Liraglutide Treatment to Patients With Severe Renal Insufficiency

Condition(s) targeted: Type 2 Diabetes Mellitus; End-stage Renal Disease

Intervention: Liraglutide (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Bo Feldt-Rasmussen

Official(s) and/or principal investigator(s):
Bo Feldt-Rasmussen, Prof, DMSc, Study Director, Affiliation: Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
Thomas Idorn, MD, Principal Investigator, Affiliation: Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet

Overall contact:
Thomas Idorn, MD, Phone: +45 3545 1098, Email: thomas.idorn@rh.regionh.dk

Incretin-based therapy for the treatment of patients with type 2 diabetes mellitus (T2D) is new and fundamentally different from the classical treatments with oral antidiabetic agents and insulin. The novel and original aspect of this investigator-initiated study is the focus on treatment with an incretin-based agent (the GLP-1 analogue liraglutide) in T2D patients with severely reduced kidney function. At present there is virtually no knowledge of the physiology and clinical implications of the role of incretin hormones and incretin-based therapy in this group of diabetic patients. The aim of the study is to establish an evidence-based rationale for introducing a GLP-1 analogue to the limited armamentarium of antidiabetic drugs for patients with type T2D and severe renal insufficiency. The overall hypothesis is that patients with T2D and severe renal insufficiency will tolerate and benefit from treatment with the GLP-1 analogue liraglutide, hereby improving glycaemic control and reducing risk factors of cardiovascular disease

Official title: Safety and Effect of Liraglutide in Patients With Type 2 Diabetes and Severe Renal Insufficiency

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Plasma liraglutide concentration (pmol/L)

Secondary outcome:

Hypoglycaemia; minor or major

Glycaemic control

Pancreatic beta-cell function

Cardiovascular risk factors (lipids and blood pressure)

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

Inclusion criteria - patients with T2D in dialysis

- Male or female; aged 18-85 years

- End-stage renal disease

- Chronic dialysis treatment (minimum 3 months)

- T2D (diagnosed according to WHO criteria)

- Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones)

and/or insulin

- Documented beta cell function (evaluated by a glucagon test)

Inclusion criteria - patients with T2D and normal kidney function

- Male or female; aged 18-85 years

- Normal kidney function: Plasma creatinine <0. 105 mmol/L for men and <0. 090 mmol/L for

women

- T2D (diagnosed according to WHO criteria)

- Treated with diet/lifestyle intervention, oral antidiabetic drugs (SU, glitazones)

and/or insulin

- Documented beta cell function (evaluated by a glucagon test)

- Hemoglobin A1c ≥6. 5%

Exclusion Criteria - both groups

- Type 1 diabetes mellitus

- Chronic pancreatitis / previous acute pancreatitis

- Known or suspected hypersensitivity to trial product(s) or related products

- Treatment with oral glucocorticoids, calcineurin inhibitors, dipeptidyl peptidase 4

(DPP4) inhibitors or other drugs, which in the Investigator's opinion could interfere with glucose or lipid metabolism 90 days prior to screening

- Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other

clinically significant disorder which in the investigators' opinion could interfere with the results of the trial

- Inflammatory bowel disease

- Cardiac disease defined as: decompensated heart failure (NYHA class III-IV) and/or

diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months

- Body mass index ≤ 18. 5 kg/m2 or ≥ 50. 0 kg/m2

- Females of childbearing potential who are pregnant, breast-feeding, intend to become

pregnant or are not using adequate contraceptive methods

- Clinical signs of diabetic gastroparesis

- Impaired liver function (transaminases >two times upper reference levels)

- Receipt of any investigational product 90 days prior to this trial

- Known or suspected abuse of alcohol or narcotics

- Screening calcitonin ≥50 ng/l

- Subjects with personal or family history of medullary thyroid carcinoma or a personal

history of multiple endocrine neoplasia type 2

Thomas Idorn, MD, Phone: +45 3545 1098, Email: thomas.idorn@rh.regionh.dk

Department of Internal Medicine H, Hillerød Hospital, Hillerød 3400, Denmark; Recruiting
Pernille M Hansen, MD PhD, Phone: +45 48296338, Email: pemh@noh.regionh.dk
Pernille M Hansen, MD PhD, Principal Investigator

Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet, Copenhagen Ø, Copenhagen 2100, Denmark; Recruiting
Thomas Idorn, MD, Phone: +45 3545 0547, Email: thomas.idorn@rh.regionh.dk
Thomas Idorn, MD, Principal Investigator

Department of Endocrinology PE, Copenhagen University Hospital, Rigshospitalet, Copenhagen Ø, Copenhagen 2100, Denmark; Recruiting
Tonny Jensen, Cons, DMSc, Phone: +45 3545 0547, Email: tonny.jensen@rh.regionh.dk
Tonny Jensen, Cons, DMSc, Principal Investigator

Starting date: September 2011
Last updated: September 18, 2012