Real World Glycemic Effectiveness of Linagliptin

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03338803
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 11,001
• Location: 1
• Actual Duration (Months): 2.4
• Patients Per Site Per Month: 4586.9

Study Details

Study Description

Brief Summary

A non-interventional cohort study using existing data from patients in the Optum Clinical Database which contains electronic health record (EHR) data from providers across the United States to determine whether there is comparable effectiveness of linagliptin on glycemic effectiveness

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Linagliptin

Study Design

• Study Type: Observational
• Actual Enrollment: 11001 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Real World Glycemic Effectiveness of Linagliptin Among Type 2 Diabetes Mellitus Adults by Age and Renal Function
• Actual Study Start Date: Nov 21, 2017
• Actual Primary Completion Date: Feb 2, 2018
• Actual Study Completion Date: Feb 2, 2018

Arms and Interventions

Arm	Intervention/Treatment
Patients with a written prescription for linagliptin	Drug: Linagliptin; drug; Other Names: ONDERO, TRAJENTA, TRAYENTA, TRAZENTA, TRADJENTA

Outcome Measures

Primary Outcome Measures

1. Change in Glycosylated Hemoglobin (HbA1c) Across Age Categories [Baseline and 60 to 180 days]

   Change in HbA1c among adults with type 2 diabetes mellitus (T2DM) within the 60 to 180 days following initiation of linagliptin across pre-defined age categories (40 to 54 years, 40 to 54 years, 65 to 74 years and 75+ years). Change in HbA1c, was calculated for each patient by subtracting the patient's last (most recent) HbA1c value during the pre-index period (including the index date) from the patient's last (most recent) HbA1c value 60 to 180 days after the index date.

2. Change in Glycosylated Hemoglobin (HbA1c) Across Renal Function Categories [Baseline and 60 to 180 days]

   Change in HbA1c among adults with type 2 diabetes mellitus (T2DM) within the 60 to 180 days following initiation of linagliptin across pre-defined renal function categories. Change in HbA1c, was calculated for each patient by subtracting the patient's last (most recent) HbA1c value during the pre-index period (including the index date) from the patient's last (most recent) HbA1c value 60 to 180 days after the index date. Renal function categories were presented based on patients with a pre-index estimated glomerular filtration rate (eGFR) value (eGFR<30, eGFR 30 to 44, eGFR 45 to 59, eGFR 60 to 89, eGFR ≥ 90 milliliter/ minute/1.73 meter^2 and eGFR not available).

Secondary Outcome Measures

1. Percentage of Adults With T2DM Who Achieve HbA1c < 7.0% Across the Pre-defined Age Categories [60 to 180 days]

   Percentage of adults with T2DM who achieve HbA1c < 7.0% within the 60 to 180 days following initiation of linagliptin across pre-defined age categories (40 to 54 years, 40 to 54 years, 65 to 74 years and 75+ years).

2. Percentage of Adults With T2DM Who Achieve HbA1c < 7.0% Across Renal Function Categories [60 to 180 days]

   Percentage of adults with T2DM who achieve HbA1c < 7.0% within the 60 to 180 days following initiation of linagliptin across pre-defined renal function categories. Renal function categories were presented based on patients with a pre-index estimated glomerular filtration rate (eGFR) value (eGFR<30, eGFR 30 to 44, eGFR 45 to 59, eGFR 60 to 89, eGFR ≥ 90 milliliter/ minute /1.73 meter^2 and eGFR not available).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ≥ 1 written prescription for linagliptin (Tradjenta®, Jentadueto®, or Jentadueto XR®)in the EHR (electronic health record) data during the identification period

• ≥ 40 years of age based on the year of the index date

• First active date in the EHR is ≥ 180 days prior to the index date

• ≥ 1 diagnosis code representing Type 2 diabetes (T2DM) in the EHR data during the 180-day pre-index period or on the index date

• ≥ 1 HbA1c value during the 180-day pre-index period or on the index date

• ≥ 1 HbA1c value 60 to 180 days after the index date

Exclusion Criteria:

• ≥ 1 written prescription, medication administration or medication history record for linagliptin or other dipeptidyl peptidase (DPP-4) inhibitor in the EHR data during the 180-day pre-index period

• ≥ 1 written prescription or medication administration for a new antihyperglycemic medication other than linagliptin on the index date New antihyperglycemic medication will be defined as a written prescription or medication administration for any antihyperglycemic medication that was not present in the patient's written prescription, medication administration, or medication history records during the 180-day pre-index period.

Individual antihyperglycemic medications will be distinguished by generic name using the column labelled "Medication Name" in Tables 2 through 13. Combination products containing two generic ingredients will be considered as two distinct antihyperglycemic medications Note: This exclusion criterion is designed to exclude patients from the study sample if they start a new antihyperglycemic medication other than linagliptin on the index date. Patients that start a new antihyperglycemic medication in the follow-up period will not be removed from the study sample to avoid creating a biased sample. Addition of a new antihyperglycemic medication during follow-up will be evaluated through the sensitivity analysis described in Section 9.7.4.4. While we will be capturing additions of new therapies, discontinuation of linagliptin is not able to be accurately measured in electronic record data. The electronic record data capture prescriptions written by a prescriber, but it is not possible to know if patients received and adhered to their medication and there are no structured data fields to identify if and when a medication was discontinued by the patient or the provider

• ≥ 1 diagnosis code or procedure code representing renal transplant, solid organ transplant, or bone marrow transplant in the EHR data during the 180-day pre-index period or on the index date

• ≥ 1 diagnosis code representing malignancy in the EHR data during the 180-day preindex period or on the index date

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Optum	Eden Prairie	Minnesota	United States	55344

Sponsors and Collaborators

• Boehringer Ingelheim
• Eli Lilly and Company

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 20, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03338803
• Other Study ID Numbers: 1218-0182
• First Posted: Nov 9, 2017
• Last Update Posted: May 6, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Linagliptin

Study Results

Participant Flow

Recruitment Details	Non-interventional, retrospective cohort study using existing data from patients in the Optum Clinical Database which contains electronic health record (EHR) data for the period of 01 July 2011 through 31 March 2017.
Pre-assignment Detail	Type 2 diabetes mellitus (T2DM) patients with written prescription for initiating Linagliptin (Tradjenta®, Jentadueto®, or Jentadueto XR®) were identified during identification period starting on 01 January 2012 and ending on 30 September 2016. Aim was to describe real world glycemic-lowering effectiveness across range of ages and renal function.

Arm/Group Title	Patients With Written Prescription for Initiating Linagliptin
Arm/Group Description	Patients with a first written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.
Period Title: Overall Study
STARTED	11001
COMPLETED	11001
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Patients With Written Prescription for Initiating Linagliptin
Arm/Group Description	Patients with a first written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.
Overall Participants	11001
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.30 (11.37)
Sex: Female, Male (Count of Participants)
Female	5603 50.9%
Male	5398 49.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	927 8.4%
Not Hispanic or Latino	9550 86.8%
Unknown or Not Reported	524 4.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	241 2.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1455 13.2%
White	8645 78.6%
More than one race	0 0%
Unknown or Not Reported	660 6%
Estimated glomerular filtration rate (eGFR) (participants) [Number]
<30	679 6.2%
30 to 44	1646 15%
45 to 59	1727 15.7%
60 to 89	3256 29.6%
≥ 90	2603 23.7%
eGFR not available	1090 9.9%
Age categories (participants) [Number]
40 to 54 years	2325 21.1%
55 to 64 years	3332 30.3%
65 to 74 years	3077 28%
75 years and above	2267 20.6%

Outcome Measures

1. Primary Outcome

Title	Change in Glycosylated Hemoglobin (HbA1c) Across Age Categories
Description	Change in HbA1c among adults with type 2 diabetes mellitus (T2DM) within the 60 to 180 days following initiation of linagliptin across pre-defined age categories (40 to 54 years, 40 to 54 years, 65 to 74 years and 75+ years). Change in HbA1c, was calculated for each patient by subtracting the patient's last (most recent) HbA1c value during the pre-index period (including the index date) from the patient's last (most recent) HbA1c value 60 to 180 days after the index date.
Time Frame	Baseline and 60 to 180 days

Outcome Measure Data

Analysis Population Description

Patients with a written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.

