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.2025-07-142025-07-142020Diabetes Care, 2020; 43(8):1813-18211935-55481935-5548https://hdl.handle.net/2440/145900Corrected by: Erratum: The formula for the calculation of the glucose management indicator (GMI) was incorrect as written in the above-referenced article. The sentence “GMI percentage was calculated as (3.31 + 0.02392) × mean glucose in mg/dL” is changed to read as follows: “GMI percentage was calculated as 3.31 + (0.02392 × mean glucose in mg/dL).”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: Atotal of 30 patients withmetformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) aftera75-g glucosedrink,beforeandafter8weeks’ treatmentwithlixisenatide(20mg 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 5 0.003) and insulin (P 5 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 (r520.74, P50.002) and to the baseline rate of emptying (r50.52, P 5 0.048) but unrelated to b-cell function (assessed by b-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.en© 2020 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.Tachyphylaxis; glucagon-like peptide 1 (GLP-1); GLP-1 receptor agonist; lixisenatide; gastric emptying; postprandial glycemiaHumansDiabetes Mellitus, Type 2GlucagonInsulinBlood GlucosePeptidesPlacebosHypoglycemic AgentsDrug Administration ScheduleDouble-Blind MethodGastric EmptyingPostprandial PeriodTime FactorsAgedMiddle AgedAustraliaFemaleMaleJournal article10.2337/dc20-01902024-05-06533623Rayner, C.K. [0000-0002-5527-256X]Phillips, L.K. [0000-0002-9066-717X]Lange, K. [0000-0003-3814-8513]Bound, M.J. [0000-0003-0211-5832]Wu, T. [0000-0003-1656-9210]Jones, K.L. [0000-0002-1155-5816]Horowitz, M. [0000-0002-0942-0306]