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Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

ABSTRACT: Postprandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among patients with recurrent hypoglycemia. These patients also have increased postprandial levels of insulin and glucagon-like peptide 1 (GLP-1). We performed a clinical trial to determine the role of GLP-1 in postprandial glycemia in patients with hyperinsulinemic hypoglycemia syndrome after gastric bypass.Nine patients with recurrent hypoglycemia after gastric bypass (H-GB), 7 patients who were asymptomatic after gastric bypass (A-GB), and 8 healthy control subjects underwent a mixed-meal tolerance test (350 kcal) using a dual glucose tracer method on 2 separate days. On 1 day they received continuous infusion of the GLP-1 receptor antagonist exendin (9-39) (Ex-9), and on the other day they received a saline control. Glucose kinetics and islet and gut hormone responses were measured before and after the meal.Infusion of Ex-9 corrected hypoglycemia in all patients with H-GB. The reduction in postprandial insulin secretion by Ex-9 was greater in the H-GB group than in the other groups (H-GB, 50% ± 8%; A-GB, 13% ± 10%; controls, 14% ± 10%) (P < .05). The meal-derived glucose appearance was significantly greater in subjects who had undergone gastric bypass compared to the controls and in the H-GB group compared to the A-GB group. Ex-9 shortened the time to reach peak meal-derived glucose appearance in all groups without a significant effect on overall glucose flux. Postprandial glucagon levels were higher among patients who had undergone gastric bypass than controls and increased with administration of Ex-9.Hypoglycemia after gastric bypass can be corrected by administration of a GLP-1 receptor antagonist, which might be used to treat this disorder. These findings are consistent with reports that increased GLP-1 activity contributes to hypoglycemia after gastric bypass. ClinicalTrials.gov, Number: NCT01803451.

SUBMITTER: Salehi M

PROVIDER: S-EPMC3943944 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

Salehi Marzieh M Gastaldelli Amalia A D'Alessio David A DA

Gastroenterology 20131204 3

<h4>Background & aims</h4>Postprandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among patients with recurrent hypoglycemia. These patients also have increased postprandial levels of insulin and glucagon-like peptide 1 (GLP-1). We performed a clinical trial to determine the role of GLP-1 in postprandial glycemia in patients with hyperinsulinemic hypoglycemia syndrome after gastric bypass.<h4>Methods</h4>Nine patients with recurrent hypoglycemia after ...[more]

PMID: 24315990

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Project description:BackgroundRecent evidence has emerged concerning hypoglycemia following the application of glucagon-like peptide-1 receptor agonists (GLP-1RAs). Nevertheless, few real-world investigations have been performed to determine the clinical characteristics, onset, and outcomes of hypoglycemia associated with different GLP-1RAs. This study aimed to compare and assess the relationship between various GLP-1RAs and hypoglycemia in a large population based on updated data from the Food and Drug Administration Adverse Event Reporting System (FAERS).MethodsBayesian and disproportionality analyses were applied to data mining in order to investigate suspected cases of hypoglycemia following various GLP-1RAs using the FAERS data between January 2004 and September 2020. We also evaluated the onset time, fatality risks, and hospitalization proportions of GLP-1RA-related hypoglycemia.ResultsWe identified 1,164 GLP-1RA-associated hypoglycemia cases, which seemed to affect more middle-aged patients than elderly ones. Also, females were more affected than males. Lixisenatide demonstrated a stronger association with hypoglycemia compared to other GLP-1RAs, according to the highest reporting odds ratio (ROR) (28.03, 95% confidence interval =15.92, 49.32), empirical Bayes geometric mean [26.00, 95% confidence interval (CI): 16.20], and proportional reporting ratio (PRR) (26.01, χ2=313.37). The median time to hypoglycemia onset was 5 days (interquartile range, 0-67.75 days) following GLP-1RA treatment. In general, GLP-1RA-associated hypoglycemia resulted in fatality and hospitalization proportions of 3.53% and 56.08%, respectively.ConclusionsBy analyzing the FAERS data, we outlined the association between hypoglycemia and different GLP-1RAs in greater detail in terms of clinical features, onset, and outcomes. Among all six GLP-1RAs, lixisenatide demonstrated the strongest association with hypoglycemia while no relationship between albiglutide and hypoglycemia was observed. Attention should be given to GLP-1RAs when used in patients with high risks of hypoglycemia.

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Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

Publications

Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

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