Characteristics of Empagliflozin Initiators

• ClinicalTrials.gov Identifier: NCT03050619
• Recruitment Status: Completed
• First Posted: February 13, 2017
• Results First Posted: January 25, 2019
• Last Update Posted: January 25, 2019
• Sponsor: Boehringer Ingelheim
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

Empagliflozin, a sodium glucose cotransporter 2 (SGLT-2) inhibitor, was launched in the United Kingdom (UK) in August 2014. It can be expected that patients initiating empagliflozin may differ in their characteristics from patients initiating other glucose lowering drugs (GLDs) that have been on the market longer (e.g. patients may have poorer glucose control). Therefore, the proposed study aims to characterize patients with T2DM in the UK initiating empagliflozin in terms of baseline characteristics, concomitant medications, and comorbidities compared to patients with type 2 diabetes mellitus (T2DM) initiating other SGLT-2 inhibitors or other non-insulin GLDs. Due to the mode of action, some patients taking empagliflozin have experienced weight loss in clinical trials. A theoretical possibility exists that empagliflozin may be used by patients without T2DM. Therefore, this study also aims to assess the potential off-label use of empagliflozin compared to other non-insulin GLDs.

Condition or disease	Intervention/treatment
Type 2 Diabetes	Drug: Empagliflozin; Drug: Other SGLT2 inhibitors; Drug: Other non-insulin GLDs

Detailed Description:

Study Design:

cross sectional

Study Design

• Study Type: Observational
• Actual Enrollment: 31908 participants
• Observational Model: Other
• Time Perspective: Retrospective
• Official Title: Characteristics of Patients Initiating Empagliflozin or Other Non-insulin Glucose Lowering Drugs in the United Kingdom
• Actual Study Start Date: September 10, 2016
• Actual Primary Completion Date: October 14, 2016
• Actual Study Completion Date: October 14, 2016

Groups and Cohorts

Group/Cohort	Intervention/treatment
New users of Empagliflozin; New users of empagliflozin	Drug: Empagliflozin
New users of Other SGLT2 inhibitors; New users of other SGLT2 inhibitors	Drug: Other SGLT2 inhibitors
New users of Other non-insulin GLDs; New users of other non-insulin GLDs	Drug: Other non-insulin GLDs; metformin, sulfonylureas, DPP-4 inhibitors, GLP-1 agonists

Outcome Measures

Primary Outcome Measures :

1. Baseline Characteristics of Adults (as Measured by Demographics) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by demographics) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) are presented.
2. Baseline Characteristics of Adults (as Measured by Life Style Factors (Smoking and Alcohol Use)) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by life style factors (smoking and alcohol use)) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) are presented. NA= NR (Not Reported) (variables for which patient counts were <5)
3. Baseline Characteristics of Adults (as Measured by Life Style Factors (BMI)) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by life style factors (BMI)) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) is presented. Mean and standard deviation (SD) of body mass index (BMI) measured is presented along with number of subjects with available data.
4. Baseline Characteristics of Adults (as Measured by Life Style Factors (Blood Pressure)) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by life style factors (blood pressure)) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) is presented. Mean and standard deviation (SD) of Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) measured is presented along with number of subjects with available data.
5. Baseline Characteristics of Adults (as Measured by Glycated Haemoglobin (HbA1c)) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by glycated haemoglobin (HbA1c)) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) is presented. Mean and standard deviation (SD) of glycated haemoglobin (HbA1c) measured is presented along with number of subjects with available data.
6. Baseline Characteristics of Adults (as Measured by Laboratory Tests) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by laboratory tests) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) are presented. Mean and standard deviation (SD) of total cholesterol (TC), high-density lipoproteins level (HDL), Low-density lipoprotein level (LDL) and triglyceride level (TG) measured are presented along with number of subjects with available data.
7. Baseline Characteristics of Adults (as Measured by Estimated Glomerular Filtration Rate (eGFR)) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by estimated glomerular filtration rate (eGFR)) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) is presented. Mean and standard deviation (SD) of estimated glomerular filtration rate (eGFR) measured is presented along with number of subjects with available data.
8. Baseline Characteristics of Adults (as Measured by Creatinine Serum (SCR)) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by by creatinine serum (SCR)) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) is presented. Mean and standard deviation (SD) of creatinine serum (SCR) measured is presented along with number of subjects with available data.
9. Baseline Characteristics of Adults (as Measured by Comorbidities) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
   Baseline characteristics of adults (as measured by comorbidities) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) are presented.
10. Baseline Characteristics of Adults (as Measured by Concomitant Medications) With a Recorded Diagnosis of T2DM Starting Index Prescriptions in the UK [ Time Frame: Baseline ]
    Baseline characteristics of adults (as measured by concomitant medications) with a recorded diagnosis of T2DM who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) are presented. Subjects taking medication up to 60 days before index date are presented.