Arm/Group Title	Patients With Written Prescription for Initiating Linagliptin
Arm/Group Description	Patients with a first written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.
Measure Participants	11001
Overall	-0.51 (1.46)
Age 40 to 54 years	-0.65 (1.65)
Age 55 to 64 years	-0.59 (1.54)
Age 65 to 74 years	-0.43 (1.36)
Age 75+ years	-0.36 (1.21)

2. Primary Outcome

Title	Change in Glycosylated Hemoglobin (HbA1c) Across Renal Function Categories
Description	Change in HbA1c among adults with type 2 diabetes mellitus (T2DM) within the 60 to 180 days following initiation of linagliptin across pre-defined renal function categories. Change in HbA1c, was calculated for each patient by subtracting the patient's last (most recent) HbA1c value during the pre-index period (including the index date) from the patient's last (most recent) HbA1c value 60 to 180 days after the index date. Renal function categories were presented based on patients with a pre-index estimated glomerular filtration rate (eGFR) value (eGFR<30, eGFR 30 to 44, eGFR 45 to 59, eGFR 60 to 89, eGFR ≥ 90 milliliter/ minute/1.73 meter^2 and eGFR not available).
Time Frame	Baseline and 60 to 180 days

Outcome Measure Data

Analysis Population Description

Patients with a written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.

Arm/Group Title	Patients With Written Prescription for Initiating Linagliptin
Arm/Group Description	Patients with a first written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.
Measure Participants	11001
Overall	-0.51 (1.46)
eGFR<30	-0.22 (1.46)
eGFR 30 to 44	-0.33 (1.34)
eGFR 45 to 59	-0.47 (1.42)
eGFR 60 to 89	-0.55 (1.44)
eGFR ≥ 90	-0.70 (1.58)
eGFR not available	-0.45 (1.40)

3. Secondary Outcome

Title	Percentage of Adults With T2DM Who Achieve HbA1c < 7.0% Across the Pre-defined Age Categories
Description	Percentage of adults with T2DM who achieve HbA1c < 7.0% within the 60 to 180 days following initiation of linagliptin across pre-defined age categories (40 to 54 years, 40 to 54 years, 65 to 74 years and 75+ years).
Time Frame	60 to 180 days

Outcome Measure Data

Analysis Population Description

Patients with a written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.

Arm/Group Title	Patients With Written Prescription for Initiating Linagliptin
Arm/Group Description	Patients with a first written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.
Measure Participants	11001
Overall	35.72
Age 40 to 54 years	30.28
Age 55 to 64 years	35.59
Age 65 to 74 years	37.89
Age 75+ years	38.55

4. Secondary Outcome

Title	Percentage of Adults With T2DM Who Achieve HbA1c < 7.0% Across Renal Function Categories
Description	Percentage of adults with T2DM who achieve HbA1c < 7.0% within the 60 to 180 days following initiation of linagliptin across pre-defined renal function categories. Renal function categories were presented based on patients with a pre-index estimated glomerular filtration rate (eGFR) value (eGFR<30, eGFR 30 to 44, eGFR 45 to 59, eGFR 60 to 89, eGFR ≥ 90 milliliter/ minute /1.73 meter^2 and eGFR not available).
Time Frame	60 to 180 days

Outcome Measure Data

Analysis Population Description

Patients with a written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.

Arm/Group Title	Patients With Written Prescription for Initiating Linagliptin
Arm/Group Description	Patients with a first written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.
Measure Participants	11001
Overall	35.72
eGFR<30	46.69
eGFR 30 to 44	38.88
eGFR 45 to 59	40.19
eGFR 60 to 89	35.75
eGFR ≥ 90	30.12
eGFR not available	30.37

Adverse Events

Time Frame	Individual safety reporting is not applicable for this study
Adverse Event Reporting Description	This is a retrospective observational study using secondary data, in which all patient data will be collected and analyzed in aggregate. Individual patient safety related information will not be captured during this study. Thus, individual safety reporting is not applicable for this study.
Arm/Group Title	Patients With Written Prescription for Initiating Linagliptin
Arm/Group Description	Patients with a first written prescription for linagliptin were identified during an identification period starting on 01 January 2012 and ending on 30 September 2016.
All Cause Mortality
	Patients With Written Prescription for Initiating Linagliptin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Patients With Written Prescription for Initiating Linagliptin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Patients With Written Prescription for Initiating Linagliptin
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.