Acarbose and Pasireotide Reduce Hypoglycemia in Roux-en-Y Gastric Bypass Operated Subjects

Abstract

Introduction: Hypoglycemia is a severe complication after Roux-en-Y gastric bypass (RYGB), with no effective treatment options. We investigated the glucose stabilizing effects of five therapeutic agents in RYGB operated subjects with hypoglycemia. Methods: In a randomized crossovers study, 11 RYGB operated subjects with documented hypoglycemia (blood glucose <70.2 mg/dL) underwent six separate meal tolerance tests (Fresubin Energy Drink) preceded by either: no treatment (NT), acarbose 50 mg (A), sitagliptin 100 mg for 1 week (S), verapamil 120 mg for 1 week (V), liraglutide 1.2 mg for 3 weeks (L) or pasireotide 300 µg (P). Blood samples were drawn at fixed time intervals from -20 to 180 minutes. Hormonal responses were calculated as the incremental area under the curve (iAUC), and the glucose response was further specified as the area above (+iAUC) and below (-iAUC) baseline values. Data were analyzed by use of linear mixed models. Results: Treatment with A and P significantly reduced -iAUCglucose (NT: 106±14 mmolxL-1xmin (mean±SEM) A: 63±14 mmolxL-1xmin, p=0.02; P: 0±0 mmolxL-1xmin, p<0.0001). Additionally A reduced +iAUCglucose, whereas P increased this area (NT: 182±18 mmolxL-1xmin; A: 78±18 mmolxL-1xmin, p=0.0008; P: 1,144±62 mmolxL-1xmin, p<0.0001). Time spent in hypoglycemia decreased with both A and P (NT: 48±12 min; A: 5±3 min, p=0.02; P: 0±0 min, p<0.0001), whereas time in hyperglycemia (>140.4 mg/dL) decreased with A but increased with P (NT: 29±4 min; A: 5±5 min, p=0.0017; P: 159±6 min, p<0.0001). Treatment with A and P both reduced iAUCinsulin (NT: 534±8 nmolxL-1xmin; A: 22±3 nmolxL-1xmin, p=0.0009; P: 14±2 nmolxL-1xmin, p<0.0001). Treatment with S, V and L did not have a significant impact on any of the measurements. Conclusion: Acarbose reduced both hypoglycemia and hyperglycemia, whereas pasireotide resolved hypoglycemia, but at the cost of increased hyperglycemia. Both acarbose and pasireotide can be considered in the treatment of hypoglycemia after RYGB. Disclosure C. øhrstrôm: None. U. Kielgast: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., AstraZeneca. Research Support; Self; Danish Diabetes Academy, Novo Nordisk Foundation. Other Relationship; Self; Antag Therapeutics. Other Relationship; Spouse/Partner; Antag Therapeutics. D. Worm: None. D.L. Hansen: None.