ADA Linagliptin in Long Term Care

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02061969
• Collaborator: American Diabetes Association (Other)
• Enrollment: 140
• Locations: 4
• Arms: 2
• Duration (Months): 35.5
• Patients Per Site: 35
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This is a study to determine whether glycemic control, as measured by change in HbA1c and frequency of hypoglycemia, is different between treatment with linagliptin (Tradjenta®) and basal insulin in long term care residents(LTC) with Type 2 diabetes(T2D). Patients with poorly controlled diabetes (HbA1c >7.5%) will be randomized to a 6-month intervention with linagliptin or glargine insulin (± metformin for both treatments). Our hypothesis is that treatment with linagliptin, a once daily DPP4-inhibitor, will result in similar improvement in glucose control but in a lower rate of hypoglycemia than insulin treatment in LTC residents with T2D. We will also determine differences in clinical outcome, resource utilization, and hospitalization costs between LTC residents with T2D treated with linagliptin and basal and correction insulin. We will compare differences in complications (infectious and non-infectious, neurological and cardiovascular events), emergency room visits and hospitalizations between groups during the 6 months of intervention.

Condition or Disease	Intervention/Treatment	Phase
Diabetes	Drug: linagliptin; Drug: insulin glargine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Study Comparing a DPP4 Inhibitor (Linagliptin) and Basal Insulin (Glargine) in Long-Term Care Residents With Type 2 Diabetes
• Study Start Date: Apr 25, 2014
• Actual Primary Completion Date: Apr 10, 2017
• Actual Study Completion Date: Apr 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Insulin glargine Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period.	Drug: insulin glargine; Other Names: Lantus
Experimental: linagliptin Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period.	Drug: linagliptin; 5mg linagliptin tablets; Other Names: Tradjenta

Outcome Measures

Primary Outcome Measures

1. Mean Fasting Blood Glucose Level [6 months]

   The primary endpoint of the study is differences between treatment groups in mean fasting blood glucose level in LTC residents with poorly controlled diabetes.

Secondary Outcome Measures

1. HbA1c [6 months]

   HbA1c at 6 month

2. Number of Hypoglycemic Events < 70mg/dl [over 6 months]

   total number of hypoglycemic events (<70 mg/dl)

3. Number of Hypoglycemic Events < 40mg/dl [over 6 months]

   total number of severe hypoglycemia (< 40 mg/dl).

4. Total Daily Dose of Insulin [over 6 months]

   Total daily dose of insulin (units)

5. Changes in Cognitive Function [over 6 months]

   Data on changes in cognitive function were not collected

6. Number of Participants With Acute Complications [over 6 months]

   Number of Participants with Acute Complications (urinary tract infections, pneumonia, bedsores, diabetic foot infection).

7. Total Number of Emergency Room Visits [6 months]

   Total number of emergency room visits during the study period

8. Total Number of Hospital Visits [6 months]

   Total number of hospital visits during the study period

9. Total Number of Complications [6 months]

   Total number of complications including urinary tract infections, pneumonia, diabetic foot infection, cardiac complications including myocardial infarction and heart failure, cerebrovascular accidents, and acute kidney injury and mortality.

10. Incidence of Acute Kidney Injury [over 6 months]

    Acute kidney injury in LTC Residents Treated with Basal Insulin and Linagliptin Therapy

11. Mortality [over 6 months]

    Mortality is defined as death occurring during admission at the LTC facility

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males or females with known history of type 2 diabetes, treated with diet, OADs as monotherapy or in combination therapy (excluding DPP4 inhibitors), or sliding scale insulin.

2. Subjects with HbA1c > 7.5% and/or any blood glucose greater than or equal to 180 mg/dL

Exclusion Criteria:

1. Subjects with a history of type 1 diabetes or with a history of diabetic ketoacidosis

2. Treatment with insulin or GLP1 analogs during the past 3 months prior to admission.

3. Recurrent severe hypoglycemia or hypoglycemic unawareness.

4. Subjects with history of gastrointestinal obstruction or gastroparesis.

5. Patients with acute or chronic pancreatitis or pancreatic cancer.

6. Patients with clinically significant hepatic disease (cirrhosis, jaundice, end-stage liver disease, portal hypertension) and elevated ALT and AST > 3 times upper limit of normal, or significantly impaired renal function (GFR < 45 ml/min).

