LixiBIT: Feasibility of Once/Daily Administered GLP/1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin

• Sponsor: Medical University of Vienna (Other)
• Overall Status: Completed
• CT.gov ID: NCT02168491
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Premixed insulin-based therapy is a standard insulin treatment strategy in Austria. The widespread use of premixed insulin is explained by high acceptance by health care professionals and patients due to one single product and flexible number of injections (1-3 daily) which covers the demand in controlling fasting and postprandial glucose excursions of most patients with diabetes. However, the use of pre-mixed insulin frequently leads to a high insulin demand and consequently weight gain and an increased risk of hypoglycemia. Hence, achieve good metabolic control in these patients remains a major challenge.

For those patients, the approach to treatment intensification without facing the typical risks of insulin treatment (hypoglycemia and weight increase) is of major importance. One, so far not exploited option may be the BIT-strategy: Basal insulin in combination with incretin-based therapy.

Pathophysiologically basal insulin inhibits glucose production in the liver, decreases hepatic insulin resistance and improves the function of beta cells in the postprandial state by discharge of fasting insulin secretion. During further diabetes progression steadily increasing HbA1c levels - despite good fasting blood glucose control - indicate the need for additional intervention of meal-related glucose excursions. In this stage of type-2 diabetes basal insulin can be combined with prandial (short-acting) insulin or prandial GLP-1 receptor agonists. However, regarding important safety parameters: risks of hypoglycemia and weight gain in the long-term treatment GLP-1 receptor agonists are beneficial.

Lixisenatide is a novel GLP-1 receptor agonist with a pronounced postprandial (PPG) effect which fits with basal insulin mode of action primarily focused on fasting blood glucose reduction.

Therefore 10 patients (both gender) under treatment with premixed insulin (2-3 times daily) and HbA1c>7% will be switched to basal insulin glargine (Lantus, once daily) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily). The investigators hypothesize that switching from a therapy based on premixed insulin to a simple, once daily administered combination of basal insulin plus a GLP-1 receptor agonist in patients with type-2 diabetes not achieving therapeutic target (HbA1c>7%) is clinically feasable in an out patient setting

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Lixisenatide; Drug: Insulin glargine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Feasibility of Once-daily Administered GLP-1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin in Patients With Type-2 Diabetes Mellitus Not Achieving Therapeutic Targets With Premixed Insulin
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intervention group 10 type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide

Drug: Lixisenatide; Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist.; Other Names: Lyxumia ; Drug: Insulin glargine; Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist.; Other Names: Lantus

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c From Baseline to End [12 weeks]

   A change between two time points is reported. Time Frame: baseline and 12 weeks.

Secondary Outcome Measures

1. Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks) [12 weeks]

   Patients will be instructed to record all insulin injections and a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) during a one-week prestudy run-in period to confirm compliance and document current metabolic control and doses of premixed insulin. Patients will be asked to record not only glucose profiles (at least 4 measurements per day) but also the occurrence of hypoglycemic symptoms or other adverse effects daily throughout the study. During the last week of the study patients will be asked to again record a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) and drug injections to confirm compliance and document metabolic control.

2. Change in Body Weight From Baseline to End of Study [12 weeks]

   A change between two time points is reported. Time Frame: baseline and 12 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 - 70a

• Subjects understand study related activities and give written informed concent

• HbA1c between 7 - 10 % under treatment with premixed insulin (2-3 injections)

Exclusion Criteria:

• Females of child-bearing age

• History of hypoglycemia unawareness

• Gastrointestinal disease associated with prolonged nausea and vomiting

• Impaired liver function (transaminase >2x than normal)

• Impaired kidney function (creatinin > 1,2 mg/dl)

• Known intolerance against GLP-1 receptor agonists

• History of pancreatitis or pancreas tumor

• Malignancies, autoimmune diseases

• Severe dyslipidemia (serum triglycerides > 400 mg/dl, cholesterol > 300 mg/dl)

