PMID- 35460043 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221014 IS - 1869-6953 (Print) IS - 1869-6961 (Electronic) IS - 1869-6961 (Linking) VI - 13 IP - 6 DP - 2022 Jun TI - Acute Administration of the GLP-1 Receptor Agonist Lixisenatide Diminishes Postprandial Insulin Secretion in Healthy Subjects But Not in Type 2 Diabetes, Associated with Slowing of Gastric Emptying. PG - 1245-1249 LID - 10.1007/s13300-022-01258-4 [doi] AB - INTRODUCTION: It is uncertain whether lixisenatide has postprandial insulinotropic effects when its effect on slowing gastric emptying is considered, in healthy subjects and type 2 diabetes mellitus (T2DM). We evaluated the effects of single administration of 10 mug sc lixisenatide on glycaemia, insulin secretion and gastric emptying (GE), measured using the 'gold standard' technique of scintigraphy following an oral glucose load (75 g glucose). METHODS: Fifteen healthy subjects (nine men, six women; age 67.2 +/- 2.3 years) and 15 patients with T2DM (nine men, six women; age 61.9 +/- 2.3 years) had measurements of GE, plasma glucose, insulin and C-peptide for 180 min after a radiolabeled 75 g glucose drink on two separate days. All subjects received lixisenatide (10 mug sc) or placebo in a randomised, double-blind, crossover fashion 30 min before the drink. Insulin secretory response (ISR) was determined using the C-peptide deconvolution method. RESULTS: GE was markedly slowed by lixisenatide compared with placebo in both healthy subjects (1.45 +/- 0.10 kcal/min for placebo vs. 0.60 +/- 0.14 kcal/min for lixisenatide) and diabetes (1.57 +/- 0.06 kcal/min for placebo vs. 0.75 +/- 0.13 kcal/min for lixisenatide) (both P < 0.001) with no difference between the two groups (P = 0.42). There was a moderate to strong inverse correlation between the early insulin secretory response calculated at 60 min and gastric retention at 60 min with lixisenatide treatment in healthy subjects (r = - 0.8, P = 0.0003) and a trend in type 2 diabetes (r = - 0.4, P = NS), compared with no relationships in the placebo arms (r = - 0.02, P = NS, healthy subjects) and (r = - 0.16, P = NS, type 2 diabetes). CONCLUSION: The marked slowing of GE of glucose induced by lixisenatide is associated with attenuation in the rise of postprandial glucose in both healthy subjects and diabetes and early insulin secretory response in healthy subjects. CLINICAL TRIALS REGISTRATION NUMBER: NCT02308254. CI - (c) 2022. The Author(s). FAU - Marathe, Chinmay S AU - Marathe CS AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. FAU - Pham, Hung AU - Pham H AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. FAU - Wu, Tongzhi AU - Wu T AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. FAU - Trahair, Laurence G AU - Trahair LG AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. FAU - Rigda, Rachael S AU - Rigda RS AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. FAU - Buttfield, Madeline D M AU - Buttfield MDM AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. FAU - Hatzinikolas, Seva AU - Hatzinikolas S AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. FAU - Lange, Kylie AU - Lange K AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. FAU - Rayner, Christopher K AU - Rayner CK AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. AD - Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia. FAU - Mari, Andrea AU - Mari A AD - CNR Institute of Clinical Physiology, Pisa, Italy. FAU - Horowitz, Michael AU - Horowitz M AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. FAU - Jones, Karen L AU - Jones KL AUID- ORCID: 0000-0002-1155-5816 AD - Adelaide Medical School, Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide Health and Medical Sciences Building, Cnr North Tce and George St, Adelaide, SA, 5005, Australia. karen.jones@adelaide.edu.au. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. karen.jones@adelaide.edu.au. LA - eng SI - ClinicalTrials.gov/NCT02308254 PT - Journal Article DEP - 20220422 PL - United States TA - Diabetes Ther JT - Diabetes therapy : research, treatment and education of diabetes and related disorders JID - 101539025 PMC - PMC9174387 OTO - NOTNLM OT - Gastric emptying OT - Insulin secretion OT - Lixisenatide OT - Postprandial glycaemia OT - Type 2 diabetes EDAT- 2022/04/24 06:00 MHDA- 2022/04/24 06:01 PMCR- 2022/04/22 CRDT- 2022/04/23 05:25 PHST- 2022/02/01 00:00 [received] PHST- 2022/03/21 00:00 [accepted] PHST- 2022/04/24 06:00 [pubmed] PHST- 2022/04/24 06:01 [medline] PHST- 2022/04/23 05:25 [entrez] PHST- 2022/04/22 00:00 [pmc-release] AID - 10.1007/s13300-022-01258-4 [pii] AID - 1258 [pii] AID - 10.1007/s13300-022-01258-4 [doi] PST - ppublish SO - Diabetes Ther. 2022 Jun;13(6):1245-1249. doi: 10.1007/s13300-022-01258-4. Epub 2022 Apr 22.