Adding Liraglutide to High Dose Insulin: Breaking the Cycle

Ildiko Lingvay

Status and phase

Completed

Phase 4

Conditions

Type 2 Diabetes Mellitus

Obesity

Treatments

Drug: Liraglutide

Drug: Saline

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01505673

IIS-000235

Details and patient eligibility

About

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.

Full 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.

Enrollment

71 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.