Sacubitril/Valsartan-Induced Hypoglycemia After Gastric Bypass: A Case Report with Documented Endogenous Hyperinsulinemia

Post-bariatric hypoglycemia (PBH) is a frequent yet complex complication following Roux-en-Y gastric bypass, typically related to exaggerated insulin responses after rapid glucose absorption. Identifying alternative or contributing mechanisms is particularly challenging in this population due to altered anatomy and limited access to standard diagnostic tools. We describe the case of a 65-year-old man with a history of type 2 diabetes, obesity, and cardiac sarcoidosis, who achieved diabetes remission after gastric bypass. Several months later, he developed frequent postprandial and nocturnal hypoglycemic episodes despite strict dietary adjustments. Continuous glucose monitoring showed 38% time below range. A 72-h fasting test revealed inappropriately high proinsulin and C-peptide levels, indicating endogenous hyperinsulinemia. The patient was receiving sacubitril/valsartan for heart failure. Upon discontinuation of this treatment due to worsening renal function, hypoglycemic episodes resolved completely, and a repeat fasting test was normal. This is, to our knowledge, the first case report describing sacubitril/valsartan-associated hypoglycemia in a patient post-gastric bypass surgery, and the first to document inappropriate insulin secretion under treatment using a fasting test. Preclinical data suggest that neprilysin inhibition may enhance insulin secretion, possibly via increased GLP-1 bioavailability. While sacubitril/valsartan has demonstrated cardiovascular benefit, its metabolic effects remain underrecognized. Given the growing number of patients who have undergone bariatric surgery and the widespread use of this medication, clinicians should consider its potential role in refractory hypoglycemia. Early identification may avoid unnecessary investigations and support appropriate therapeutic adjustments.