Conditions: Hyperlipidemia
Keywords: Intestinal lipoprotein Apolipoprotein B48 and apolipoprotein B100 Pancreatic clamp DPPIV inhibitor
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 21
Healthy volunteers: yes

Brief summary:
Recent studies in both animals and humans has demonstrated that the hormone GLP-1 (glucagon like peptide 1) reduces intestinal production of lipoprotein particles. The investigators therefore hypothesise that the drug sitagliptin which prevents the breakdown of GLP-1 will reduce intestinal lipoprotein production in humans. The investigators are unable to speculate whether sitagliptin will affect hepatic lipoprotein production because of lack of of data from animal studies or in vitro data. Sitagliptin is already an approved treatment for type 2 diabetes.

Detailed description:
Each subject will be studied twice 4-6 weeks apart in random order in this single blinded study. In study A they will receive a single dose of sitagliptin 100mg od. In study B they will receive placebo. A nasoduodenal tube will be sited under fluoroscopic guidance the day prior to the study. On the day of the study regular liquid formula (Great shake plus) will be infused from 4am through the tube to maintain a constant fed state. A pancreatic clamp (octreotide with replacement glucose, insulin and growth hormone) along with saline/sitagliptin will be started at 7am. From 9am an iv bolus of deuterated-glycerol (d5-glycerol) along with a regular infusion of deuterated leucine (L-\[5,5,5-2H3\]. Regular blood samples will be drawn to assess lipoprotein kinetics.

Arms:
arm 1: sitagliptin, 100mg, oral, single dose arm 2: Placebo, oral, single dose

Interventions: intervention 1: Sitagliptin intervention 2: Placebo
Intervention descriptions: intervention 1: Sitagliptin, 100mg, oral, single dose intervention 2: Placebo, oral, single dose

Protocol document: