Diabetes Mellitus, Type 2
Conditions
Brief summary
To monitor the safety profile and effectiveness of JARDIANCE DUO® in Korean patients with type 2 diabetes mellitus in a routine clinical practice setting
Interventions
DRUGJARDIANCE DUO®
empagliflozin and metformin
Sponsors
Boehringer Ingelheim
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have started at first time on JARDIANCE DUO® in accordance with the approved label in Korea * Age ≥19 years at enrolment * Patients who have signed on the data release consent form
Exclusion criteria
* Patients with previous exposure to JARDIANCE®, JARDIANCE DUO® * Hypersensitivity to active ingredients empagliflozin and/or metformin or to any of the excipients * Moderate (stage 3b) and severe renal failure (CrCl \< 45 ml/min or eGFR \< 45 ml/min/1.73 square meter) * Acute conditions with the potential to alter renal function such as: dehydration, severe infection, cardiovascular collapse (shock), acute myocardial infarction, sepsis * Type1 diabetes, acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma, history of a ketoacidosis (type 1 diabetes and diabetic ketoacidosis should be treated with insulin). * Congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure * Radiologic studies involving the use of intravascular iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials) * Intravascular administration of iodinated contrast media may lead to acute renal failure and has been associated with lactic acidosis in patients receiving metformin. Therefore, in patients with eGFR \> 60ml/min/1.73m2, JARDIANCE DUO® must be discontinued prior to, or at the time of the test and not be reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and has not deteriorated further. In patients with moderate renal impairment (eGFR 45-60 ml/min/1.73m2), JARDIANCE DUO® must be discontinued 48 hours before administration of iodinated contrast media and not be reinstituted until at least 48 hours afterwards, and only after renal function has been re-evaluated and has not deteriorated further. * In patients with severe infections or severe traumatic systemic disorders, JARDIANCE DUO® should be temporarily suspended, and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal. * JARDIANCE DUO® should be temporarily suspended for any surgical procedure(except minor procedures not associated with restricted intake of food and fluids)before 48 hours, and not be reinstituted until 48 hours afterwards, after renal function has been evaluated as normal. * Patients with malnutrition, starvation, hypostheniam pituitary or adrenal insufficiency * Impaired hepatic function (since impaired hepatic function has been associated with some cases of lactic acidosis, JARDIANCE DUO® should generally be avoided in patients with clinical or laboratory evidence of hepatic disease), pulmonary infarction, severe respiratory impairment, any condition associated with hypoxemia, excessive alcohol intake, GI disorders such as dehydration, diarrhoea or vomiting * Pregnant women, women who may be pregnant, nursing women * Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction, shock * Current participation in other clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Any Adverse Events | From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days. | Percentage of participants with any adverse events was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method. |
| Percentage of Participants With Adverse Events Relating to Study Drug | From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days. | Percentage of participants with adverse events relating to study drug was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method. |
| Percentage of Participants With Unexpected Adverse Events | From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days. | Percentage of participants with unexpected adverse events was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method. |
| Percentage of Participants With Adverse Events of Special Interest | From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days. | Percentage of participants with adverse events of special interest was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method. |
| Percentage of Participants With Adverse Events Leading to Discontinuation of the Drug | From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days. | Percentage of participants with adverse events leading to discontinuation of the drug was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Systolic Blood Pressure (SBP) at Last Visit From Baseline | At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Change in the systolic blood pressure (SBP) at Last Visit from baseline was reported. |
| Change in the Glycosylated Hemoglobin (HbA1c) at Last Visit From Baseline | At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Change in the glycosylated hemoglobin (HbA1c) at Last Visit from baseline was reported. |
| Number of Participants Per Final Effectiveness Assessment Category at Last Visit | At last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Number of participants per final effectiveness assessment category at Last Visit was reported. The final effectiveness consisted of 4 categories: Improved (If determined as there was any effect of maintaining or improving disease related factors.), Unchanged (If disease related factors had not been changed compared with before administration, and not determined as there was any effect of maintaining symptoms.), Aggravated (If disease related factors were worse than before administration.), and Unassessable (If it cannot be determined due to insufficient information collected.). |
| Change in the Diastolic Blood Pressure (DBP) at Last Visit From Baseline | At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Change in the diastolic blood pressure (DBP) at Last Visit from baseline was reported. |
