided	97.5	-0.62	-0.13	Estimated value = Adjusted mean of empagliflozin 10 mg - Adjusted mean of placebo	No	Superiority or Other
OG000 OG002	H013: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 25 mg and placebo >0.3 Ha13: Difference in change from baseline to Week 52 in HbA1c (%) between empagliflozin 25 mg and placebo ≤0.3	ANCOVA	Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.	<0.0001	Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).	Adjusted mean difference	-0.46	Standard Error of the Mean	0.11	2-Sided	97.5	-0.70	-0.22	Estimated value = Adjusted mean of empagliflozin 25 mg - Adjusted mean of placebo	Yes	Non-Inferiority or Equivalence	The non- inferiority margin was 0.3%, one-sided.
OG000 OG002	Hypothesis test: H0: No difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 25 mg and placebo Ha : A difference in change from baseline to Week 52 in HbA1c (%) between Empagliflozin 25 mg and placebo	ANCOVA	Model includes baseline HbA1c as covariate and baseline eGFR, geographical region, baseline background medication, treatment as fixed effects.	<0.0001	Hierarchical testing adjusted for multiple comparisons within each dose, alpha split between the doses (2.5%). Empagliflozin versus placebo change from baseline in HbA1c at week 52 was the 4th step (non-inferiority) and 5th step (superiority).	Adjusted mean difference	-0.46	Standard Error of the Mean	0.11	2-Sided	97.5	-0.70	-0.22	Estimated value = Adjusted mean of empagliflozin 25 mg - Adjusted mean of placebo	No	Superiority or Other

ID	Term
D003924	Diabetes Mellitus, Type 2
D009765	Obesity