Adding Liraglutide to High Dose Insulin: Breaking the Cycle

NCT01505673 | Completed Phase 4 Results DMC

• 1 other identifier: IIS-000235
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether the addition of liraglutide 1.8 mg/day to a high-dose insulin regimen (\>1.8 units/kg/day) in patients with uncontrolled (HbA1c \>7.5%) type 2 diabetes mellitus will improve blood sugar control. It also evaluates the effect of liraglutide on liver and pancreatic fat content, explores the mechanism of blood sugar improvement by assessing weight and pancreatic hormone release, and assesses blood pressure, lipid profile, and liver function. Finally it will look at patient quality of life and safety.

Conditions

Type 2 Diabetes Mellitus; Obesity

Keywords

Insulin; Glucagon-like peptide; Liraglutide; Beta-Cell; pancreatic steatosis; hepatic steatosis

Outcome Measures

Primary Outcomes (1)

• Glycemic Control Measured by HbA1c

  HbA1c (%)

  6-months

Secondary Outcomes (26)

• Pancreatic and Hepatic Triglyceride Content

  6-months

• Weight

  6-months

• Beta-Cell Function

  6-months

• Glucagon

  6-months

• Total Daily Insulin Dose

  6-months

Study Arms (2)

Liraglutide

ACTIVE COMPARATOR

Drug: Liraglutide

Saline injection

PLACEBO COMPARATOR

Drug: Saline

Interventions

Liraglutide DRUG

Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months

Also known as: Victoza

Liraglutide

Saline DRUG

Placebo injection of 1.8mg saline once daily for 6-months

Saline injection

Eligibility Criteria

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

You may qualify if:

• Type 2 diabetes mellitus
• Insulin dose of \>1.8 units/kg/day (represents total daily insulin dose, regardless of formulation, regimen, number of daily shots)
• HbA1c ≥ 7.5% and ≤ 11%
• Age ≥ 18
• Stable comorbidities on stable treatment regimens
• Stable dose of all oral hypoglycemics for ≥ 3 months prior to enrollment
• Ability to provide informed consent before any trial-related activities

You may not qualify if:

• Type 1 diabetes mellitus
• Any contraindication to the MRI procedure (metallic implants, severe claustrophobia, pregnancy, unable to lie still on a hard table for the duration of the procedure, weight above 400 lb - limit of the MRI table, magnet's inner circumference smaller than the largest body circumference)
• History of any pancreatic disease as it might interfere with the pancreatic TG measurement (i.e. pancreatitis, tumors, cysts, type 1 diabetes, any pancreatic surgery)
• End Stage Renal Disease on dialysis due to increased risk of hypoglycemia, and possible interference with accurate measurement of HbA1c
• Incretin therapy (any GLP-1 agonist or DPP-IV inhibitor)
• Unstable or decompensated comorbidities
• Personal or family history of medullary thyroid carcinoma or MEN-2 syndrome
• Severe gastroparesis
• Pregnancy, breast feeding, intention to become pregnant, or not using adequate contraceptive measures
• Organ transplant recipient or waiting list candidate
• Steroid use (current or potential use during the trial)
• Known/suspected allergy to trial medication, excipients, or related products
• Contraindications to study medications, worded specifically as stated in the product's prescribing information
• Non-English speaking volunteers since no interpreters are available and the safety of the volunteers could be jeopardized if adequate and reliable communication is not possible.

Sponsors & Collaborators

• Ildiko Lingvay: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

UT Southwestern

Dallas, Texas, 75390, United States

Location

Related Publications (2)

• Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):939-47. doi: 10.1001/jamainternmed.2016.1540.

  PMID: 27273731 DERIVED

• Vanderheiden A, Harrison LB, Warshauer JT, Adams-Huet B, Li X, Yuan Q, Hulsey K, Dimitrov I, Yokoo T, Jaster AW, Pinho DF, Pedrosa I, Lenkinski RE, Pop LM, Lingvay I. Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin. J Clin Endocrinol Metab. 2016 Apr;101(4):1798-806. doi: 10.1210/jc.2015-3906. Epub 2016 Feb 24.

  PMID: 26909799 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Insulin Resistance; Fatty Liver

Interventions

Liraglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Ildiko Lingvay
• Organization: University of Texas Southwestern Medical Center at Dallas

ildiko.lingvay@utsouthwestern.edu

214-648-2779

Study Officials

• Ildiko Lingvay, MD

  UT Southwestern

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 6, 2012
• Study Start: January 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: January 16, 2018
• Results First Posted: December 15, 2017

Record last verified: 2017-12

Locations

US (1)