Effects of Liraglutide on ER Stress in Obese Patients With Type 2 Diabetes

NCT02344186 | Unknown Phase 4

• 1 other identifier: 21440
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the study will be to test the hypothesis that treatment with Liraglutide will decrease ER stress and adipose tissue in obese patients with type 2 diabetes. Experimental Approach: The investigators will use a prospective, single blind, placebo controlled study design to study 12 obese patients with type 2 diabetes mellitus (T2DM). 6 patients will first receive Liraglutide for 24 weeks followed by placebo for 12 weeks. The other 6 patients will first receive placebo for 12 weeks followed by Liraglutide for 24 weeks. Measurements: The investigators will determine glycemic control (with HbA1c), body composition (bioelectric impedance analysis), insulin sensitivity (with hyperinsulinemic-euglycemic clamps), insulin secretion (with oral glucose tolerance testing), energy balance (calories in vs. calories out), plasma lipid levels and obtain subcutaneous fat biopsies to determine ER stress response markers before and after placebo and before and after Liraglutide treatment.

Conditions

Type 2 Diabetes

Keywords

diabetes, ER stress, glucagon-like peptide-1 analogs

Outcome Measures

Primary Outcomes (1)

• Changes in unfolded protein response markers

  Changes in unfolded protein response markers in adipose tissue biopsy samples. Specifically, the investigators will determine changes in mRNA (by RT-PCR) and protein (by Western blots) levels of the following ER stress markers: GRP78, ATF4, XBP-1s, PDI, calreticulin and calnexin.

  baseline, 6 months, 9 months

Secondary Outcomes (6)

• Insulin sensitivity

  baseline, 3 months, 6 months and 9 months

• Glucose control

  baseline, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months

• Energy expenditure

  baseline, 3 months, 6 months, 9 months

• Body weight

  baseline, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months

• Body composition

  baseline, 3 months, 6 months and 9 months

Study Arms (2)

Liraglutide

EXPERIMENTAL

Liraglutide will be started first with 0.6 mg/d for 1 week, then increased to 1.2 mg/d from week 2 to week 12, followed by 1.8 mg/d from week 12 to week 24.

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Subjects will receive placebo for 12 weeks.

Drug: Liraglutide

Interventions

Liraglutide DRUG

Crossover design - 24 weeks on active drug and 12 weeks daily placebo

Also known as: Victoza

Liraglutide; Placebo

Eligibility Criteria

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

You may qualify if:

• Patients with established type 2 diabetes, BMI 27-35, Age - 18-75 years, HbA1c 7-10%, patients treated with exercise, diet, metformin and/or alpha glucosidase inhibitors (all up to ½ of their maximal dose) or pioglitazone (up to 30 mg/d), ability to provide informed consent before any trial-related activities.

You may not qualify if:

• Patients with pancreatitis or a history of pancreatitis, patients with HbA1c \< 7% or \> 10%, type 2 diabetic patients treated with insulin, sulfonylureas, meglitinides, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) agonists or corticosteroids, patients with hypoglycemia unawareness and with impaired liver functions (≥ 2.5 times the upper normal limit), known or suspected allergy against liraglutide or contraindications to liraglutide (as specified in the product prescribing information), pregnancies, breastfeeding or intention of becoming pregnant or not using adequate contraceptive measures, patients with a personal or family history of medullary thyroid cancer and patients with Multiple Endocrine Neoplasia type 2.

Sponsors & Collaborators

• Temple University: lead

Study Sites (1)

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

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

• Ajaykumar D Rao, MD

  Temple University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: January 22, 2015
• Study Start: May 1, 2014
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: July 29, 2022

Record last verified: 2022-07

Locations

US (1)