Effects of Single Doses of Liraglutide and Dapagliflozin on Ketogenesis in Type 1 Diabetes (1974)

February 3, 2024 updated by: Paresh Dandona, University at Buffalo

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

  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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14215
        • ECMC Ambulatory Center, 3rd Floor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: liraglutide 1.8 mg
single dose of Victoza ( liraglutide) 1.8 mg
Drug: Victoza
Single dose of Liraglutide
Other Names:
  • Liraglutide
Placebo Comparator: Placebo
Single dose of placebo
Drug: Placebo
Single dose of generic placebo
Active Comparator: Dapagliflozin
Single dose of Dapagliflozin 10 mg oral tablet
Drug: Dapagliflozin 10mg Tab
single dose of 10 mg dapagliflozin
Other Names:
  • Dapagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin
Time Frame: 8 hours
To compare levels of ketone bodies beta-hydroxybutyrate in plasma following a single dose treatment of either liraglutide 1.8mg,dapagliflozin 10mg or placebo in insulinopenic state.
8 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Glucagon Levels.
Time Frame: 8 hours
This secondary endpoint compares change in glucagon concentrations (in pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo
8 hours
Change in Free Fatty Acid (FFA) Concentrations
Time Frame: 8 hours
This secondary endpoint compares the change in FFA concentrations (mM) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo
8 hours
Change in Ghrelin Concentrations
Time Frame: 8 Hours
This secondary endpoint compares the change in ghrelin concentrations (pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo
8 Hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University at Buffalo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 31, 2016

Study Registration Dates

First Submitted

December 1, 2015

First Submitted That Met QC Criteria

May 16, 2016

First Posted (Estimated)

May 19, 2016

Study Record Updates

Last Update Posted (Estimated)

February 29, 2024

Last Update Submitted That Met QC Criteria

February 3, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1974

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 1 Diabetes

Clinical Trials on Victoza

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Latvia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe