Trial Outcomes & Findings for Liraglutide Effects on Epicardial Fat Inflammatory Genes (NCT NCT03260881)

Results Overview

EAT adipogenesis and inflammation as measured by miRNA expression (miR16-miR155-miR181a), from peri-coronary EAT samples collected during CABG after up to 12 weeks of treatment with either liraglutide or placebo. Tumor Necrosis Factor (TNF)-Alpha and Interleukin (IL)-6 gene expression were also measured in a subsample of peri-coronary EAT samples. miRNA and gene expression will be expressed as cycle threshold (ct) units. The PCR ct (cycle threshold) value refers to the number of cycles needed to replicate enough RNA to be detected.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

38 participants

Primary outcome timeframe

Up to 12 weeks

Results posted on

2025-07-08

Participant Flow

Participants were recruited among the outpatient population who routinely referred to the University of Miami, Division of Cardiothoracic Surgery, and/or the Division and/or Division of Endocrinology, Diabetes and Metabolism outpatient clinics who required elective coronary artery bypass graft (CABG) surgery regardless of their participation in the study during COVID-19 pandemic

Participant milestones

Participant milestones
Measure	Study Group Study group was started on liraglutide in addition to current standard treatment for diabetes and CAD for a minimum of 4 weeks up to 12 weeks prior to CABG 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), or maximum tolerated dose (MTD).	Control Group Control group received placebo pens in addition to current treatment for a minimum of 4 weeks up to 12 weeks prior to the CABG 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). Patients continued placebo up to the day before CABG
Overall Study STARTED	19	19
Overall Study COMPLETED	19	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Group n=19 Participants Study group was started on liraglutide in addition to current standard treatment for diabetes and CAD for a minimum of 4 weeks up to 12 weeks prior to CABG 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), or maximum tolerated dose (MTD).	Control Group n=19 Participants Control group received placebo pens in addition to current treatment for a minimum of 4 weeks up to 12 weeks prior to the CABG 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). Patients continued placebo up to the day before CABG	Total n=38 Participants Total of all reporting groups
Age, Continuous	63.7 years STANDARD_DEVIATION 7 • n=19 Participants	65 years STANDARD_DEVIATION 11 • n=19 Participants	64.5 years STANDARD_DEVIATION 9.5 • n=38 Participants
Sex: Female, Male Female	4 Participants n=19 Participants	4 Participants n=19 Participants	8 Participants n=38 Participants
Sex: Female, Male Male	15 Participants n=19 Participants	15 Participants n=19 Participants	30 Participants n=38 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Body Mass Index (BMI)	32.7 kg/m^2 STANDARD_DEVIATION 6.1 • n=19 Participants	32.1 kg/m^2 STANDARD_DEVIATION 6.8 • n=19 Participants	32.4 kg/m^2 STANDARD_DEVIATION 6.4 • n=38 Participants
Hemoglobin A1c (HbA1c)	6.9 %HbA1C STANDARD_DEVIATION 1.1 • n=19 Participants	7.2 %HbA1C STANDARD_DEVIATION 1.3 • n=19 Participants	7 %HbA1C STANDARD_DEVIATION 1.2 • n=38 Participants

PRIMARY outcome

Timeframe: Up to 12 weeks

Population: EAT fat samples could not be collected in 8 patients (5 in the liraglutide group and 3 in the placebo group) due to surgical circumstances and surgeon's decision during the CABG and in 2 patients (1 in the liraglutide and 1 in the placebo group) who eventually decided not to have surgery despite the clinical indications.

EAT adipogenesis and inflammation as measured by miRNA expression (miR16-miR155-miR181a), from peri-coronary EAT samples collected during CABG after up to 12 weeks of treatment with either liraglutide or placebo. Tumor Necrosis Factor (TNF)-Alpha and Interleukin (IL)-6 gene expression were also measured in a subsample of peri-coronary EAT samples. miRNA and gene expression will be expressed as cycle threshold (ct) units. The PCR ct (cycle threshold) value refers to the number of cycles needed to replicate enough RNA to be detected.

