ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP137 | DOI: 10.1530/endoabs.63.GP137

Empagliflozin as well as Anakinra reduce symptomatic hypoglycemia in patients after Roux-Y-gastric bypass by lowered insulin secretion

Matthias Hepprich1, Sophia Wiedemann1, Benjamin Schelker1, Alessandra Stärkle2, Beckey Trinh1, Marianne Böni-Schnetzler1, Gottfried Rudofsky3 & Marc Donath1

1Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland; 2Swiss Federal Institute of Technology Zurich, Department of Health Sciences and Technology, Zurich, Switzerland; 3Endocrinology and Metabolic Diseases, Cantonal Hospital Olten, Olten, Switzerland.

Background: Postprandial hypoglycemia is an increasingly recognized complication after bariatric surgery. Its hallmark is a pronounced glycemic rise after carbohydrate ingestion followed by an exaggerated hyperinsulinemic response. Recent studies have shown that IL-1β contributes to postprandial stimulation of insulin. Furthermore, inhibition of SGLT2 reduces excessive plasma glucose increase. Therefore, we investigated whether inhibition of IL-1β with the IL-1 receptor antagonist anakinra or inhibition of SGLT2 with empagliflozin may reduce postprandial hypoglycemia.

Methods: We performed a placebo controlled, double-blind, randomized, cross-over proof-of-concept study with 12 subjects with confirmed postprandial hypoglycemia after gastric bypass. Subjects received on each of the 3 study days either empagliflozin p. o. or anakinra s. c. along with the respective placebos followed by a standardized liquid mixed-meal-test over three hours with regular clinical assessments and measurement for glucose, insulin, c-peptide, GLP1, glucagon and inflammatory parameters.

Results: Compared to placebo, 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 and was followed by a significant reduction of glucose-requiring hypoglycemic events (n=2, 16.6% vs. n=8, 61.5%, p-value 0.041). Similarly, treatment with anakinra also reduced the rate of glucose-requiring hypoglycemic events (n=2, 16.6%) compared to placebo (n=8, 61.5%). Anakinra (AUC 63,458) and empagliflozin (AUC 55,116,) significantly lowered insulin secretion compared to placebo (AUC 80,029). Glucagon and GLP1 levels remained unchanged.

Conclusion: Empagliflozin and anakinra prevented glucose-requiring hypoglycemic episodes in patients after Roux-Y-gastric bypass by decreased insulin secretion via two different mechanisms. Empagliflozin by preventing an excessive postprandial rise in glycemic rise and anakinra may exert direct inhibitory effects on insulin secretion.