| Number of Participants Reached Target Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c < 7%) at Last Visit | At last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Number of participants reached target effectiveness response in the glycosylated hemoglobin (HbA1c) (HbA1c \< 7%) at Last Visit was reported. Target effectiveness response in the glycosylated hemoglobin (HbA1c) was defined as HbA1c less than 7%. |
| Number of Participants With Relative Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c Decrease of 0.5% Comparing to Baseline) at Last Visit | At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Number of participants with relative effectiveness response in the glycosylated hemoglobin (HbA1c) at Last Visit was reported. Relative effectiveness response in the glycosylated hemoglobin (HbA1c) at last visit was defined as HbA1c decrease of 0.5% or more at the last visit comparing to baseline. |
| Change in the Fasting Plasma Glucose (FPG) at Last Visit From Baseline | At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Change in the Fasting Plasma Glucose (FPG) at Last Visit from baseline was reported. |
| Change in the Body Weight at Last Visit From Baseline | At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline). | Change in the body weight at Last Visit from baseline was reported. |
Countries
South Korea
Participant flow
Recruitment details
This post-marketing surveillance study re-examined case report forms retrieving at 20 sites from 21 January 2016 till 11 August 2020 for subjects who had Type 2 Diabetes Mellitus, and were initially administered Jardiance Duo® following the study start date investigating factors affecting the safety and effectiveness of study drug.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) All subjects who had Type 2 Diabetes Mellitus (T2DM), were initially administered orally various dosages of Jardiance Duo® tablet (Jardiance Duo® (empagliflozin/metformin) tablet dosages: 5/500 milligrams (mg), 5/850 mg, 5/1000 mg, 12.5/500 mg, 12.5/850 mg, 12.5/1000 mg) following the baseline (Visit 1) for an administration for 24 weeks, and with the case report forms (CRFs) retrieving at 20 sites from 21 January 2016 till 11 August 2020. Each patient was planned to be visited once at baseline (Visit 1), followed by 2 planned follow-up visits at Week 12 (after 12 weeks of medication administration) and at Week 24 (after 24 weeks of medication administration). | 620 |
| Total | 620 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inclusion/exclusion criteria violation | 33 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Taken study drug prior to contract date | 3 |
Baseline characteristics
| Characteristic | JARDIANCE DUO® (Empagliflozin/Metformin) | — |
|---|---|---|
| Age, Continuous | 56.39 Years STANDARD_DEVIATION 12.78 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 221 Participants | — |
| Sex: Female, Male Male | 399 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 620 |
| other Total, other adverse events | 0 / 620 |
| serious Total, serious adverse events | 10 / 620 |
Outcome results
Primary
Percentage of Participants With Adverse Events Leading to Discontinuation of the Drug
Percentage of participants with adverse events leading to discontinuation of the drug was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.
Time frame: From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Population: Safety analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo® once at least, and were followed up by the physician once or more.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Percentage of Participants With Adverse Events Leading to Discontinuation of the Drug | 2.90 Percentage of participants |
Primary
Percentage of Participants With Adverse Events of Special Interest
Percentage of participants with adverse events of special interest was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.
Time frame: From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Population: Safety analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo® once at least, and were followed up by the physician once or more.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Percentage of Participants With Adverse Events of Special Interest | 0.65 Percentage of participants |
Primary
Percentage of Participants With Adverse Events Relating to Study Drug
Percentage of participants with adverse events relating to study drug was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.
Time frame: From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Population: Safety analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo® once at least, and were followed up by the physician once or more.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Percentage of Participants With Adverse Events Relating to Study Drug | 5.48 Percentage of participants |
Primary
Percentage of Participants With Any Adverse Events
Percentage of participants with any adverse events was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.
Time frame: From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Population: Safety analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo® once at least, and were followed up by the physician once or more.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Percentage of Participants With Any Adverse Events | 11.94 Percentage of participants |
Primary
Percentage of Participants With Unexpected Adverse Events
Percentage of participants with unexpected adverse events was reported. The 95% Confidence Interval for the percentage of participants with adverse event was calculated by Exact Method.
Time frame: From baseline (Visit 1) until last visit (the last follow-up visit a patient actually received during the study), up to 349 days.
Population: Safety analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo® once at least, and were followed up by the physician once or more.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Percentage of Participants With Unexpected Adverse Events | 9.03 Percentage of participants |
Secondary
Change in the Body Weight at Last Visit From Baseline
Change in the body weight at Last Visit from baseline was reported.
Time frame: At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness. Only those subjects with non-missing outcome measures were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Change in the Body Weight at Last Visit From Baseline | -2.18 kilogram (kg) | Standard Deviation 3.53 |
p-value: <0.0001Paired t-test
Secondary
Change in the Diastolic Blood Pressure (DBP) at Last Visit From Baseline
Change in the diastolic blood pressure (DBP) at Last Visit from baseline was reported.
Time frame: At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness. Only those subjects with non-missing outcome measures were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Change in the Diastolic Blood Pressure (DBP) at Last Visit From Baseline | -2.04 millimetre of mercury (mmHg) | Standard Deviation 10.8 |
p-value: <0.0001Paired t-test
Secondary
Change in the Fasting Plasma Glucose (FPG) at Last Visit From Baseline
Change in the Fasting Plasma Glucose (FPG) at Last Visit from baseline was reported.
Time frame: At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness. Only those subjects with non-missing outcome measures were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Change in the Fasting Plasma Glucose (FPG) at Last Visit From Baseline | -26.86 milligrams per deciliter (mg/dl) | Standard Deviation 50.91 |
p-value: <0.0001Paired t-test
Secondary
Change in the Glycosylated Hemoglobin (HbA1c) at Last Visit From Baseline
Change in the glycosylated hemoglobin (HbA1c) at Last Visit from baseline was reported.
Time frame: At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Change in the Glycosylated Hemoglobin (HbA1c) at Last Visit From Baseline | -0.72 Percentage of glycosylated hemoglobin | Standard Deviation 1.47 |
p-value: <0.0001Paired t-test
Secondary
Change in the Systolic Blood Pressure (SBP) at Last Visit From Baseline
Change in the systolic blood pressure (SBP) at Last Visit from baseline was reported.
Time frame: At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness. Only those subjects with non-missing outcome measures were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Change in the Systolic Blood Pressure (SBP) at Last Visit From Baseline | -1.96 millimetre of mercury (mmHg) | Standard Deviation 15.45 |
p-value: 0.0076Paired t-test
Secondary
Number of Participants Per Final Effectiveness Assessment Category at Last Visit
Number of participants per final effectiveness assessment category at Last Visit was reported. The final effectiveness consisted of 4 categories: Improved (If determined as there was any effect of maintaining or improving disease related factors.), Unchanged (If disease related factors had not been changed compared with before administration, and not determined as there was any effect of maintaining symptoms.), Aggravated (If disease related factors were worse than before administration.), and Unassessable (If it cannot be determined due to insufficient information collected.).
Time frame: At last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants Per Final Effectiveness Assessment Category at Last Visit | Improved | 330 Participants |
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants Per Final Effectiveness Assessment Category at Last Visit | Unchanged | 103 Participants |
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants Per Final Effectiveness Assessment Category at Last Visit | Aggravated | 45 Participants |
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants Per Final Effectiveness Assessment Category at Last Visit | Unassessable | 19 Participants |
Secondary
Number of Participants Reached Target Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c < 7%) at Last Visit
Number of participants reached target effectiveness response in the glycosylated hemoglobin (HbA1c) (HbA1c \< 7%) at Last Visit was reported. Target effectiveness response in the glycosylated hemoglobin (HbA1c) was defined as HbA1c less than 7%.
Time frame: At last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants Reached Target Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c < 7%) at Last Visit | less than 7% | 239 Participants |
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants Reached Target Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c < 7%) at Last Visit | greater than or equal to 7% | 258 Participants |
Secondary
Number of Participants With Relative Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c Decrease of 0.5% Comparing to Baseline) at Last Visit
Number of participants with relative effectiveness response in the glycosylated hemoglobin (HbA1c) at Last Visit was reported. Relative effectiveness response in the glycosylated hemoglobin (HbA1c) at last visit was defined as HbA1c decrease of 0.5% or more at the last visit comparing to baseline.
Time frame: At baseline (Visit 1) and at last visit (the last follow-up visit a patient actually received during the study, up to Day 349 after baseline).
Population: Effective analysis set: this set included those who signed the informed consent form to participate in this study as subject, took Jardiance Duo®, and were evaluated for the effectiveness.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants With Relative Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c Decrease of 0.5% Comparing to Baseline) at Last Visit | greater than or equal to 0.5% | 242 Participants |
| JARDIANCE DUO® (Empagliflozin/Metformin) | Number of Participants With Relative Effectiveness Response in the Glycosylated Hemoglobin (HbA1c) (HbA1c Decrease of 0.5% Comparing to Baseline) at Last Visit | less than 0.5% | 255 Participants |