Trial Outcomes & Findings for A Study to Test How Well Empagliflozin Works in Japanese People With Type 2 Diabetes Who Are Older Than 65 Years (NCT NCT04531462)

NCT ID: NCT04531462

Last Updated: 2024-05-02

Results Overview

Change in glycated hemoglobin (HbA1c) (in units of %) from baseline after 52 weeks of treatment was modelled using a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) which included fixed classification effects for treatment, gender, baseline renal function, visit and visit-by-treatment interaction, and a linear covariate for baseline HbA1c and age. The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.The Least Squares Mean (Standard Error) after 52 weeks of treatment is reported.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 129 participants
• Primary outcome timeframe: Change in HbA1c from baseline after 52 weeks of treatment was calculated using the MMRM model which is a longitudinal analyses and it incorporates HbA1c values from baseline and after 4 weeks, 12 weeks, 24 weeks, 36 weeks and 52 weeks of treatment.
• Results posted on: 2024-05-02

Participant Flow

This randomised, double-blind, placebo-controlled, parallel group, multicentre trial compared 10 mg empagliflozin with placebo after 52 weeks in elderly Japanese patients with Type 2 diabetes mellitus (T2DM) and insufficient glycaemic control.

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Measure	Placebo Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Overall Study STARTED	64	65
Overall Study COMPLETED	58	61
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Measure	Placebo Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Overall Study Withdrawal by Subject	3	1
Overall Study Adverse Event	3	3

Baseline Characteristics

A Study to Test How Well Empagliflozin Works in Japanese People With Type 2 Diabetes Who Are Older Than 65 Years

Baseline characteristics by cohort

Measure	Placebo n=63 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=64 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.	Total n=127 Participants Total of all reporting groups
Age, Continuous	74.0 years STANDARD_DEVIATION 5.1 • n=5 Participants	74.2 years STANDARD_DEVIATION 4.9 • n=7 Participants	74.1 years STANDARD_DEVIATION 5.0 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	16 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	48 Participants n=7 Participants	92 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=5 Participants	64 Participants n=7 Participants	127 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	63 Participants n=5 Participants	64 Participants n=7 Participants	127 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Percentage of glycated haemoglobin (HbA1c)	7.6 Percentage of glycated haemoglobin STANDARD_DEVIATION 0.5 • n=5 Participants	7.6 Percentage of glycated haemoglobin STANDARD_DEVIATION 0.5 • n=7 Participants	7.6 Percentage of glycated haemoglobin STANDARD_DEVIATION 0.5 • n=5 Participants

PRIMARY outcome

Timeframe: Change in HbA1c from baseline after 52 weeks of treatment was calculated using the MMRM model which is a longitudinal analyses and it incorporates HbA1c values from baseline and after 4 weeks, 12 weeks, 24 weeks, 36 weeks and 52 weeks of treatment.

Population: Full Analysis Set (Observed cases): This set included all patients randomised, treated with at least one dose of trial medication, and with a baseline and at least one on-treatment HbA1c value. Only the available data that were observed while the patients were on treatment were analysed.

Change in glycated hemoglobin (HbA1c) (in units of %) from baseline after 52 weeks of treatment was modelled using a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) which included fixed classification effects for treatment, gender, baseline renal function, visit and visit-by-treatment interaction, and a linear covariate for baseline HbA1c and age. The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.The Least Squares Mean (Standard Error) after 52 weeks of treatment is reported.

Outcome measures

Measure	Placebo n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=64 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change in HbA1c From Baseline After 52 Weeks of Treatment	-0.12 percentage of glycated hemoglobin Standard Error 0.08	-0.69 percentage of glycated hemoglobin Standard Error 0.07

SECONDARY outcome

Timeframe: At baseline and at Week 52

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

Muscle mass was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of muscle mass from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline muscle mass, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=59 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Muscle Mass From Baseline to Week 52	-0.96 kilogram Standard Error 0.36	-1.57 kilogram Standard Error 0.35

SECONDARY outcome

Timeframe: At baseline and at Week 52

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

Body fat mass was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of body fat measurement from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline body fat measurement, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=59 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Body Fat Measurement From Baseline to Week 52	0.08 kilogram Standard Error 0.29	-1.77 kilogram Standard Error 0.28

SECONDARY outcome

Timeframe: At baseline and at Week 52.

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

Lean body mass (fat-free mass) was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of lean body mass from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline lean body mass, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=59 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Lean Body Mass From Baseline to Week 52	-1.08 kilogram Standard Error 0.27	-1.61 kilogram Standard Error 0.26

SECONDARY outcome

Timeframe: At baseline and at Week 52.

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

Total body water was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of total body water from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline total body water, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=59 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Total Body Water From Baseline to Week 52	-0.72 kilogram Standard Error 0.21	-1.35 kilogram Standard Error 0.21

SECONDARY outcome

Timeframe: At baseline and at Week 52.