Outcome measures

Outcome measures
Measure	Study Group n=13 Participants Study group was started on liraglutide in addition to current standard treatment for diabetes and CAD for a minimum of 4 weeks up to 12 weeks prior to CABG 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), or maximum tolerated dose (MTD).	Control Group n=15 Participants Control group received placebo pens in addition to current treatment for a minimum of 4 weeks up to 12 weeks prior to the CABG 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). Patients continued placebo up to the day before CABG
EAT Inflammation miR16	0.70 ct (cycle threshold) Standard Deviation 0.60	1.4 ct (cycle threshold) Standard Deviation 2.3
EAT Inflammation miR155	0.39 ct (cycle threshold) Standard Deviation 0.42	0.25 ct (cycle threshold) Standard Deviation 0.43
EAT Inflammation miR181-a	0.32 ct (cycle threshold) Standard Deviation 0.42	0.25 ct (cycle threshold) Standard Deviation 0.43
EAT Inflammation IL6	0.8 ct (cycle threshold) Standard Deviation 0.16	0.5 ct (cycle threshold) Standard Deviation 0.14
EAT Inflammation TNF-a	0.57 ct (cycle threshold) Standard Deviation 0.14	0.12 ct (cycle threshold) Standard Deviation 0.05

SECONDARY outcome

Timeframe: Baseline and up to 12 weeks

Population: EAT thickness ultrasound measurement could not be performed after the CABG due to COVID-19 hospital restrictions

Change from baseline in EAT thickness as measured via ultrasound in mm

Outcome measures

Outcome measures
Measure	Study Group n=19 Participants Study group was started on liraglutide in addition to current standard treatment for diabetes and CAD for a minimum of 4 weeks up to 12 weeks prior to CABG 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), or maximum tolerated dose (MTD).	Control Group n=19 Participants Control group received placebo pens in addition to current treatment for a minimum of 4 weeks up to 12 weeks prior to the CABG 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). Patients continued placebo up to the day before CABG
EAT Thickness	11.8 mm Standard Deviation 2.1	10 mm Standard Deviation 2

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: Fat samples could not be collected in 8 patients (5 in the liraglutide group and 3 in the placebo group) due to surgical circumstances and surgeon's decision during the CABG and in 2 patients (1 in the liraglutide and 1 in the placebo group) who eventually decided not to have surgery despite the clinical indications.

SAT adipogenesis and inflammation as measured by miRNA expression (miR16-miR155-miR181a), from SAT samples collected during CABG after up to 12 weeks of treatment with either liraglutide or placebo. miRNA will be expressed as cycle threshold (ct) units. The PCR ct (cycle threshold) value refers to the number of cycles needed to replicate enough RNA to be detected.

Outcome measures

Outcome measures
Measure	Study Group n=13 Participants Study group was started on liraglutide in addition to current standard treatment for diabetes and CAD for a minimum of 4 weeks up to 12 weeks prior to CABG 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), or maximum tolerated dose (MTD).	Control Group n=15 Participants Control group received placebo pens in addition to current treatment for a minimum of 4 weeks up to 12 weeks prior to the CABG 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). Patients continued placebo up to the day before CABG
SAT Inflammation miR16	0.08 ct (cycle threshold) Standard Deviation 0.11	0.17 ct (cycle threshold) Standard Deviation 0.36
SAT Inflammation miR155	0.06 ct (cycle threshold) Standard Deviation 0.11	0.04 ct (cycle threshold) Standard Deviation 0.07
SAT Inflammation miR181a	0.12 ct (cycle threshold) Standard Deviation 0.24	0.07 ct (cycle threshold) Standard Deviation 0.16

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: Data was not collected due to due to technical difficulties and decision of the cardiac surgeon during the CABG surgery.

Gene expression of receptors or GLP-1 within EAT, expressed as cycle threshold (ct) units. The PCT Ct (cycle threshold) value refers to the number of cycles needed to replicate enough RNA to be detected

Outcome measures

Outcome data not reported

Adverse Events

Study Group

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Control Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Study Group n=19 participants at risk Study group was started on liraglutide in addition to current standard treatment for diabetes and CAD for a minimum of 4 weeks up to 12 weeks prior to CABG 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), or maximum tolerated dose (MTD).	Control Group n=19 participants at risk Control group received placebo pens in addition to current treatment for a minimum of 4 weeks up to 12 weeks prior to the CABG 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). Patients continued placebo up to the day before CABG
Gastrointestinal disorders nausea	31.6% 6/19 • patients were followed up to 12 weeks from enrollment to the day of the CABG surgery	10.5% 2/19 • patients were followed up to 12 weeks from enrollment to the day of the CABG surgery
Gastrointestinal disorders abdominal distention	31.6% 6/19 • patients were followed up to 12 weeks from enrollment to the day of the CABG surgery	10.5% 2/19 • patients were followed up to 12 weeks from enrollment to the day of the CABG surgery

Additional Information

Dr Gianluca Iacobellis MD PhD Professor of Medicine

University of Miami Miller School of Medicine

Phone: 3052433636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place