Background: Postprandial hypoglycemia (PPH) is a debilitating complication after bariatric surgery, due to an exaggerated hyperinsulinemic response after carbohydrate ingestion. Recent studies have shown that IL-1β contributes to the postprandial stimulation of insulin. Similarly, lowering hyperglycemic peak by SGLT2-inhibition may reduce insulin secretion. We investigated whether the IL-1 receptor antagonist anakinra or empagliflozin influence PPH in patients after gastric bypass.
Methods: We included 12 subjects with PPH after gastric bypass in a placebo controlled, double-blind, randomized, cross-over proof-of-concept study. Subjects received on each of the 3 study days either empagliflozin, anakinra or the respective placebos followed by a mixed-meal-test (MMT) with assessment of hypoglycaemia.
Results: Treatment with empagliflozin reduced 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 of the MMT compared to placebo and was followed by a significant reduction of hypoglycemic events (n = 2, 16.6%) compared to placebo (n = 8, 61.5%). Treatment with anakinra showed a similar glucose curve as placebo, but was also followed by a significantly reduced rate of hypoglycemic events (n = 2, 16.6%). Both treatment interventions showed lowered insulin and c-peptide levels compared to placebo (p<0.001).
Conclusion: Empagliflozin as well as Anakinra significantly reduced hypoglycemic episodes in patients after gastric bypass by decreased insulin secretion. Therefore, empagliflozin and IL-1 antagonism, could be promising novel therapeutic options for patients with refractory PPH after gastric bypass.
M. Hepprich: None. B. Schelker: None. S.J. Wiedemann: None. B. Trinh: None. M. Böni-Schnetzler: None. M.Y. Donath: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Novartis AG, Novo Nordisk A/S, Sanofi.
University of Basel