Post-Bariatric Hypoglycemia (PBH) Refractory to Conventional Therapies: The Combined Effect of Very High Doses of Glucagon-Like Receptor Agonist (GLP1-RA) and a Low Dose of Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i)

Introduction:
As the number of bariatric surgeries in the United States plateaus at nearly 200,000, the prevalence of post-bariatric hypoglycemia (PBH) is escalating. Since the pathophysiology driving PBH is not fully understood, treatment for PBH can be challenging in the clinical practice. Most recently, the use of GLP1-RA or SGLT2i have been reported as monotherapy options for PBH. We are presenting the case of a patient without diabetes who failed conventional therapy for her persistent PBH and dumping syndrome but was successfully treated with very high doses of

Case Description:
A 50-year-old Hispanic woman was referred to endocrinology with an 8-year history of recurrent syncope due to hypoglycemia. She was diagnosed with non-insulinoma pancreatogenic hypoglycemia complicated by PBH and dumping syndrome. She had a history of Roux-en-Y gastric bypass 10 years prior. Initially, she attempted diet modification, by eating less than 20 grams of carbohydrates per meal, with no improvement. Next, she trialed acarbose, which resulted in ongoing hypoglycemic events and gastrointestinal side effects. Intermittent-scanning Continuous Glucose Monitor (CGM) revealed 4% Target Below Range (TBR, < 70 mg/dL) off of acarbose despite eating every 2 hours to avoid hypoglycemia. Her hypoglycemic events were confirmed with a glucometer. We started her on Octreotide 50 mcg sq twice daily (BID), which improved TBR to 1% but resulted in relentless constipation. To regulate her bowels, her Octreotide was adjusted to 25 mcg AM and 50 mcg PM, but her TBR increased to 3%. With the addition of Liraglutide 0.6 mg sq daily to Octreotide 50 mcg BID, her constipation was unbearable, and her TBR was 2%. She remained on Octreotide 50 mcg BID and Liraglutide was up-titrated to 1.2 mg daily (TBR 4%) and then 1.8mg daily (TBR 4%). Octreotide was discontinued. On liraglutide 2.4mg daily alone, she continued without nocturnal hypoglycemia. She noted improvement in both her gastrointestinal side effects and her post-prandial hypoglycemia (TBR 3%). The dose of Liraglutide was maximized to 3 mg daily. Her CGM was changed to real-time CGM, and her TBR was 2.4%. Empagliflozin 10 mg daily was added to Liraglutide 3 mg daily, and her hypoglycemia instantly, and completely resolved with a sustained TBR of 0%.

Discussion:
Very high doses of Liraglutide combined with a low dose of empagliflozin corrected PBH to TBR 0% and resolved the dumping syndrome symptoms. This combination therapy should be considered in patients with PBH not responding to conventional anti-hypoglycemic monotherapies.