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Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial.
Diabetes Care. 2020 Aug; 43(8):1813-1821.DC

Abstract

OBJECTIVE

Tachyphylaxis for slowing of gastric emptying is seen with continuous exposure to glucagon-like peptide 1 (GLP-1). We therefore aimed to establish whether prolonged use of a "short-acting" GLP-1 receptor agonist, lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia.

RESEARCH DESIGN AND METHODS

A total of 30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75-g glucose drink, before and after 8 weeks' treatment with lixisenatide (20 μg subcutaneously daily) or placebo, in a double-blind randomized parallel design.

RESULTS

Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under the curve [AUC] over 240 min of 2.19 [95% CI 1.82, 2.64], P < 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P < 0.001) and incremental AUC for blood glucose (P < 0.001). Lixisenatide suppressed both glucagon (P = 0.003) and insulin (P = 0.032), but not endogenous glucose production, over 120 min after oral glucose intake. Postprandial glucose lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = -0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048) but unrelated to β-cell function (assessed by β-cell glucose sensitivity).

CONCLUSIONS

Eight weeks' treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1 receptor agonists therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.

Authors+Show Affiliations

Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia chris.rayner@adelaide.edu.au. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.CNR Institute of Clinical Physiology, Pisa, Italy.Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.CNR Institute of Neuroscience, Padua, Italy.Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32471908

Citation

Rayner, Christopher K., et al. "Effects of Sustained Treatment With Lixisenatide On Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: a Randomized Controlled Trial." Diabetes Care, vol. 43, no. 8, 2020, pp. 1813-1821.
Rayner CK, Watson LE, Phillips LK, et al. Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Care. 2020;43(8):1813-1821.
Rayner, C. K., Watson, L. E., Phillips, L. K., Lange, K., Bound, M. J., Grivell, J., Wu, T., Jones, K. L., Horowitz, M., Ferrannini, E., Tricò, D., Frascerra, S., Mari, A., & Natali, A. (2020). Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Care, 43(8), 1813-1821. https://doi.org/10.2337/dc20-0190
Rayner CK, et al. Effects of Sustained Treatment With Lixisenatide On Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: a Randomized Controlled Trial. Diabetes Care. 2020;43(8):1813-1821. PubMed PMID: 32471908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial. AU - Rayner,Christopher K, AU - Watson,Linda E, AU - Phillips,Liza K, AU - Lange,Kylie, AU - Bound,Michelle J, AU - Grivell,Jacqueline, AU - Wu,Tongzhi, AU - Jones,Karen L, AU - Horowitz,Michael, AU - Ferrannini,Ele, AU - Tricò,Domenico, AU - Frascerra,Silvia, AU - Mari,Andrea, AU - Natali,Andrea, Y1 - 2020/05/29/ PY - 2020/01/27/received PY - 2020/04/28/accepted PY - 2020/5/31/pubmed PY - 2020/5/31/medline PY - 2020/5/31/entrez SP - 1813 EP - 1821 JF - Diabetes care JO - Diabetes Care VL - 43 IS - 8 N2 - OBJECTIVE: Tachyphylaxis for slowing of gastric emptying is seen with continuous exposure to glucagon-like peptide 1 (GLP-1). We therefore aimed to establish whether prolonged use of a "short-acting" GLP-1 receptor agonist, lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. RESEARCH DESIGN AND METHODS: A total of 30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75-g glucose drink, before and after 8 weeks' treatment with lixisenatide (20 μg subcutaneously daily) or placebo, in a double-blind randomized parallel design. RESULTS: Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under the curve [AUC] over 240 min of 2.19 [95% CI 1.82, 2.64], P < 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P < 0.001) and incremental AUC for blood glucose (P < 0.001). Lixisenatide suppressed both glucagon (P = 0.003) and insulin (P = 0.032), but not endogenous glucose production, over 120 min after oral glucose intake. Postprandial glucose lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = -0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048) but unrelated to β-cell function (assessed by β-cell glucose sensitivity). CONCLUSIONS: Eight weeks' treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1 receptor agonists therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/32471908/Effects_of_Sustained_Treatment_With_Lixisenatide_on_Gastric_Emptying_and_Postprandial_Glucose_Metabolism_in_Type_2_Diabetes:_A_Randomized_Controlled_Trial L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=32471908 DB - PRIME DP - Unbound Medicine ER -
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