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.
18 - 21 May 2019
European Society of Endocrinology