Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

The GLP-1 receptor agonist lixisenatide reduces postprandial glucose in patients with diabetes secondary to total pancreatectomy: a randomised, placebo-controlled, double-blinded crossover trial

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Major decreases in the lipidome following liraglutide treatment

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

  3. Profiling of gut microbiota and plasma metabolites in persons with type 1 diabetes and kidney disease

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

  4. Pregnancy loss is associated with type 2 diabetes: a nationwide case-control study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Gut Mucosal Gene Expression and Metabolic Changes After Roux-en-Y Gastric Bypass Surgery

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Nonalcoholic Fatty Liver Disease Impairs the Liver-Alpha Cell Axis Independent of Hepatic Inflammation and Fibrosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

AIMS/HYPOTHESIS: Treatment of diabetes secondary to total pancreatectomy remains a challenge and insulin constitutes the only glucose-lowering treatment for these patients. We hypothesised that the glucagon-like peptide 1 (GLP-1) receptor agonist lixisenatide would improve postprandial glucose tolerance in totally pancreatectomised patients.

METHODS: In a double-blinded, randomised, crossover study, 12 totally pancreatectomised individuals (age: 65.0 ± 9.5 mean±SD years; BMI: 22.9 ± 3.9 kg/m2) and 12 healthy control individuals (age 66.1 ± 7.6 years; BMI: 24.0 ± 2.9 kg/m2) underwent two 3 h liquid mixed-meal tests (with paracetamol for assessment of gastric emptying) after single-dose injection of 20 μg of lixisenatide or placebo. Basal insulin was given the night before each experimental day; no insulin was given during study days.

RESULTS: Compared with placebo, lixisenatide reduced postprandial plasma glucose excursions in the pancreatectomy group (baseline-subtracted AUC [bsAUC] [mean±SEM]: 548 ± 125 vs 1447 ± 95 mmol/l × min, p < 0.001) and in the control group (-126 ± 12 vs 222 ± 51 mmol/l × min, p < 0.001). In the pancreatectomy group a mean peak glucose concentration of 23.3 ± 1.0 mmol/l was reached at time point 134 ± 11 min with placebo, compared with a mean peak glucose concentration of 18 ± 1.4 mmol/l (p = 0.008) at time point 148 ± 13 min (p = 0.375) with lixisenatide. In the control group a mean peak concentration of 8.2 ± 0.4 mmol/l was reached at time point 70 ± 13 min with placebo, compared with a mean peak concentration of 5.5 ± 0.1 mmol/l (p < 0.001) at time point 8 ± 25 min (p = 0.054) with lixisenatide. Lixisenatide also reduced gastric emptying and postprandial glucagon responses in the pancreatectomy group (66 ± 84 vs 1190 ± 311 pmol/l × min, p = 0.008) and in the control group (141 ± 100 vs 190 ± 100 pmol/l × min, p = 0.034). In the pancreatectomy group, C-peptide was undetectable in plasma. In the control group, postprandial plasma C-peptide responses were reduced with lixisenatide (18 ± 17 vs 189 ± 31 nmol/l × min, p < 0.001).

CONCLUSIONS/INTERPRETATION: The GLP-1 receptor agonist lixisenatide reduces postprandial plasma glucose excursions in totally pancreatectomised patients. The mode of action seems to involve deceleration of gastric emptying and reduced postprandial responses of gut-derived glucagon.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02640118.

FUNDING: This study was funded by an unrestricted investigator-initiated study grant from Sanofi. Support was also received from from the Novo Nordisk Foundation Center for Basic Metabolic Research, the A.P. Møller Foundation for the Advancement of Medical Science and the Faculty of Health and Medical Sciences, University of Copenhagen.

OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind63
Udgave nummer7
Sider (fra-til)1285-1298
Antal sider14
ISSN0012-186X
DOI
StatusUdgivet - jul. 2020

ID: 59837764