None listed
Conditions
Brief summary
When we ingest a meal a number of hormones, including glucagon-like peptide-1 (GLP-1), are released from the small intestine. These hormones play an important role in regulating the motor function of the gut, blood pressure, the levels of sugar and fat in the blood, and the rate at which the body uses energy. The effect of these hormones is, however, limited by the fact that they undergo rapid degradation by an enzyme in the blood. There is a new class of type 2 diabetic drugs that act by inhibiting this enzyme, and as a result, these drugs improve blood glucose levels. We have recently shown that these drugs (e.g. vildagliptin) also enhance metabolic rate (an effect that may prevent weight gain) and decrease levels of triglycerides in the blood in healthy volunteers. This study aims to determine if these drugs have the same effects during fat infusion in patients with type 2 diabetes, and to determine the specific role of the gut hormone, glucagon-like peptide-1 (GLP-1) in mediating these responses.
Interventions
Arm 1: Galvus (vildagliptin) 50 mg (oral, single dose only) + intravenous infusion of 0.9% saline (for 210 minutes)
Arm 2: Placebo (oral, single dose only) + intravenous infusion of 0.9% saline (for 210 minutes)
Arm 3: Galvus (50 mg) (oral, single dose only) + exendin(9-39) (a glucagon-like peptide-1 (GLP-1) receptor antagonist, administered at a dose of 900 pmol/kg/min for 210 min)
Adherance will be monitored by the investigators who will administer the drugs in the laboratory. Plasma concentr
Arm 1: Galvus (vildagliptin) 50 mg (oral, single dose only) + intravenous infusion of 0.9% saline (for 210 minutes) Arm 2: Placebo (oral, single dose only) + intravenous infusion of 0.9% saline (for 210 minutes) Arm 3: Galvus (50 mg) (oral, single dose only) + exendin(9-39) (a glucagon-like peptide-1 (GLP-1) receptor antagonist, administered at a dose of 900 pmol/kg/min for 210 min) Adherance will be monitored by the investigators who will administer the drugs in the laboratory. Plasma concentrations of GLP-1 will determine drug efficacy. This is a cross-over study, each visit will be separated by at least 7 days. On each day, participants will receive an intraduodenal infusion of fat (Intralipid, 2 kcal/min for 120 min, administered 60 min after ingestion of vildagliptin/placebo and commencement of i.v. infusion of exendin9-39/saline).
Sponsors
Dr Tanya Little
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
- Patients with type 2 diabetes managed by diet alone or Metformin - glycated haemoglobin (HbA1c) greater than or equal to 6.0% and less than or equal to 7.9% - body mass index of 25-35 kg/m2 - aged between 40-75 years - Males and post-menopausal females (to control for the effect of the menstrual cycle on gut hormone secretion) - Haemoglobin above the lower limit of the normal range (i.e. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. >10mcg/L)
Exclusion criteria
- use of oral hypoglycaemic drugs other than Metformin or insulin - significant gastrointestinal symptoms; disease or surgery - current use of any prescribed or non-prescribed medications, that may affect gastrointestinal function within 48 hours of the study (e.g. domperidone and cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St John's Wort) - epilepsy - coronary heart disease, heart attack or failure, stroke or respiratory disease (COPD, cystic fibrosis) - any other significant illness as assessed by the investigator - intake of > 20 g alcohol on a daily basis - smokers (cigarettes, cigars, marijuana) - donation of blood (either through Red Cross or research activities) in the 12 weeks prior to enrolment in the study. Participants will also be instructed to abstain from donating blood for 12 weeks after study completion. A screening blood sample will be taken to ensure that only individuals with normal haemoglobin and iron levels are included in the study. - consumption of a vegetarian diet - inability to comprehend study protocol - known lactose intolerance, intolerance, allergy to vildagliptin - liver function tests and creatinine clearance outside the following ranges Alanine aminotransferase (ALT) 0 -55 U/l Alkaline phosphatase 30 - 110 U/l Aspartate transaminase 0 - 45 U/l Bilirubin 6 - 24 mmol/l Calculated creatinine clearance will be determined as follows: Cr clearance = [140 - age (years) x weight (kg)] / serum creatinine (micro mol/L) Creatinine clearance cut-off of <50 ml/min AND/OR serum creatinine concentration >0.12mmol/l will be excluded.
Outcome results
None listed