NCT04531462

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

Completed Phase 4 Results posted Last updated 2 May 2024

What this trial tests

Phase 4 trial testing Empagliflozin in Diabetes Mellitus, Type 2 in 129 participants. Completed in 26 August 2022.

Timeline

5 October 2020

Primary endpoint
19 August 2022

26 August 2022

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	129
Start date	5 October 2020
Primary completion	19 August 2022
Estimated completion	26 August 2022
Sites	18 locations across Japan

Drugs / interventions tested

• Empagliflozin (empagliflozin) — full drug profile →
• Placebo

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

65 and older, any sex, with Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in HbA1c From Baseline After 52 Weeks of Treatment Primary · 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.

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.

Group	Value	95% CI
Placebo	-0.12	± 0.08
Empagliflozin 10 mg	-0.69	± 0.07

Change of Muscle Mass From Baseline to Week 52 Secondary · At baseline and at Week 52

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 bas

Group	Value	95% CI
Placebo	-0.96	± 0.36
Empagliflozin 10 mg	-1.57	± 0.35

Change of Body Fat Measurement From Baseline to Week 52 Secondary · At baseline and at Week 52

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 in

Group	Value	95% CI
Placebo	0.08	± 0.29
Empagliflozin 10 mg	-1.77	± 0.28

Change of Lean Body Mass From Baseline to Week 52 Secondary · At baseline and at Week 52.

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 (ANCO

Group	Value	95% CI
Placebo	-1.08	± 0.27
Empagliflozin 10 mg	-1.61	± 0.26

Change of Total Body Water From Baseline to Week 52 Secondary · At baseline and at Week 52.

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 in

Group	Value	95% CI
Placebo	-0.72	± 0.21
Empagliflozin 10 mg	-1.35	± 0.21

Change of Bone Mineral Content From Baseline to Week 52 Secondary · At baseline and at Week 52.

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 o

Group	Value	95% CI
Placebo	-0.06	± 0.02
Empagliflozin 10 mg	-0.09	± 0.01

Change of Skeletal Muscle Index From Baseline to Week 52 Secondary · At baseline and at Week 52.

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. C

Group	Value	95% CI
Placebo	-0.245	± 0.064
Empagliflozin 10 mg	-0.326	± 0.062

Change of Grip Strength From Baseline to Week 52 Secondary · At baseline and at Week 52.

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 includ

Group	Value	95% CI
Placebo	-0.6	± 0.3
Empagliflozin 10 mg	-0.9	± 0.3

Change of Time in the 5-time Chair Stand Test From Baseline to Week 52 Secondary · At baseline and at Week 52.

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

Group	Value	95% CI
Placebo	-0.9	± 0.3
Empagliflozin 10 mg	-0.9	± 0.3

Adverse events — posted to ClinicalTrials.gov

Time frame: From the administration of first dose of randomised trial medication until treatment stop +7 days of residual effect period, up to 378 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 8/64 (13%)

Deaths: 1/64

Empagliflozin 10mg

Serious: 8/65 (12%)

Deaths: 0/65

Serious adverse events (17 terms)

Reaction	System	Placebo	Empagliflozin 10mg
Femoral neck fracture	Injury, poisoning and procedural complications	—	—
Atrial fibrillation	Cardiac disorders	—	—
Cataract	Eye disorders	—	—
Exfoliation glaucoma	Eye disorders	—	—
Glaucoma	Eye disorders	—	—
Duodenal polyp	Gastrointestinal disorders	—	—
Death	General disorders	—	—
Hepatic function abnormal	Hepatobiliary disorders	—	—
Hepatitis E	Infections and infestations	—	—
Brain contusion	Injury, poisoning and procedural complications	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—
Traumatic haemothorax	Injury, poisoning and procedural complications	—	—
Exostosis	Musculoskeletal and connective tissue disorders	—	—
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Embolic stroke	Nervous system disorders	—	—
Facial paralysis	Nervous system disorders	—	—
Optic neuritis	Nervous system disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Placebo	Empagliflozin 10mg
Constipation	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Nasopharyngitis	Infections and infestations	—	—

Most-reported serious reactions: Femoral neck fracture, Atrial fibrillation, Cataract, Exfoliation glaucoma, Glaucoma, Duodenal polyp, Death, Hepatic function abnormal.

Data from ClinicalTrials.gov NCT04531462 adverse events section.

Sponsor's own description

This study is to assess the efficacy of empagliflozin 10 mg after 52 weeks compared to placebo in elderly patients with Type 2 diabetes mellitus (T2DM) and to explore if empagliflozin has any impact on patient physical condition compared to placebo in elderly patients with T2DM.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Functional and Clinical Importance of SGLT2-inhibitors in Frailty: From the Kidney to the Heart.
   Santulli G, Varzideh F, Forzano I, Wilson S, et al · · 2023 · cited 50× · PMID 37403685 · DOI 10.1161/hypertensionaha.123.20598
2. Rationale and design of the EMPA-ELDERLY trial: a randomised, double-blind, placebo-controlled, 52-week clinical trial of the efficacy and safety of the sodium-glucose cotransporter-2 inhibitor empagliflozin in elderly Japanese patients with type 2 diabetes.
   Yabe D, Shiki K, Suzaki K, Meinicke T, et al · · 2021 · cited 20× · PMID 33827843 · DOI 10.1136/bmjopen-2020-045844
3. Long-term effects of SGLT2 inhibitors on arrhythmias: a systematic review and meta-analysis.
   Li P, Chen W, Chen R, Zhang H, et al · · 2025 · cited 1× · PMID 40672365 · DOI 10.3389/fphar.2025.1558367