Liraglutide Actions on the Liver: Effects on Glucose Phosphorylation

NCT02198209 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: U1111-1138-7223
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes is a chronic disease that has reached epidemic proportions. In order to improve our strategies for preventing and treating type 2 diabetes the investigators need to better understand the mechanism of this disease, and the way in which current therapies, such as the drug liraglutide, work to control blood sugar. It is known that liraglutide acts via increasing the secretion of the hormone insulin from the pancreas, hormone that in turn controls blood sugar. However, it is not known whether liraglutide also has actions on the liver. Animal studies have suggested that liraglutide might act by controlling the liver enzyme glucokinase (GCK), an enzyme that increases blood sugar uptake by the liver. This could be a crucial mechanism in which liraglutide controls blood sugar independently of insulin, thus making it beneficial not only in type 2 but also in type 1 diabetes. The effect of liraglutide on GCK activity has not been yet measured in humans. The investigators propose to investigate the acute and chronic effect of liraglutide on GCK by using a simple, widely used procedure (an IntraVenous Glucose Tolerance Test-IVGTT) and a novel approach (mathematical modeling of data obtained from this procedure), to assess GCK activity in people with type 2 diabetes. The investigators will first compare data obtained form 2 IVGTTs (with and without liraglutide) performed 1 week apart (acute effect). The investigators will then give liraglutide to patients for 6 weeks and do another IVGTT to measure GCK activity (chronic effects). Data obtained from this study will be used to further understand the mechanism of liraglutide action and how to better employ our current therapeutic options and develop new strategies for preventing and treating diabetes.

Conditions

Type 2 Diabetes

Keywords

liraglutide; GLP-1; liver glucokinase

Outcome Measures

Primary Outcomes (2)

• Liver glucokinase activity (acute effect)

  We will measure liver glucokinase (GCK) activity 'in vivo' during IVGTTs with and without liraglutide administration

  12 months

• Liver glucokinase activity (chronic effect)

  We will measure liver glucokinase (GCK) activity 'in vivo' during IVGTTs before and after 6 weeks of daily liraglutide administration

  12 months

Secondary Outcomes (2)

• insulin sensitivity

  12 months

• Acute insulin response to glucose and the disposition index

  12 months

Study Arms (1)

single arm

OTHER

Liraglutide (Victoza) 1. acute study: one injection of 0.6 mg s.c. before IVGTT 2. chronic study: 6 weeks of daily liraglutide administration (1 week at 0.6 mg, 1 week at 1.2 mg, 4 weeks at 1.8 mg, s.c).

Drug: Liraglutide

Interventions

Liraglutide DRUG

1. acute study: one injection of 0.6 mg s.c. before IVGTT 2. chronic study: 6 weeks of daily liraglutide administration (1 week at 0.6 mg, 1 week at 1.2 mg, 4 weeks at 1.8 mg, s.c).

Also known as: Victoza

single arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age (inclusive)
• Ability to provide informed consent before any trial-related activities
• Ability to communicate effectively with research staff
• Ability to return for follow up visit
• Adequate IV access
• If a female of childbearing potential, non-pregnant and taking reliable contraception
• Documented T2DM (per most recent American Diabetes Association criteria);
• Drug naïve or treated with metformin only;
• Diabetes should be well controlled (as defined by HbA1 ≤ 7.5%, FPG \<180 mg/dl).

You may not qualify if:

• Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
• Liver disease; history of alcoholism.
• Known or suspected allergy to liraglutide
• Contraindications to liraglutide: patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
• Patients with a history of pancreatitits
• Patients that have been treated with drugs that promote weight loss (e.g., Xenical® \[orlistat\], Meridia® \[sibutramine\], Acomplia® \[rimonabant\], Acutrim® \[phenylpropanolamine\], or similar over-the-counter medications) within 3 months of study start
• Patients that have been treated with diabetes drugs: injectables, (e.g GLP-1R agonists (Byetta® \[exenatide\], Victoza® \[liraglutide\]) amylin analogues; insulin and insulin analogues) or oral agents other than metformin (e.g.DPP-IV- inhibitors (Januvia® \[sitagliptin\], Onglyza® \[saxagliptin\] or Janumet® \[sitagliptin and metformin\]),insulin sensitizers (thiazolidindiones: pioglitazone \[Actos®\]); or sulfonylureas) within 3 months of study start.
• The receipt of any investigational drug within 3 months prior to study start.
• Type 1 diabetes

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Maturity-Onset Diabetes of the Young, Type 2

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Viorica Ionut, MD PhD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director, Diabetes & Obesity Research Institute

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: July 23, 2014
• Study Start: December 1, 2019
• Primary Completion: July 1, 2020
• Study Completion: December 1, 2020
• Last Updated: September 30, 2019

Record last verified: 2019-09

Locations

US (1)