Effect of Liraglutide on Epicardial Fat in Subjects With Type 2 Diabetes

• Sponsor: University of Miami (Other)
• Overall Status: Completed
• CT.gov ID: NCT02014740
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

The purpose of this research study is to learn about the effect of Liraglutide, (Victoza®), on the fat surrounding the heart.Excessive amount of the fat around the heart is common in people with type 2 diabetes and can be associated with poor sugar control. Liraglutide is an injectable prescription medicine that can improve blood sugar control in adults with type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes; Overweight; Obesity	Drug: Liraglutide; Drug: Metformin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Liraglutide on Epicardial Fat in Subjects With Type 2 Diabetes
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liraglutide • L-group will be started and dose-escalated to 1.8mg sc once daily according to below schedule: Liraglutide will be administered with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). L-group subjects will need to achieve the final dose of 1.8 mg by at least three weeks from the starting dose. Subjects who would not be able to achieve the dose of 1.8 mg (due to potential side effects) will be advised to lower the dose to 1.2 mg. Metformin regimen will be continued.	Drug: Liraglutide; Liraglutide (Victoza) is an acylated analogue of glucagon-like peptide-1 (GLP-1) indicated for the treatment of type 2 diabetes mellitus• L-group will be started and dose-escalated to 1.8mg sc once daily according to below schedule: Liraglutide will be administered with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). L-group subjects will need to achieve the final dose of 1.8 mg by at least three weeks from the starting dose. Subjects who would not be able to achieve the dose of 1.8 mg (due to potential side effects) will be advised to lower the dose to 1.2 mg. Metformin regimen will be continued. .; Drug: Metformin
Active Comparator: Metformin M-group will be treated with Metformin for the duration of the study. Metformin (from 500 mg twice daily to a maximum of 1000 mg twice daily) regimen will be continued to achieve fasting glucose between 80 and 140 mg/dl	Drug: Metformin

Outcome Measures

Primary Outcome Measures

1. Echocardiographic Epicardial Fat Thickness [6 months]

   Echocardiographic epicardial fat thickness is an non invasive, inexpensive, reproducible and direct measure of visceral fat. In fact, epicardial fat strongly reflects the intra-abdominal and intra-myocardial fat accumulation as measured by magnetic resonance imaging procedures.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes, as defined by ADA criteria

• HbA1c < 8% measured at least 1 month prior to this study

• BMI ≥27 kg/m2

• Pre-treatment with Metformin

• Age > 18 and < 65 years old

Exclusion Criteria:

• • Known contra-indications to Liraglutide, such as previous history of pancreatitis or medullary thyroid carcinoma, personal or family history of MEN, in accordance with risks and safety information included in the latest updated Prescribing Information for Victoza®

• Type 1 diabetes, as defined by American Diabetes Association (ADA) criteria

• Insulin dependent or treated type 2 diabetes

• Current use of other injectable incretins

• History of diabetes ketoacidosis

• Advanced Chronic Kidney Disease, as defined by Glomerular Filtration Rate (GFR) < 30 mL/min/1.73m2

• Clinical signs or symptoms of New York Heart Association (NYHA) class III-IV heart failure

• Clinical or laboratory evidences of chronic active liver diseases

• Acute or chronic infective diseases

• Cancer or chemotherapy

• Current use of systemic corticosteroids or in the 3 months prior this study

• Known or suspected allergy to Liraglutide, excipients, or related products

• Pregnant, breast-feeding or the intention of becoming pregnant

• Females of childbearing potential who are not using adequate contraceptive methods

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Dec 5, 2017

More Information

Publications

None provided.

• Responsible Party: Gianluca Iacobellis, Professor of Clinical Medicine, University of Miami
• ClinicalTrials.gov Identifier: NCT02014740
• Other Study ID Numbers: 20120811
• First Posted: Dec 18, 2013
• Last Update Posted: Jun 6, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Gianluca Iacobellis, Professor of Clinical Medicine, University of Miami: Epicardial fat; Type 2 diabetes; Obesity; GLP-1 analogs
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight; Metformin; Liraglutide

