Efficacy and Safety of Empagliflozin (BI 10773) / Linagli... | NCT01422876

ID	Type	Description	Link
2011-000383-10	EudraCT Number	EudraCT

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
BI 10773/linagliptin FDC (high dose)	Experimental	Patients receive BI 10773/linagliptin FDC (high dose) once daily	Drug: high dose FDC Drug: low dose FDC placebo Drug: high dose BI 10773 placebo Drug: BI 10773 low dose placebo Drug: linagliptin placebo
BI 10773/linagliptin FDC (low dose)	Experimental	Patients receive BI 10773/linagliptin FDC (low dose) once daily	Drug: high dose FDC placebo Drug: low dose FDC Drug: high dose BI 10773 placebo Drug: BI 10773 low dose placebo Drug: linagliptin placebo
BI 10773 (high dose)	Active Comparator	Patients receive BI 10773 (high dose) once daily	Drug: BI 10773 high dose Drug: high dose FDC placebo Drug: low dose FDC placebo Drug: low dose BI 10773 placebo Drug: linagliptin placebo
BI 10773 (low dose)	Active Comparator	Patients receive BI 10773 (low dose) once daily	Drug: high dose FDC placebo Drug: low dose FDC placebo Drug: high dose BI 10773 placebo Drug: BI 10773 low dose Drug: linagliptin placebo
Linagliptin

Name	Type	Description	Arm Group Labels	Other Names
high dose FDC	Drug	once daily	BI 10773/linagliptin FDC (high dose)

Measure	Description	Time Frame
Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients	Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage.	Baseline and 24 weeks
Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients	Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage.	Baseline and 24 weeks

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients	Change from baseline in fasting plasma glucose at week 24 for Metformin Background patients.	Baseline and 24 Weeks
Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1275.1.01103 Boehringer Ingelheim Investigational Site		Birmingham	Alabama		United States
1275.1.01107 Boehringer Ingelheim Investigational Site

PubMed Identifier	Type	Citation	Retractions
29949041	Derived	DeFronzo RA, Lee C, Kohler S. Safety and Tolerability of Combinations of Empagliflozin and Linagliptin in Patients with Type 2 Diabetes: Pooled Data from Two Randomized Controlled Trials. Adv Ther. 2018 Jul;35(7):1009-1022. doi: 10.1007/s12325-018-0724-y. Epub 2018 Jun 15.
25633662	Derived	Lewin A, DeFronzo RA, Patel S, Liu D, Kaste R, Woerle HJ, Broedl UC. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes. Diabetes Care. 2015 Mar;38(3):394-402. doi: 10.2337/dc14-2365. Epub 2015 Jan 29.

ID	Title	Description
FG000	Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin: Oral

Arm/Group Information

ID	Title	Description
BG000	Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. . Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
BG001	Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
BG002	Metformin Background: Empagliflozin 25 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral
BG003	Metformin Background: Empagliflozin 10 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral
BG004	Metformin Background: Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation and treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral
BG005	Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
BG006	Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
BG007	Treatment Naive: Empagliflozin 25 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral
BG008	Treatment Naive: Empagliflozin 10 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral
BG009	Treatment Naive: Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral
BG010	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

Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients

Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage.

Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.

Posted

Least Squares Mean

Standard Error

% change from baseline

Baseline and 24 weeks

ID	Title	Description
OG000	Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
OG002	Metformin Background: Empagliflozin 25 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral
OG003	Metformin Background: Empagliflozin 10 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral
OG004	Metformin Background: Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral

Units	Counts
Participants	OG000134 OG001135 OG002140 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.19± 0.06 OG001-1.08± 0.06 OG002-0.62± 0.06 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 OG002	Model for Week 24 includes baseline HbA1c (p<0.0001) as linear covariate(s) and baseline eGFR (MDRD) (p=0.0038), geographical region (p<0.0001), treatment (p<0.0001) as fixed effect(s).	ANCOVA		<0.0001		Mean Difference (Net)	-0.58	Standard Error of the Mean	0.09	2-Sided	95	-0.75	-0.41				No	Superiority or Other
OG000

Secondary

Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients

Change from baseline in fasting plasma glucose at week 24 for Metformin Background patients.

Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.

Posted

Least Squares Mean

Standard Error

mg/dL change from baseline

Baseline and 24 Weeks

ID	Title	Description
OG000	Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
OG002	Metformin Background: Empagliflozin 25 mg

Secondary

Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients

Change from baseline in fasting plasma glucose at week 24 for Treatment Naive patients.

Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.

Posted

Least Squares Mean

Standard Error

mg/dL change from baseline

Baseline and 24 Weeks

ID	Title	Description
OG000	Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
OG002	Treatment Naive: Empagliflozin 25 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Secondary

Change From Baseline in Body Weight for Metformin Background Patients

Change from baseline in body weight for Metformin Background patients.

Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all Metformin Background patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.

Posted

Least Squares Mean

Standard Error

kg change from baseline

Baseline and 24 Weeks

ID	Title	Description
OG000	Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
OG002	Metformin Background: Empagliflozin 25 mg

Primary

Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients

Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised to and treated who had a baseline and at least 1 on treatment HbA1c value.

Posted

Least Squares Mean

Standard Error

% change from baseline

Baseline and 24 weeks

ID	Title	Description
OG000	Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
OG002	Treatment Naive: Empagliflozin 25 mg

Secondary

Change From Baseline in Body Weight for Treatment Naive Patients

Change from baseline in body weight for Treatment Naive patients.