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

Bone mineral content (estimated bone mass) was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of bone mineral content from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline bone mineral content, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=59 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Bone Mineral Content From Baseline to Week 52	-0.06 kilogram Standard Error 0.02	-0.09 kilogram Standard Error 0.01

SECONDARY outcome

Timeframe: At baseline and at Week 52.

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

Skeletal muscle index is calculated by dividing the limb muscle mass (kg) by the square of the height (m2).

The limb muscle mass was estimated via bioelectrical impedance analysis (BIA) which is a commonly used method for estimating body composition, and it assesses body composition by passing a very small current through the body and assessing differences in impedance caused by the fact that fat and lean tissues have different electrical properties. To measure the body composition the patient barefoot stood on the bench evenly on the toe and heel electrodes and held the grip on each hand.

Change of skeletal muscle index from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline skeletal muscle index, age, baseline glycated hemoglobin (HbA1c), baseline body mass index as linear covariates and sex, treatment as fixed effects.

"Baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=57 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Skeletal Muscle Index From Baseline to Week 52	-0.245 kilogram/meter^2 (kg/m^2) Standard Error 0.064	-0.326 kilogram/meter^2 (kg/m^2) Standard Error 0.062

SECONDARY outcome

Timeframe: At baseline and at Week 52.

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

A Smedley-type dynamometer was used to measure grip strength. The site staff instructed the patient to adjust the grip width so that the second joint of the index finger is approximately 90 degrees (almost right angle). The site staff asked the patient to be careful not to touch the body or clothes with hand while keeping arms down naturally. The site staff made sure that the patient does not wave the grip dynamometer. Grip strength was measured twice alternately left and right.

Change of grip strength from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline grip strength, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=59 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Grip Strength From Baseline to Week 52	-0.6 kilogram Standard Error 0.3	-0.9 kilogram Standard Error 0.3

SECONDARY outcome

Timeframe: At baseline and at Week 52.

Population: Treated set (Observed cases, including values after rescue (OC-IR)): All patients randomized and treated with at least one dose of trial medication. Values measured after rescue medication were also used. Patients with missing values at Week 52 or at baseline were not included in the analysis.

For the stand test patients fold their arms across their chest and try to stand up once from a chair. If patients can stand from a chair, they repeat same action five times. It is measured the time required to perform five rise from a chair to an upright position as fast as possible without the use of arms.

Change of time in the 5-time chair stand test from baseline to Week 52 was modelled using an Analysis of Covariance (ANCOVA) which included baseline 5-time chair stand test, age, baseline glycated hemoglobin (HbA1c), baseline body mass index (BMI) as linear covariates and sex, treatment as fixed effects.

The term "baseline" refers to the last observed measurement prior to the administration of any randomised trial medication.

Outcome measures

Measure	Placebo n=58 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10 mg n=62 Participants Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Change of Time in the 5-time Chair Stand Test From Baseline to Week 52	-0.9 seconds Standard Error 0.3	-0.9 seconds Standard Error 0.3

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 13 other events

Deaths: 1 deaths

Empagliflozin 10mg

Serious events: 8 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=64 participants at risk Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10mg n=65 participants at risk Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Eye disorders Cataract	1.6% 1/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Eye disorders Exfoliation glaucoma	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Eye disorders Glaucoma	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Gastrointestinal disorders Duodenal polyp	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
General disorders Death	1.6% 1/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Infections and infestations Hepatitis E	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Injury, poisoning and procedural complications Brain contusion	1.6% 1/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Injury, poisoning and procedural complications Femoral neck fracture	3.1% 2/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Injury, poisoning and procedural complications Rib fracture	1.6% 1/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Injury, poisoning and procedural complications Traumatic haemothorax	1.6% 1/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Musculoskeletal and connective tissue disorders Exostosis	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Nervous system disorders Embolic stroke	0.00% 0/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	1.5% 1/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Nervous system disorders Facial paralysis	1.6% 1/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Nervous system disorders Optic neuritis	1.6% 1/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.

Other adverse events

Measure	Placebo n=64 participants at risk Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet of placebo matching empagliflozin in addition to the standard of care treatment	Empagliflozin 10mg n=65 participants at risk Type 2 diabetes mellitus (T2DM) Japanese patients older than 65 years administered orally once daily one film-coated tablet 10 milligram (mg) of empagliflozin in addition to the standard of care treatment.
Gastrointestinal disorders Constipation	4.7% 3/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	10.8% 7/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Gastrointestinal disorders Diarrhoea	6.2% 4/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	0.00% 0/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
General disorders Pyrexia	4.7% 3/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	6.2% 4/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.
Infections and infestations Nasopharyngitis	6.2% 4/64 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.	4.6% 3/65 • From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days. Treated set: All patients randomized and treated with at least one dose of trial medication.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

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