The Effect of Liraglutide on Dietary Lipid Induced Insulin Resistance in Humans

NCT02403284 | Completed Phase 4

• 2 other identifiers: 0281593855
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

In this research study, investigators will test the effects of an approved medication for diabetes,Liraglutide, to reduce insulin resistance that develops from eating a diet high in saturated fats.

Conditions

Insulin Resistance

Keywords

insulin resistance; lipid metabolism; glucose metabolism; high fat diets

Outcome Measures

Primary Outcomes (1)

• Whole Body Insulin Sensitivity (insulin suppression test)

  An insulin suppression test will be measured before and approximately 3 weeks after each treatment phase. Key time frames for assessing steady state plasma glucose will be between 150 and 180 minutes during the insulin suppression test

  3 weeks

Secondary Outcomes (9)

• Postprandial lipid changes (area under the curve difference in triglyceride,total apolipoprotein B100, apolipoprotein B48, and apolipoprotein C3.

  3 weeks

• Postprandial changes in glucose metabolism (total and incremental area under the curve differences in glucose, insulin and glucagon)

  3 weeks

• Changes in adipose tissue insulin signaling pathway activation (compare insulin signaling pathway activity (e.g., Akt and insulin receptor phosphorylation)

  3 weeks

• subcutaneous adipose tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)

  3 weeks

• skeletal muscle tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)

  3 weeks

Study Arms (2)

Liraglutide

EXPERIMENTAL

Liraglutide titration up to 1.8 mg/d over approximately 3 weeks

Drug: Liraglutide

Sugar pill

PLACEBO COMPARATOR

matching placebo and titration

Drug: Sugar Pill

Interventions

Liraglutide DRUG

Subcutaneous injection by patient

Also known as: Victoza

Liraglutide

Sugar Pill DRUG

Subcutaneous injection daily

Also known as: Placebo

Sugar pill

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-75 years old
• Body mass index (BMI) from 22 to 35 kg/m2
• Normal glucose tolerance as determined by fasting blood glucose (\< 100 mg/dl) and 75 gm glucose load (2 hr glucose \<140 mg/dl)
• Fasting triglyceride levels ≥ 75 mg/dl and \<500 mg/dl

You may not qualify if:

• Type 1 or 2 diabetes mellitus or a hemoglobin A1c value \>6.5 mg/dl
• Any diabetes medications in the past month, thiazolidinedione medications in the prior 3 months or prior regular use of insulin
• Lactose intolerance or avoidance of dairy products
• Creatinine \> 2.0 mg/dl or other laboratory evidence of active disease, including hepatic enzyme elevation (AST or ALT) \> 2.5 x normal and anemia (Hct \< 35)
• Known 'Nonalcoholic Fatty Liver Disease'
• Malabsorption of fat or other nutrients, severe lactose intolerance or other significant gastrointestinal or pancreatic problems (including history of acute or chronic pancreatitis).
• Recent history of nausea or vomiting
• Acute bacterial or viral illness or evidence of other active infection in the past 4 weeks
• Prior cardiovascular event, stable or unstable angina or other major illness in the past 6 months
• Current regular use of anti-inflammatory medications or antioxidants in excess of a standard daily multi-vitamin, including over- the-counter medications and high dose salicylates (\> 1 gm/ day)
• Subjects receiving a lipid lowering medication must be on a stable dose for at least 6 weeks prior to participation.
• Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia 2
• Ethanol consumption more than 4 oz day
• Pregnancy, or lack of appropriate contraceptive use in premenopausal women (extremely rare in our older predominately male population)
• Poorly controlled hypertension, systolic blood pressure (SBP) \> 150 or diastolic blood pressure (DBP) \> 90 on 2 or more occasions during screening visits. Subjects receiving blood pressure medication will be on a stable dosing for at least 6 weeks prior to participation.

Sponsors & Collaborators

• Phoenix VA Health Care System: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Carl T. Hayden VA Medical Hospital

Phoenix, Arizona, 85012, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Liraglutide; Sugars

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Peter D Reaven, MD

  Carl T. Hayden Medical Research Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: March 31, 2015
• Study Start: March 1, 2013
• Primary Completion: April 28, 2021
• Study Completion: November 1, 2023
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)