7. Treatment with corticosteroids, parenteral nutrition and immunosuppressive treatment.

8. Mental condition rendering the subject unable to understand the nature and scope of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Crestvew Nursing Home	Atlanta	Georgia	United States	30315
2	Budd Terrace Nursing Home	Atlanta	Georgia	United States	30322
3	Wesley Woods Nursing Home	Atlanta	Georgia	United States	30322
4	VA Nursing Home	Decatur	Georgia	United States	30033

Sponsors and Collaborators

• Emory University
• American Diabetes Association

Investigators

• Principal Investigator: Guillermo Umpierrez, MD, Emory University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 11, 2017

More Information

Publications

None provided.

• Responsible Party: Guillermo Umpierrez, MD, Professor of Medicine, Emory University
• ClinicalTrials.gov Identifier: NCT02061969
• Other Study ID Numbers: IRB00071545; IRB00071946
• First Posted: Feb 13, 2014
• Last Update Posted: Aug 22, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Guillermo Umpierrez, MD, Professor of Medicine, Emory University: nursing home facility; long-term care facility; older patients; elderly patients; hyperglycemia; type 2 diabetes
• Additional relevant MeSH terms: Diabetes Mellitus; Insulin Glargine; Linagliptin

Study Results

Participant Flow

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Period Title: Overall Study
STARTED	73	67
COMPLETED	73	67
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Insulin Glargine	Linagliptin	Total
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine.	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets.	Total of all reporting groups
Overall Participants	73	67	140
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.5 (13)	68 (14)	69.8 (13)
Sex: Female, Male (Count of Participants)
Female	48 65.8%	35 52.2%	83 59.3%
Male	25 34.2%	32 47.8%	57 40.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	42 57.5%	42 62.7%	84 60%
White	30 41.1%	22 32.8%	52 37.1%
More than one race	1 1.4%	3 4.5%	4 2.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	73 100%	67 100%	140 100%

Outcome Measures

1. Primary Outcome

Title	Mean Fasting Blood Glucose Level
Description	The primary endpoint of the study is differences between treatment groups in mean fasting blood glucose level in LTC residents with poorly controlled diabetes.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Mean (Standard Deviation) [mg/dl]	136.4 (35)	131.2 (27)

2. Secondary Outcome

Title	HbA1c
Description	HbA1c at 6 month
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Mean (Standard Deviation) [percent of glycosylated hemoglobin]	6.58 (0.7)	6.82 (0.6)

3. Secondary Outcome

Title	Number of Hypoglycemic Events < 70mg/dl
Description	total number of hypoglycemic events (<70 mg/dl)
Time Frame	over 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Number [events]	136	3

4. Secondary Outcome

Title	Number of Hypoglycemic Events < 40mg/dl
Description	total number of severe hypoglycemia (< 40 mg/dl).
Time Frame	over 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Number [events]	3	0

5. Secondary Outcome

Title	Total Daily Dose of Insulin
Description	Total daily dose of insulin (units)
Time Frame	over 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Mean (Standard Deviation) [U/day]	12.0 (9.9)	4.03 (1.7)

6. Secondary Outcome

Title	Changes in Cognitive Function
Description	Data on changes in cognitive function were not collected
Time Frame	over 6 months

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	0	0

7. Secondary Outcome

Title	Number of Participants With Acute Complications
Description	Number of Participants with Acute Complications (urinary tract infections, pneumonia, bedsores, diabetic foot infection).
Time Frame	over 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Count of Participants [Participants]	8 11%	5 7.5%

