Cooperation of Insulin and GLP-1 on Myocardial Glucose Uptake

NCT ID: NCT01232946

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2017-09-08

Brief Summary

27 Type 2 diabetic subjects (HbA1c 7.5 - 9.5%) currently treated with diet and exercise alone or with oral antidiabetic agents will be randomly assigned to one of three treatment groups: insulin detemir, liraglutide, or liraglutide plus detemir (9 subjects per group), on a background of metformin 2000 mg per day. After 3 months' treatment, PET measurements of myocardial fuel selection will take place, under fasting conditions in the morning following that day's treatment injection(s).

Detailed Description

The investigators will test the hypothesis that effects of liraglutide plus insulin detemir on myocardial fuel selection will be greater than the effects of either agent alone. 27 Type 2 diabetic subjects (HbA1c 7.5 - 9.5%) currently treated with diet and exercise alone or with oral antidiabetic agents will be randomly assigned to one of three treatment groups: insulin detemir, liraglutide, or liraglutide plus detemir (9 subjects per group). All subjects will undergo an initial standardization of background treatment to metformin 2000 mg per day, followed by randomized assignment to 3 months' treatment with liraglutide 1.8 mg/day (once daily each morning, tapering up according to label instructions) and/or detemir (administered twice daily, initially at 10 units per day then titrated to achieve fasting morning glucose readings below 130 mg/dL). PET measurements of myocardial fuel selection will take place at the end of this treatment period, under fasting conditions in the morning following that day's treatment injection(s).

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Iiraglutide

Type 2 diabetic subjects will be assigned to 3 months of treatment with 1.8mg liraglutide administered once daily in addition to background metformin 2000mg/day. PET measurements of myocardial glucose uptake will take place at the end of treatment.

Group Type: EXPERIMENTAL

liraglutide

Intervention Type: DRUG

1.8mg subcutaneous qd for 3 months

insulin detemir

Type 2 diabetic subjects will be assigned to 3 months of treatment with insulin detemir administered twice daily in addition to background metformin 2000mg/day. PET measurements of myocardial glucose uptake will take place at the end of treatment.

Group Type: EXPERIMENTAL

insulin detemir

Intervention Type: DRUG

5units subcutaneous bid titrated to fasting glucose of \<130mg/dL for 3 months

Liraglutide plus insulin detemir

Type 2 diabetic subjects will be assigned to 3 months of treatment with a combination of liraglutide and insulin detemir in addition to background metformin 2000mg/day. PET measurements of myocardial glucose uptake will take place at the end of treatment.

Group Type: EXPERIMENTAL

liraglutide plus insulin detemir

Intervention Type: DRUG

liraglutide 1.8mg subq qd plus insulin detemir 5units bid titrated to fasting blood glucose \<130mg/dL for 3 months.

Interventions

liraglutide

1.8mg subcutaneous qd for 3 months

Intervention Type: DRUG

insulin detemir

5units subcutaneous bid titrated to fasting glucose of \<130mg/dL for 3 months

Intervention Type: DRUG

liraglutide plus insulin detemir

liraglutide 1.8mg subq qd plus insulin detemir 5units bid titrated to fasting blood glucose \<130mg/dL for 3 months.

Intervention Type: DRUG

Other Intervention Names

Victoza; Levemir; Vyctoza plus Levemir

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetic
• 18-50 years
• BMI > 25kg/m2
• HbA1c 7.0-10.0%
• Treated with up to 2 oral agents

Exclusion Criteria

• Chronic illness or infection (other than diabetes mellitus)
• Known coronary artery disease, structural heart disease or abnormal ECG on screen.
• Treatment with >2 antihypertensive agents or blood pressure >140/95 on two occasions during screening
• History of claustrophobia, musculoskeletal or other factors which would result in an inability to comfortably remain within the PET scanner gantry for the duration of the imaging protocol.
• Occupational, investigational or other known radiation exposure which together with the planned radiologic studies, will result in greater than 500 mrem total exposure in a 12 month period.
• Current pregnancy
• Treatment with GLP-1 agonist or DPP4 inhibitor within the past 6 months
• Known intolerance to GLP-1 agonist
• Personal history of pancreatitis, personal or family history of medullary thyroid carcinoma, or other contraindications to liraglutide treatment.
• Recognized microvascular complications (neuropathy, nephropathy, retinopathy).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Kieren Mather

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kieren J Mather, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana Clinical Research Center

Indianapolis, Indiana, United States

Countries

United States

References

Mather KJ, Considine RV, Hamilton L, Patel NA, Mathias C, Territo W, Goodwill AG, Tune JD, Green MA, Hutchins GD. Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection vs. Insulin Alone in Type 2 Diabetes. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3456-3465. doi: 10.1210/jc.2018-00712.

Reference Type: DERIVED

PMID: 30020461 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1105005578

Identifier Type: -

Identifier Source: org_study_id