Adding Liraglutide to High Dose Insulin: Breaking the Cycle

NCT ID: NCT01505673

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2016-06-30

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.

Detailed Description

Type 2 diabetes is a progressive disease with incessant beta-cell dysfunction that often ultimately requires insulin treatment. Patients requiring high insulin dosages represent a particular treatment challenge and often have uncontrolled glycemia despite progressive dose increases and are especially prone to insulin related lipotoxicity and weight gain.

Glucagon-like peptide agonists (GLP-1) such as liraglutide have many actions that position them to break the vicious cycle in this population through the following mechanisms: (1) weight loss; (2) improved hepatic steatosis; (3) improved pancreatic steatosis; (4) decreased glucagon levels; (5) improved beta-cell function.

The purpose of the study is to demonstrate that liraglutide is both effective and safe when added to a high dose insulin treatment regimen. Liraglutide will improve glycemic control, weight, metabolic parameters, as well as patient satisfaction, with minimal adverse events. The study also proposes to study the mechanisms through which such improvements might occur, especially beta-cell function, glucagon levels, and hepatic and pancreatic fat content.

Conditions

Type 2 Diabetes Mellitus; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Liraglutide

Group Type: ACTIVE_COMPARATOR

Liraglutide

Intervention Type: DRUG

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

Saline injection

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

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

Interventions

Liraglutide

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

Intervention Type: DRUG

Saline

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

Intervention Type: DRUG

Other Intervention Names

Victoza

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Ildiko Lingvay

OTHER

Sponsor Role: lead

Responsible Party

Ildiko Lingvay

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ildiko Lingvay, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern

Locations

UT Southwestern

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27273731 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26909799 (View on PubMed)

Other Identifiers

IIS-000235

Identifier Type: -

Identifier Source: org_study_id