Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial
Authors: Christopher K Rayner
Andrea Natali
Silvia Frascerra
Michael Horowitz
Kylie Lange
Michelle J Bound
Tongzhi Wu
Domenico Tricò
Linda E Watson
Karen L Jones
Liza K Phillips
Andrea Mari
Ele Ferrannini
Jacqueline Grivell
Journal: Diabetes Care (2020)
Discipline: CLINICAL MEDICINE
Keywords: Tachyphylaxis; Gastric emptying; GLP-1 receptor agonist; Lixisenatide; Postprandial glycemia
Affiliations: Centre of Research Excellence for Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, Australia ., 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., 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.

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 &lt; 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P &lt; 0.001) and incremental AUC for blood glucose (P &lt; 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. 

Retracted: No

PubPeer comments:
 The authors proposed in this paper a new notion of u201c**hesitant triangular fuzzy sets**u201d and various types of aggregation operators for multiple attribute decision making. However, these operators are not justified and are merely symbol manipulation. For example, (a) The description in Definition 9 u201ca hesitant triangular fuzzy set (HTFS) on $X$ is in terms of a function that when applied to each $x$ in $X$ and returns a subset of values in [0, 1].u201d does not match eq.(7). (b) The operator in Definition 12 is not well defined because the involved hesitant triangular fuzzy elements may not be well ranked according to the order relation introduced in Definition 10. See also https: pubpeer.com publications 9C9795A6774F0774927DE80DA57B8A ![file] ![file] ![file] , 
 A typical citation pattern of GW Wei, the first author of this paper. ![file] ![file] ![file] ![file] ,