Secondary Outcome Measures :

1. Extent of Off-label Use [ Time Frame: Baseline ]
   To assess off-label use the number of study participants without a recorded diagnosis of T2DM was calculated for each exposure category (people with other types of diabetes, people without diabetes, people younger than 18 years old, and women during pregnancy and breastfeeding). For the assessment of drug use during the pregnancy and breastfeeding period, the look-back period was 270 days (9 months) before and including the index date. To assess the use in pediatric population, the study participants were stratified by age into adults (≥18 years of age) and pediatrics (<18 years of age).
2. Baseline Characteristics (as Measured by Demographics) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by demographics) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label are presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
3. Baseline Characteristics (as Measured by Life Style Factors (Smoking and Alcohol Use)) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by life style factors (smoking and alcohol use)) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label are presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category. NA= NR (Not Reported) (variables for which patient counts were <5)
4. Baseline Characteristics (as Measured by Life Style Factors (BMI)) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by life style factors (BMI)) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label is presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
5. Baseline Characteristics (as Measured by Life Style Factors (Blood Pressure)) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by life style factors (blood pressure)) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label is presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
6. Baseline Characteristics (as Measured b Yglycated Haemoglobin (HbA1c)) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by glycated haemoglobin (HbA1c)) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label is presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
7. Baseline Characteristics (as Measured by Laboratory Tests) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by laboratory tests) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label are presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
8. Baseline Characteristics (as Measured by Estimated Glomerular Filtration Rate (eGFR)) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by estimated glomerular filtration rate (eGFR)) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label is presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
9. Baseline Characteristics (as Measured by Creatinine Serum (SCR)) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
   Baseline characteristics of patients (as measured by creatinine serum (SCR)) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label is presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
10. Baseline Characteristics (as Measured by Comorbidities) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
    Baseline characteristics of patients (as measured by comorbidities) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label are presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category.
11. Baseline Characteristics (as Measured by Concomitant Medications) of Patients Starting Index Prescriptions Off-label [ Time Frame: Baseline ]
    Baseline characteristics of patients (as measured by concomitant medications) who initiated index prescriptions (empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs (comprising DPP-4i, metformin, SU and GLP-1 agonists)) off-label are presented. Use of empagliflozin, other SGLT-2i or other commonly used non-insulin GLDs in other types of diabetes (other than T2DM) or without diabetes or in people younger than 18 years old or in women during pregnancy or during breastfeeding is considered as off-label. As per CPRD guideline, no cell that contains <5 events should be reported to protect patient confidentiality. Since empagliflozin group reported <5 events for all off-label categories except for unspecified DM therefore baseline characteristics are presented for only unspecified DM category. Subjects taking medication up to 60 days before index date are presented.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

New users of empagliflozin and other non-insulin GLDs in the UK CPRD between 1 Aug 2014 to 1 Sep 2015

Criteria

Inclusion criteria:

All patients will be required to meet all of the following criteria:

• At least 12 months of continuous registration prior to the index date in a practice contributing up to standard (UTS) data to the Clinical Practice Research Datalink (CPRD). Infants younger than 1 year will not be required to have 12 months of continuous UTS registration in the CPRD.
• A new user of one of the index prescriptions (empagliflozin, other SGLT2 inhibitor, or non-insulin GLDs) or a fixed dose combination (FDC) with metformin.

Exclusion criteria:

There is no exclusion criterion in this study.

Contacts and Locations

Locations

Germany

Boehringer Ingelheim Investigational Site

Ingelheim, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Eli Lilly and Company

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Synopsis Link 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03050619
• Other Study ID Numbers: 1245.122
• First Posted: February 13, 2017
• Results First Posted: January 25, 2019
• Last Update Posted: January 25, 2019
• Last Verified: August 2018

Additional relevant MeSH terms:

Empagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs