Abstract
Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, crossover study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra (clinicaltrials.govNCT03200782; n= 12). Both drugs reduced postprandial insulin release and prevented hypoglycemia (symptomatic events requiring rescue glucose: placebo= 7/12, empagliflozin= 2/12, and anakinra= 2/12, pvallikelihood ratio test (LRT) = 0.013; nadir blood glucose for placebo= 2.4mmol/L, 95% CI2.18-2.62, empagliflozin= 2.69mmol/L, 95% CI 2.31-3.08, and anakinra= 2.99mmol/L, 95% CI 2.43-3.55, pvalLRT= 0.048). Moreover, analysis of monocytes exvivo revealed a hyper-reactive inflammatory state that has features of an exaggerated response to a meal. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after gastric bypass surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.
Published Version
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