Effects of Single Doses of Liraglutide and Dapagliflozin on Ketogenesis in Type 1 Diabetes

NCT ID: NCT02777073

Last Updated: 2024-02-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-01
• Study Completion Date: 2016-12-31

Brief Summary

1. To compare levels of ketone bodies (beta-hydroxybutyrate and acetoacetate) in plasma and urine following a single dose treatment of either liraglutide 1.8mg, dapagliflozin 10mg or placebo in insulinopenic state.

2. To compare plasma levels of free fatty acid, glucagon, hs-CRP, Ll-6 and IL-1 before and after administration of liraglutide/placebo.

Detailed Description

Diabetic ketoacidosis is an important cause of mortality and morbidity in type 1 patients. The decreased ratio of insulin to glucagon in insulin deficient subjects promotes ketogenesis. In patients with type 1 diabetes, the suppressive effect of hyperglycemia and the paracrine inhibitory effect of insulin and GABA from the β cell on α cell are absent. Thus, plasma glucagon concentrations are elevated and in combination with insulin deficiency, lead to lipolysis, increased plasma FFA concentrations and an increased fatty acid supply to the liver. Thus, both fatty acid oxidation and ketogenesis are enhanced.

Our recent work has shown that liraglutide, a GLP 1 agonist, improves glycemic control and reduces glycemic excursions in patients with type 1 diabetes within a few days of the initiation of treatment.

With this background, the investigators hypothesize that suppression of glucagon with liraglutide in patients with type 1 diabetes may protect them from lipolysis, increased bio-availability of FFAs, ketogenesis and ketoacidosis.

It is essential to investigate this area further as there are no prior studies that have investigated the acute effects of liraglutide on FFAs or ketogenesis. This study will be the first randomized controlled prospective study investigating the effect of liraglutide on ketogenesis. Also, it would be important to measure the mediators of inflammation at the same time to investigate whether there is a concomitant changes of inflammatory factors in parallel with the lipolysis and ketogenesis.

After the screening visit, subjects who meet the inclusion and exclusion criteria will be randomized to receive a single dose of either liraglutide, dapagliflozin or placebo and will be monitored for a total of 8 hours.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

liraglutide 1.8 mg

single dose of Victoza ( liraglutide) 1.8 mg

Group Type: ACTIVE_COMPARATOR

Victoza

Intervention Type: DRUG

Single dose of Liraglutide

Placebo

Single dose of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single dose of generic placebo

Dapagliflozin

Single dose of Dapagliflozin 10 mg oral tablet

Group Type: ACTIVE_COMPARATOR

Dapagliflozin 10mg Tab

Intervention Type: DRUG

single dose of 10 mg dapagliflozin

Interventions

Victoza

Single dose of Liraglutide

Intervention Type: DRUG

Placebo

Single dose of generic placebo

Intervention Type: DRUG

Dapagliflozin 10mg Tab

single dose of 10 mg dapagliflozin

Intervention Type: DRUG

Other Intervention Names

Liraglutide; Dapagliflozin

Eligibility Criteria

Inclusion Criteria

1. Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII, also known as insulin pump).

2. Undetectable c peptide (c-peptide < 0.1 ng/ml).

3. HbA1c of less than or equal to 8.5%.

4. Age 18-75 inclusive

Exclusion Criteria

1. Type 1 diabetes for less than 12 months

2. Coronary event/ procedure (MI, Unstable angina, CABG, PCI) in the last four weeks

3. Hepatic disease (Transaminase > 3 times normal) or Cirrhosis

4. Renal impairment (serum eGFR <30ml/min/1.73m2)

5. HIV or Hepatitis B or C positive status

6. History of pancreatitis, i.e., history of gallstones, alcohol abuse and hypertriglyceridemia

7. Pregnancy

8. Inability to give informed consent

9. History of Gastroparesis

10. Personal or Family History of medullary thyroid carcinoma or MEN 2 syndrome

11. Alcoholism

12. Hypertriglyceridemia (>500 mg/dl).

13. Those with history of bladder cancer , diabetic ketoacidosis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University at Buffalo

OTHER

Sponsor Role: lead

Responsible Party

Paresh Dandona

Distinguished Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

ECMC Ambulatory Center, 3rd Floor

Buffalo, New York, United States

Countries

United States

Other Identifiers

1974

Identifier Type: -

Identifier Source: org_study_id