Study Results

Participant Flow

Arm/Group Title	Liraglutide	Metformin
Arm/Group Description	L-group will be started and dose-escalated to 1.8mg sc once daily according to below schedule: Liraglutide will be administered with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). L-group subjects will need to achieve the final dose of 1.8 mg by at least three weeks from the starting dose. Subjects who would not be able to achieve the dose of 1.8 mg (due to potential side effects) will be advised to lower the dose to 1.2 mg. Metformin regimen will be continued.	M-group will be treated with Metformin for the duration of the study. Metformin (from 500 mg twice daily to a maximum of 1000 mg twice daily) regimen will be continued to achieve fasting glucose between 80 and 140 mg/dl Metformin
Period Title: Overall Study
STARTED	55	45
COMPLETED	49	40
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Liraglutide	Metformin	Total
Arm/Group Description	• L-group will be started and dose-escalated to 1.8mg sc once daily according to below schedule: Liraglutide will be administered with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). L-group subjects will need to achieve the final dose of 1.8 mg by at least three weeks from the starting dose. Subjects who would not be able to achieve the dose of 1.8 mg (due to potential side effects) will be advised to lower the dose to 1.2 mg. Metformin regimen will be continued.	M-group will be treated with Metformin for the duration of the study. Metformin (from 500 mg twice daily to a maximum of 1000 mg twice daily) regimen will be continued to achieve fasting glucose between 80 and 140 mg/dl Metformin	Total of all reporting groups
Overall Participants	55	45	100
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	55 100%	45 100%	100 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (10)	52 (10)	50.8 (10)
Sex: Female, Male (Count of Participants)
Female	33 60%	28 62.2%	61 61%
Male	22 40%	17 37.8%	39 39%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 38.2%	17 37.8%	38 38%
Not Hispanic or Latino	34 61.8%	28 62.2%	62 62%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	55 100%	45 100%	100 100%
Epicardial adipose tissue Thickness (EAT) (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	9.6 (2)	7.4 (1.6)	8.75 (1.9)
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	37.8 (7)	32.6 (6)	35.2 (6)
HemoglobinA1c (HbA1c) (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	6.6 (0.8)	6.4 (0.6)	6.52 (0.6)

Outcome Measures

1. Primary Outcome

Title	Echocardiographic Epicardial Fat Thickness
Description	Echocardiographic epicardial fat thickness is an non invasive, inexpensive, reproducible and direct measure of visceral fat. In fact, epicardial fat strongly reflects the intra-abdominal and intra-myocardial fat accumulation as measured by magnetic resonance imaging procedures.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liraglutide	Metformin
Arm/Group Description	• L-group will be started and dose-escalated to 1.8mg sc once daily according to below schedule: Liraglutide will be administered with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). L-group subjects will need to achieve the final dose of 1.8 mg by at least three weeks from the starting dose. Subjects who would not be able to achieve the dose of 1.8 mg (due to potential side effects) will be advised to lower the dose to 1.2 mg. Metformin regimen will be continued.	M-group will be treated with Metformin for the duration of the study. Metformin (from 500 mg twice daily to a maximum of 1000 mg twice daily) regimen will be continued to achieve fasting glucose between 80 and 140 mg/dl Metformin
Measure Participants	55	45
Baseline	9.6 (2)	7.4 (1.6)
3-month	6.8 (1.5)	7.5 (1.5)
6-month	6.2 (1.5)	6.9 (1.5)

Adverse Events

Time Frame	6 months
Arm/Group Title	Liraglutide		Metformin
Arm/Group Description	L-group will be started and dose-escalated to 1.8mg sc once daily according to below schedule: Liraglutide will be administered with a starting dose of 0.6 mg (after a least one week) and subsequent increments to 1.2 mg (after a least one week) and to 1.8 mg (after at least a week on 1.2 mg). L-group subjects will need to achieve the final dose of 1.8 mg by at least three weeks from the starting dose. Subjects who would not be able to achieve the dose of 1.8 mg (due to potential side effects) will be advised to lower the dose to 1.2 mg. Metformin regimen will be continued.		M-group will be treated with Metformin for the duration of the study. Metformin (from 500 mg twice daily to a maximum of 1000 mg twice daily) regimen will be continued to achieve fasting glucose between 80 and 140 mg/dl Metformin
All Cause Mortality
	Liraglutide		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/45 (0%)
Serious Adverse Events
	Liraglutide		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/45 (0%)
Other (Not Including Serious) Adverse Events
	Liraglutide		Metformin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/55 (29.1%)		12/45 (26.7%)
Gastrointestinal disorders
nausea	16/55 (29.1%)		12/45 (26.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.