• Psychiatric disorder

• Oral glucose lowering medication except for metformin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University Of Vienna, Department of Internal Medicine III	Vienna		Austria	1090

Sponsors and Collaborators

• Medical University of Vienna

Investigators

• Principal Investigator: Michael Krebs, MD, Prof., Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prof. Dr. Michael Krebs, Prof. MD, Medical University of Vienna
• ClinicalTrials.gov Identifier: NCT02168491
• Other Study ID Numbers: LixiBIT_V3; 2013-005334-37
• First Posted: Jun 20, 2014
• Last Update Posted: May 9, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Glargine; Lixisenatide

Study Results

Participant Flow

Recruitment Details	11 patients were screened
Pre-assignment Detail	2 patients declined to participate because of time restraints, thus study medication was administered in 9 patients

Arm/Group Title	Lixisenatide With Basal Insulin (LixiBIT)
Arm/Group Description	Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide Lixisenatide: Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist. Insulin glargine: Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of
Period Title: Overall Study
STARTED	9
COMPLETED	8
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Lixisenatide With Basal Insulin (LixiBIT)
Arm/Group Description	Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.6 (6.0)
Sex: Female, Male (Count of Participants)
Female	3 33.3%
Male	6 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	9 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Austria	9 100%

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c From Baseline to End
Description	A change between two time points is reported. Time Frame: baseline and 12 weeks.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lixisenatide With Basal Insulin (LixiBIT)
Arm/Group Description	Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide
Measure Participants	9
Mean (Standard Deviation) [HbA1c in percent]	-0.54 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lixisenatide With Basal Insulin (LixiBIT)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.02
	Comments
	Method	paired t test
	Comments

2. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks)
Description	Patients will be instructed to record all insulin injections and a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) during a one-week prestudy run-in period to confirm compliance and document current metabolic control and doses of premixed insulin. Patients will be asked to record not only glucose profiles (at least 4 measurements per day) but also the occurrence of hypoglycemic symptoms or other adverse effects daily throughout the study. During the last week of the study patients will be asked to again record a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) and drug injections to confirm compliance and document metabolic control.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lixisenatide With Basal Insulin (LixiBIT)
Arm/Group Description	Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide
Measure Participants	9
Mean (95% Confidence Interval) [glucose in mg/dl]	-9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lixisenatide With Basal Insulin (LixiBIT)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	paired t test
	Comments

3. Secondary Outcome

Title	Change in Body Weight From Baseline to End of Study
Description	A change between two time points is reported. Time Frame: baseline and 12 weeks.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lixisenatide With Basal Insulin (LixiBIT)
Arm/Group Description	Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide
Measure Participants	9
Mean (Standard Deviation) [weight in kg]	-1.4 (3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lixisenatide With Basal Insulin (LixiBIT)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	paired t test
	Comments

Adverse Events

Arm/Group Title	Lixisenatide With Basal Insulin (LixiBIT)
Arm/Group Description	Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide
All Cause Mortality
	Lixisenatide With Basal Insulin (LixiBIT)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lixisenatide With Basal Insulin (LixiBIT)
	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)
Surgical and medical procedures
elective ENT surgery	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Lixisenatide With Basal Insulin (LixiBIT)
	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)
Endocrine disorders
mild asymptomatic hypoglycaemia	3/9 (33.3%)	8
symptomatic hypoglycaemia	1/9 (11.1%)	1
hypercholesterolaemia	2/9 (22.2%)	2
Eye disorders
elective ambulatory cataract surgery	1/9 (11.1%)	1
Gastrointestinal disorders
mild gastrointestinal complaints	2/9 (22.2%)	3
General disorders
cough	1/9 (11.1%)	1
Infections and infestations
urinary tract infection	2/9 (22.2%)	3
Musculoskeletal and connective tissue disorders
shoulder pain	1/9 (11.1%)	1
Renal and urinary disorders
haematuria	1/9 (11.1%)	1

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.