CompletedNot Applicable

The Impact of Lixisenatide on Postprandial Glucose Tolerance in Pancreatectomised Subjects

24 participantsStarted 2015-08

Plain-language 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.

Who can participate

Age range18 Years – 80 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria Pancreatectomised patients * Caucasians above 18 years of age who have undergone total pancreatectomy * Normal haemoglobin * Informed consent Healthy subjects * Normal fasting plasma glucose (FPG) and normal HbA1C (according to the World Health Organization (WHO) criteria) * Normal haemoglobin * Age above 18 years * Informed consent Exclusion criteria Pancreatectomised patients * Inflammatory bowel disease * Operation within the last 3 months * Ongoing chemotherapy or chemotherapy within the last 3 months * Ostomy * Nephropathy (serum creatinine \>150 µM and/or albuminuria) * Severe liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>3×normal values) * Pregnancy and/or breastfeeding * Age above 80 years * Any condition that the investigator feels would interfere with trial participation Healthy subjects * Diabetes mellitus (DM) * Prediabetes (impaired glucose tolerance and/or impaired FPG) * First degree relatives with DM * Inflammatory bowel disease * Intestinal resection and/or ostomy * Nephropathy (serum creatinine \>150 µM and/or albuminuria * Liver disease (ALAT and/or serum ASAT \>2×normal values) * Pregnancy and/or breastfeeding * Age above 80 years * Any condition that the investigator feels would interfere with trial participation

What they're measuring

PPG excursions measured as incremental area under curve (iAUC)

Timeframe: -120,-45,-30,-15,0,5,10,15,20,25,30,40,50,60,70,80,90,105,120,135,150,180 minutes

Trial details

NCT IDNCT02640118

SponsorUniversity Hospital, Gentofte, Copenhagen

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2016-07