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

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

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Empagliflozin; Drug: Dipeptidyl-peptidase 4 (DPP-4) inhibitors

• Study Type: Observational
• Enrollment (Actual): 1502

Contacts and Locations

Study Locations

• Saudi Arabia
  • Abha, Saudi Arabia, 61431
    • Abha International Private Hospital
  • Jeddah, Saudi Arabia, 21214
    • DAFA Special Polyclinic
  • Jeddah, Saudi Arabia, 21412
    • Ghassan Najeeb Pharaon Hospital
  • Jeddah, Saudi Arabia, 21451
    • International Medical Center
  • Jeddah, Saudi Arabia, 21452
    • Dr.Bakhsh Hospital
  • Jeddah, Saudi Arabia, 21461
    • Dr. Soliman Fakeeh Hospital
  • Jeddah, Saudi Arabia, 21461
    • Saudi German Hospital
  • Jeddah, Saudi Arabia, 21573
    • Al Abeer Medical Center
  • Jeddah, Saudi Arabia, 21573
    • Al-Abeer Medical Center
  • Jeddah, Saudi Arabia, 23531
    • Al Abeer Polyclinic
  • Makkah, Saudi Arabia, 24232
    • Al Rahman Polyclinic
  • Makkah, Saudi Arabia, 24232
    • Shifa Hospital
  • Makkah, Saudi Arabia, 24241
    • Al-Noor Specialist Hospital
  • Najran, Saudi Arabia, 66261
    • Al Zafer Hospital
  • Riyadh, Saudi Arabia, 11525
    • Obesity, Endocrine and Metabolism Center
  • Riyadh, Saudi Arabia, 11533
    • Riyadh Medical Center
  • Riyadh, Saudi Arabia, 13214
    • Alalam Medical Center
  • Tabuk, Saudi Arabia, 47311
    • Prince Fahad bin Sultan hospital
  • Taif, Saudi Arabia, 21944
    • Al Hada Armed Forces Hospital
  • Yanbu, Saudi Arabia, 46455
    • Al Amal Medical Group
  • Yanbu, Saudi Arabia, 46455
    • Alansari Specialist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Main diagnosis for study entry

-Patients diagnosed with T2DM will be included.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
subjects with Type 2 Diabetes mellitus	Drug: Empagliflozin; Drug; Drug: Dipeptidyl-peptidase 4 (DPP-4) inhibitors; Dipeptidyl-peptidase 4 - Drug

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Ahmed Mansour, +201028866717, ahmed.mansour@boehringer-ingelheim.com

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 26, 2018
• Primary Completion (ACTUAL): January 11, 2021
• Study Completion (ACTUAL): January 11, 2021

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (ACTUAL): December 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Infections; Urologic Diseases; Endocrine System Diseases; Water-Electrolyte Imbalance; Acid-Base Imbalance; Acidosis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Urinary Tract Infections; Dehydration; Hypovolemia; Ketosis; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: 1245-0149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. Studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. Studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:

1. find information in order to request access to clinical study data, for listed studies.
2. request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No