Autor:innen:
Dr. Matthias Hepprich | Universitätsspital Basel | Switzerland
Benjamin Schelker | Universitätsspital Basel | Switzerland
Alessandra Staerkle | Swiss Federal Institute of Technology Zurich, Zurich, Switzerland | Switzerland
Dr. Beckey Trinh | Universitätsspital Basel | Switzerland
Sophia Wiedemann | Universitätsspital Basel | Switzerland
PD Dr. Marianne Böni-Schnetzler | Universitätsspital Basel | Switzerland
Prof. Dr. Gottfried Rudofsky | Kantonsspital Olten | Switzerland
Prof. Dr. Marc Donath | Universitätsspital Basel | Switzerland
Background: Postprandial hypoglycemia after bariatric surgery is characterized by a pronounced glycemic rise after carbohydrate ingestion and an exaggerated hyperinsulinemic response(1). Recent studies have shown that IL-1β contributes to the postprandial stimulation of insulin(1), and that bariatric surgery affects the gut flora and associated inflammatory response. Furthermore, inhibition of the SGLT2 may reduce excessive plasma glucose increase. Therefore, we investigated whether inhibition of IL-1β with the IL-1 receptor antagonist anakinra and/or inhibition of SGLT2 with empagliflozin reduces postprandial hypoglycemia after bariatric surgery.
Methods: In this placebo controlled, double-blind, randomized, cross-over proof-of-concept study 12 subjects with confirmed postprandial hypoglycemia after gastric bypass were included. Subjects received on each of the 3 study days either empagliflozin p. o. or anakinra s. c. along with the respective placebo or double placebos. Three hours after injection (anakinra or placebo) and two hours after ingestion of the oral study medication (empagliflozin or placebo) a mixed-meal-test was performed with assessment of hypoglycemia. Clinical assessments (Edinburgh hypoglycemia scale, mini mental status test, Sigstad score, Stanford sleepiness Scale) were performed aside measurement for glucose, insulin, c-peptide as well as inflammatory parameters.
Results: Empagliflozin reduced peak glycaemia at 30 (11.2 vs. 10.1 mmol/l), 60 (9.1 vs. 6.9 mmol/l) and 90 (4.5 vs. 3.5 mmol/l) minutes after ingestion of the mixed meal compared to placebo and was followed by a significant reduction of glucose-requiring hypoglycemic events (n = 2, 16.6 %) compared to placebo (n = 8, 61.5 %). In contrast, treatment with Anakinra did not result in significant changes of the glucose curve within the first 90 minutes, but was also followed by a significantly reduced rate of glucose-requiring hypoglycemic events (n = 2, 16.6 %) compared to placebo (n = 8, 61.5 %). Both treatment interventions showed significantly lowered insulin secretion compared to placebo.
Conclusion: Empagliflozin as well as Anakinra lowered glucose-requiring hypoglycemic episodes in patients after Roux-Y-gastric bypass by decreased insulin secretion. Therefore, empagliflozin may be a promising novel therapeutic option for patients with refractory postprandial hypoglycemia.