8. Secondary Outcome

Title	Total Number of Emergency Room Visits
Description	Total number of emergency room visits during the study period
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Number [visits]	3	0

9. Secondary Outcome

Title	Total Number of Hospital Visits
Description	Total number of hospital visits during the study period
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Number [visits]	6	7

10. Secondary Outcome

Title	Total Number of Complications
Description	Total number of complications including urinary tract infections, pneumonia, diabetic foot infection, cardiac complications including myocardial infarction and heart failure, cerebrovascular accidents, and acute kidney injury and mortality.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Number [events]	22	16

11. Secondary Outcome

Title	Incidence of Acute Kidney Injury
Description	Acute kidney injury in LTC Residents Treated with Basal Insulin and Linagliptin Therapy
Time Frame	over 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Number [events]	2	1

12. Secondary Outcome

Title	Mortality
Description	Mortality is defined as death occurring during admission at the LTC facility
Time Frame	over 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Insulin Glargine	Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine	Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
Measure Participants	73	67
Count of Participants [Participants]	0 0%	2 3%

Adverse Events

Time Frame	6 months
Arm/Group Title	Insulin Glargine		Linagliptin
Arm/Group Description	Insulin glargine starting at 0.1 unit/kg/day added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. Insulin glargine		Oral linagliptin 5mg once daily added to ongoing metformin if the patient is already on it. The duration will be for a 6-month period. linagliptin: 5mg linagliptin tablets
All Cause Mortality
	Insulin Glargine		Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		2/67 (3%)
Serious Adverse Events
	Insulin Glargine		Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/73 (8.2%)		4/67 (6%)
Cardiac disorders
Hospitalization for congestive heart failure ( exacerbation	1/73 (1.4%)	1	0/67 (0%)	0
Hospitalized for severe aortic stenosis	0/73 (0%)	0	1/67 (1.5%)	1
Infections and infestations
Right stump infection	1/73 (1.4%)	1	0/67 (0%)	0
Wound infection	0/73 (0%)	0	1/67 (1.5%)	1
Nervous system disorders
Hospitalized for brain edema	1/73 (1.4%)	1	0/67 (0%)	0
Psychiatric disorders
Hospitalized for Altered Mental Status	0/73 (0%)	0	1/67 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Hospitalized for aspiration pneumonia	1/73 (1.4%)	1	0/67 (0%)	0
Hospitalization for pleural effusion	1/73 (1.4%)	1	0/67 (0%)	0
Surgical and medical procedures
Hospitalized for repair craninectomy	1/73 (1.4%)	1	0/67 (0%)	0
Amputation of the left 2nd toe	0/73 (0%)	0	1/67 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Insulin Glargine		Linagliptin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/73 (21.9%)		12/67 (17.9%)
Blood and lymphatic system disorders
Anemia	1/73 (1.4%)	1	0/67 (0%)	0
Cardiac disorders
Chest pain	0/73 (0%)	0	1/67 (1.5%)	1
Bradicardia	1/73 (1.4%)	1	0/67 (0%)	0
Hypotension	1/73 (1.4%)	1	0/67 (0%)	0
Gastrointestinal disorders
Nausea	0/73 (0%)	0	1/67 (1.5%)	1
Diarrhea	0/73 (0%)	0	1/67 (1.5%)	1
Musculoskeletal and connective tissue disorders
Fall	1/73 (1.4%)	1	1/67 (1.5%)	1
Renal and urinary disorders
Hematuria	0/73 (0%)	0	1/67 (1.5%)	1
Urinary Tract Infection	6/73 (8.2%)	6	3/67 (4.5%)	3
Acute Kidney Injury	0/73 (0%)	0	1/67 (1.5%)	1
Acute renal failure	3/73 (4.1%)	3	0/67 (0%)	0
Reproductive system and breast disorders
Penile infection	1/73 (1.4%)	1	0/67 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	2/73 (2.7%)	2	1/67 (1.5%)	1
Skin and subcutaneous tissue disorders
Shingels	0/73 (0%)	0	2/67 (3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.