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

Study Overview
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Brief Summary
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The objectives of this study are to assess the risk of ketoacidosis, severe urinary tract infections, volume depletion, and dehydration associated in patients with T2DM initiating Empagliflozin compared to patient initiating a dipeptidyl peptidase-4 (DPP-4) inhibitors over a 12-month period of follow-up, including the month of Ramadan

Official Title
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Post-authorization Safety Study in Patients With Type 2 Diabetes Mellitus to Assess the Incidence of Ketoacidosis, Severe Complications of Urinary Tract Infection, Volume Depletion, and Dehydration Among Patients Treated With Empagliflozin or DPP-4 Inhibitors in Saudi Arabia

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Dipeptidyl-peptidase 4 (DPP-4) inhibitors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have signed Informed consent form. The patients will be at least 18 years old at index date, diagnosed with Type 2 diabetes mellitus (T2DM) in Saudi Arabia, and who will initiate Empagliflozin or Dipeptidyl-peptidase 4 (DPP4) inhibitors treatment according to the local label and at the discretion of the treating physician during the study period, who have not used other sodium/glucose co-transporter 2 (SGLT2) or DPP4 inhibitors during the previous 12 months. Exclusion Criteria: Known hypersensitivity to Empagliflozin, the comparator DPP-4 inhibitors or any of their excipients Patients for whom Empagliflozin or the comparator DPP-4 inhibitor is contraindicated according Saudi Food and Drug Authority (SFDA) approved label Patients prescribed fixed-dose combinations of SGLT2 inhibitors with DPP-4 inhibitors will be excluded. The same inclusion and exclusion criteria will be applied to the comparator group, which will include new users of DPP-4 inhibitors.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| subjects with Type 2 Diabetes mellitus<br> | Drug: Empagliflozin<br>* Drug<br>Drug: Dipeptidyl-peptidase 4 (DPP-4) inhibitors<br>* Dipeptidyl-peptidase 4 - Drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Ketoacidosis | 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. | 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). | 
| Number of Participants With Severe Urinary Tract Infections (UTIs) | Severe UTIs is defined as pyelonephritis or urosepsis. | 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). | 
| Number of Participants With Volume Depletion | Volume depletion is defined as the reduction in the extracellular fluids. | 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). | 
| Number of Participants With Dehydration | Dehydration is defined as the loss of total body water that leads to hypertonicity. | 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). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Ketoacidosis During Ramadan Periods | 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). | Up to day 29. | 
| Number of Participants With Severe Urinary Tract Infections (UTIs) During Ramadan Periods | 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). | Up to day 29. | 
| Number of Participants With Volume Depletion During Ramadan Periods | 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). | Up to day 29. | 
| Number of Participants With Dehydration During Ramadan Periods | 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). | Up to day 29. |