Trial Outcomes & Findings for Post-authorization Safety Study in Type 2 Diabetic Patients in Saudi Arabia Treated With Empagliflozin to Assess the Incidence of Ketoacidosis, Severe Complications of Urinary Tract Infection, Volume Depletion, and Dehydration (NCT NCT03764631)
NCT ID: NCT03764631
Last Updated: 2022-02-10
Results Overview
Ketoacidosis is defined as a serious complication of diabetes characterized by high levels of ketones in the body due to lack of insulin and low food intake.
Recruitment status
COMPLETED
Target enrollment
1502 participants
Primary outcome timeframe
Up to 12 months after the index date (defined as the date on which each identified new user received the index prescription for Empagliflozin or DPP-4 inhibitor).
Results posted on
2022-02-10
Participant Flow
A non-interventional study with new data collection from patients with type 2 diabetes mellitus in Saudi Arabia. The study used a "new users" design and compared new users of Empagliflozin to new users of Dipeptidyl peptidase-4 (DPP-4) inhibitors.
Only patients who met all of the inclusion and none of the exclusion criteria were enrolled into the study after signing the informed consent form.
Participant milestones
| Measure |
Empagliflozin
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Overall Study
STARTED
|
751
|
751
|
|
Overall Study
COMPLETED
|
710
|
698
|
|
Overall Study
NOT COMPLETED
|
41
|
53
|
Reasons for withdrawal
| Measure |
Empagliflozin
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Overall Study
Personal Reasons
|
3
|
2
|
|
Overall Study
Switching Therapy
|
3
|
3
|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
33
|
41
|
|
Overall Study
No data as study site was closed
|
2
|
6
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
Total
n=1502 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.1 Years
STANDARD_DEVIATION 10.3 • n=751 Participants
|
52.9 Years
STANDARD_DEVIATION 10.7 • n=751 Participants
|
52.5 Years
STANDARD_DEVIATION 10.5 • n=1502 Participants
|
|
Sex: Female, Male
Female
|
273 Participants
n=751 Participants
|
264 Participants
n=751 Participants
|
537 Participants
n=1502 Participants
|
|
Sex: Female, Male
Male
|
478 Participants
n=751 Participants
|
487 Participants
n=751 Participants
|
965 Participants
n=1502 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: Up to 12 months after the index date (defined as the date on which each identified new user received the index prescription for Empagliflozin or DPP-4 inhibitor).Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed the informed consent.
Ketoacidosis is defined as a serious complication of diabetes characterized by high levels of ketones in the body due to lack of insulin and low food intake.
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Ketoacidosis
|
1 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to 12 months after index date (defined as the date on which each identified new user received the index prescription for Empagliflozin or DPP-4 inhibitor).Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed the informed consent.
Severe UTIs is defined as pyelonephritis or urosepsis.
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Severe Urinary Tract Infections (UTIs)
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 12 months after index date (defined as the date on which each identified new user received the index prescription for Empagliflozin or DPP-4 inhibitor).Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed informed consent.
Volume depletion is defined as the reduction in the extracellular fluids.
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Volume Depletion
|
6 Participants
|
7 Participants
|
PRIMARY outcome
Timeframe: Up to 12 months after index date (defined as the date on which each identified new user received the index prescription for Empagliflozin or DPP-4 inhibitor).Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed informed consent.
Dehydration is defined as the loss of total body water that leads to hypertonicity.
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Dehydration
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day 29.Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed the informed consent.
Ketoacidosis is defined as a serious complication of diabetes characterized by high level of ketones in the body due to lack of insulin and low food intake. Ramadan period is defined as the first day of Ramadan to 29th day of Ramadan based on the Islamic Hijri calendar. The following Ramadan periods were included in this study: * Ramadan month 2019: 5. May to 4. Jun 2019 (± 1 to 2 days) * Ramadan month 2020: 23. April to 23. May 2020 (± 1 to 2 days).
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Ketoacidosis During Ramadan Periods
Ramadan month 2019
|
0 Participants
|
0 Participants
|
|
Number of Participants With Ketoacidosis During Ramadan Periods
Ramadan month 2020
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day 29.Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed the informed consent.
Severe UTIs is defined as pyelonephritis or urosepsis. Ramadan period is defined as the first day of Ramadan to 29th day of Ramadan based on the Islamic Hijri calendar. The following Ramadan periods were included in this study: * Ramadan month 2019: 5. May to 4. Jun 2019 (± 1 to 2 days) * Ramadan month 2020: 23. April to 23. May 2020 (± 1 to 2 days).
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Severe Urinary Tract Infections (UTIs) During Ramadan Periods
Ramadan month 2019
|
0 Participants
|
0 Participants
|
|
Number of Participants With Severe Urinary Tract Infections (UTIs) During Ramadan Periods
Ramadan month 2020
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day 29.Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed the informed consent.
Volume depletion is defined as the reduction in the extracellular fluids. Ramadan period is defined as the first day of Ramadan to 29th day of Ramadan based on the Islamic Hijri calendar. The following Ramadan periods were included in this study: * Ramadan month 2019: 5. May to 4. Jun 2019 (± 1 to 2 days) * Ramadan month 2020: 23. April to 23. May 2020 (± 1 to 2 days).
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Volume Depletion During Ramadan Periods
Ramadan month 2019
|
0 Participants
|
0 Participants
|
|
Number of Participants With Volume Depletion During Ramadan Periods
Ramadan month 2020
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day 29.Population: Enrolled Set: All patients with type 2 diabetes mellitus included in the study who signed the informed consent.
Dehydration is defined as the loss of total body water that leads to hypertonicity. Ramadan period is defined as the first day of Ramadan to 29th day of Ramadan based on the Islamic Hijri calendar. The following Ramadan periods were included in this study: * Ramadan month 2019: 5. May to 4. Jun 2019 (± 1 to 2 days) * Ramadan month 2020: 23. April to 23. May 2020 (± 1 to 2 days).
Outcome measures
| Measure |
Empagliflozin
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 Participants
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Number of Participants With Dehydration During Ramadan Periods
Ramadan month 2019
|
0 Participants
|
0 Participants
|
|
Number of Participants With Dehydration During Ramadan Periods
Ramadan month 2020
|
0 Participants
|
0 Participants
|
Adverse Events
Empagliflozin
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
DPP-4 Inhibitors
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Empagliflozin
n=751 participants at risk
Patients with type 2 diabetes mellitus (T2DM) and newly using Empagliflozin (e.g. Patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or Dipeptidyl peptidase-4 (DPP-4) inhibitors during the previous 12 months). Empagliflozin was administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
DPP-4 Inhibitors
n=751 participants at risk
Patients with type 2 diabetes mellitus (T2DM) and newly using Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. patients had not used other Sodium/Glucose co-transporter 2 (SLGT2) or DPP-4 inhibitors during the previous 12 months). DPP-4 inhibitors were administered according to the approved labels in Saudi Arabia. Patients were followed up for 12 months after the index date.
|
|---|---|---|
|
Cardiac disorders
Myocardial ischaemia
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
Gastrointestinal disorders
Anal fissure
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
General disorders
Hernia
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
Infections and infestations
Pneumonia
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
Metabolism and nutrition disorders
Obesity
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
|
Renal and urinary disorders
End stage renal disease
|
0.00%
0/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
0.13%
1/751 • Up to 12 months.
Enrolled Set: All patients with type 2 diabetes mellitus included in this study who signed the informed consent.
|
Other adverse events
Adverse event data not reported
Additional Information
Boehringer Ingelheim, Call Centre
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER