The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects
- Conditions
- Diabetes After Total Pancreatectomy
- Interventions
- Registration Number
- NCT02640118
- Lead Sponsor
- University Hospital, Gentofte, Copenhagen
- Brief Summary
Postprandial glucose (PPG) excursions are not only determined by insulin-mediated glucose disposal and endogenous glucose production (regulated by insulin and glucagon); also the rate of gastric emptying constitutes an important determinant of PPG levels 1. The short-acting glucagon-like peptide-1 (GLP-1) receptor agonist lixisenatide is used in the treatment of type 2 diabetes. It increases glucose-dependent insulin secretion, suppresses glucagon secretion and reduces gastric emptying of meals 2. These three mechanisms most likely constitute the weightiest mechanisms behind the potent impact of lixisenatide on exaggerated PPG excursions in patients with type 2 diabetes - which often are normalised during lixisenatide treatment 3. However, the separate impact of lixisenatide-induced reduction of gastric emptying (independently of the pancreatic effects) has been difficult to determine. Importantly, treatment with lixisenatide also decreases appetite and food intake and may, like native GLP-1, increase energy expenditure 4. So far an exact demarcation of the pancreatic and extrapancreatic effects of lixisenatide in humans remains to be established.
The present project serves to determine whether effects of lixisenatide on gastric emptying, appetite, food intake and resting energy expenditure are dependent on the endocrine pancreas.
The study is a randomised, placebo-controlled, double-blinded, cross-over study.
12 healthy persons and 12 pancreatectomized patients (i.e. patients who have had their pancreata removed due to pancreatic cancer or severe chronic pancreatitis) will be subjected to two experimental days on which they will undergo a liquid meal test followed by a fasting period and finished off with an ad libitum meal with lixisenatide and placebo, respectively.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Pancreatectomised + Lixisenatide Standardized liquid meal During the experimental day the patient will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a Lixisenatide-injection will be given subcutaneously Pancreatectomized + lixisenatide-placebo Standardized liquid meal During the experimental day the patient will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a placebo-injection will be given subcutaneously. Healthy + lixisenatide-placebo Standardized liquid meal During the experimental day the subject will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a placebo-injection will be given subcutaneously Pancreatectomized + lixisenatide-placebo Lixisenatide-Placebo During the experimental day the patient will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a placebo-injection will be given subcutaneously. Healthy + lixisenatide-placebo Lixisenatide-Placebo During the experimental day the subject will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a placebo-injection will be given subcutaneously Healthy + Lixisenatide Standardized liquid meal During the experimental day the subject will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a Lixisenatide-injection will be given subcutaneously Pancreatectomised + Lixisenatide Lixisenatide During the experimental day the patient will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a Lixisenatide-injection will be given subcutaneously Healthy + Lixisenatide Lixisenatide During the experimental day the subject will ingest a standardized liquid meal (200 ml containing 1,650 kJ (394 kcal): carbohydrate 50%, protein 15%, fat 35%, consisting of glucose (48.4 g + 1.6 g \[U-13C6\]-glucose), rapeseed oil (14.1 g), whey protein (15.2 g) and 1.5 g paracetamol). Before the meal a Lixisenatide-injection will be given subcutaneously
- Primary Outcome Measures
Name Time Method PPG excursions measured as incremental area under curve (iAUC) -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes
- Secondary Outcome Measures
Name Time Method differences in gastric emptying, measurement of s-paracetamol -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes measurement of time to peak and incremental area under the curve (iAUC)
resting energy expenditure (REE) -90,30,150 minutes measured by calorimetry
glucagon, gastrin, cholecystokinin, GIP, GLP-1, oxyntomodulin -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes food intake and appetite at time 0,30,60,90,120,150,180 minutes assessed by a visual analogue scale (VAS)
p-C-peptide pmol/l -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes p-glucose mmol/L -30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes