End-stage Renal Disease, Type 2 Diabetes Mellitus
Conditions
Keywords
Liraglutide, Uremia, Dialysis, Type 2 diabetes mellitus, Safety, Efficacy
Brief summary
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
Interventions
DRUGLiraglutide
Daily sc. injection, individual dosage
Sponsors
Novo Nordisk A/S
The GCP unit at Copenhagen University Hospital
Bo Feldt-Rasmussen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma liraglutide concentration (pmol/L) | 12 weeks | Plasma liraglutide concentration evaluated over time during continuous intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycaemia; minor or major | 12 weeks | Number of hypoglycaemic episodes during intervention. Minor (blood glucose \<3.1 mmol/L, no need for assistance). Major (blood glucose \<3.1 mmol/L, assistance from third person required) |
| Glycaemic control | 12 weeka | Glycaemic control evaluated from 3 daily measurements of blood glucose, from 4 periods of 24-hour tissue glucose measurements (5 days each) and from HbA1c during the intervention period. |
| Pancreatic beta-cell function | 12 weeks | Pancreatic beta-cell function evaluated from insulin- and C-peptide-secretion during a standard meal test 3 times during the intervention period. |
| Cardiovascular risk factors (lipids and blood pressure) | 12 weeks | Blood pressure will be evaluated at each visit and lipid profile (HDL, LDL, total cholesterol and triglyceride) 3 times during the intervention period. |
Countries
Denmark
Outcome results
None listed