Full Analysis Set (FAS) with last observation carried forward (LOCF). FAS - all treatment naive patients randomised and treated who had a baseline and at least 1 on treatment HbA1c value.

Posted

Least Squares Mean

Standard Error

kg change from baseline

Baseline and 24 Weeks

ID	Title	Description
OG000	Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
OG002	Treatment Naive: Empagliflozin 25 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral

Secondary

Occurrence of Treat to Target Efficacy Response for Metformin Background Patients

Occurrence of the treat-to-target efficacy response for Metformin Background patients measured as HbA1c < 7.0% after 24 weeks of treatment for patients with HbA1c >=7.0% at baseline.

Full Analysis Set (FAS) with non-completers considered failures (NCF). FAS- Metformin background patients randomised and treated who had a baseline (HbA1c>= 7% at baseline are included) and at least 1 on treatment HbA1c value with NCF approach, in which missing data due to premature discontinuation of a patient were considered as failure.

Posted

Number

95% Confidence Interval

% of patients satisfying HbA1c <7.0%

24 Weeks

ID	Title	Description
OG000	Metformin Background: Empagliflozin 25 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Metformin Background: Empagliflozin 10 mg/Linagliptin 5 mg	Study population on a stable background of metformin defined as pre-treated with metformin (≥1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral

Secondary

Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients

Occurrence of the treat-to-target efficacy response for Treatment Naive patients measured as HbA1c < 7.0% after 24 weeks of treatment for patients with HbA1c >=7.0% at baseline.

Full Analysis Set (FAS) with non-completers considered failures (NCF). FAS-treatment naive patients randomised and treated who had a baseline (HbA1c>= 7% at baseline are included) and at least 1 on treatment HbA1c value with NCF approach, in which missing data due to premature discontinuation of a patient were considered as failure.

Posted

Number

95% Confidence Interval

% of patients satisfying HbA1c <7.0%

24 Weeks

ID	Title	Description
OG000	Treatment Naive: Empagliflozin 25 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral
OG001	Treament Naive: Empagliflozin 10 mg/Linagliptin 5 mg	Study population treatment naive defined as an absence of any oral antidiabetic therapy, GLP-1 analog or insulin for 12 weeks prior to randomisation. Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral
OG002

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bacterial infection	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG0030 affected275 at risk EG0041 affected267 at risk
Cellulitis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Cystitis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Diverticulitis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Encephalitis viral	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Meningitis tuberculous	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Peritonitis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Pneumonia viral	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Pyelonephritis acute	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Pyelonephritis chronic	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Tooth abscess	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Urinary tract infection	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Urosepsis	Infections and infestations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Adenoid cystic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Clear cell renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Gastrointestinal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Metastases to peritoneum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Non-small cell lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Ovarian cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Renal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Alkalosis	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Dehydration	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Confusional state	Psychiatric disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Mental status changes	Psychiatric disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Transient ischaemic attack	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Brain oedema	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Cerebral infarction	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Cerebrovascular accident	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Dementia Alzheimer's type	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Encephalopathy	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Haemorrhagic stroke	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Lethargy	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Syncope	Nervous system disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Acute coronary syndrome	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Angina pectoris	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Angina unstable	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Coronary artery disease	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Coronary artery occlusion	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Hypertensive heart disease	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Myocardial infarction	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Palpitations	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Silent myocardial infarction	Cardiac disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Hypotension	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Varicose vein	Vascular disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Abdominal adhesions	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Abdominal pain	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Abdominal strangulated hernia	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Colitis ischaemic	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Mechanical ileus	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Pancreatitis chronic	Gastrointestinal disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0022 affected276 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Hepatic mass	Hepatobiliary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Diabetic foot	Skin and subcutaneous tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Myofascial pain syndrome	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0021 affected276 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Calculus bladder	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0001 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Calculus ureteric	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Hydronephrosis	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Renal colic	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Renal failure acute	Renal and urinary disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Postmenopausal haemorrhage	Reproductive system and breast disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Rectocele	Reproductive system and breast disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Chest pain	General disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0012 affected272 at risk EG0021 affected276 at risk EG003
Non-cardiac chest pain	General disorders	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Troponin increased	Investigations	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Chemical injury	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Fibula fracture	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0020 affected276 at risk EG003
Seroma	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0011 affected272 at risk EG0020 affected276 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 at risk EG003
Finger amputation	Surgical and medical procedures	MEDDRA 16.0	Systematic Assessment	EG0000 affected273 at risk EG0010 affected272 at risk EG0021 affected276 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
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D011799	Quinazolines

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Empagliflozin 25 mg/Linagliptin 5 mg	Test product: Empagliflozin/linagliptin FDC tablets dose: 25 mg/5 mg q.d. mode of admin.: Oral	12	273	80	273
EG001	Empagliflozin 10 mg/Linagliptin 5 mg	Test product: Empagliflozin/linagliptin FDC tablets dose: 10 mg/5 mg q.d. mode of admin.: Oral	16	272	86	272
EG002	Empagliflozin 25 mg	Reference therapy 1: Empagliflozin tablets dose: 25 mg q.d. mode of admin.: Oral	19	276	70	276
EG003	Empagliflozin 10 mg	Reference therapy 1: Empagliflozin tablets dose: 10 mg q.d. mode of admin.: Oral	16	275	83	275
EG004	Linagliptin 5 mg	Reference therapy 2: Linagliptin tablets dose: 5 mg q.d. mode of admin.: Oral	10	267	94	267