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Early dumping and post-bariatric hypoglycemia (PBH) are often addressed as two separate postprandial complications after Roux-en-Y gastric bypass (RYGB). The aim of the study was to evaluate the occurrence of early dumping in RYGB-operated individuals with PBH with and without treatment intervention. Eleven RYGB-operated women with documented PBH each underwent a baseline liquid mixed meal test (MMT) followed by five MMTs preceded by treatment with: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks, and pasireotide 300 μg as a single dose. Repetitive venous blood sampling and continuous electrocardiogram recordings were performed at fasting and during a 3-h postprandial period. During the baseline MMT, there was a significant increase in HR (from 65 ± 2 to 90 ± 4 bpm, p

OBJECTIVE To investigate the efficacy and safety of dasiglucagon, a novel stable glucagon analog in a liquid formulation, in Roux-en-Y gastric bypass (RYGB)–operated individuals suffering from postbariatric hypoglycemia (PBH). RESEARCH DESIGN AND METHODS In a randomized, double-blind, placebo-controlled, crossover trial, 10 RYGB-operated participants with continuous glucose monitoring–verified PBH were randomly assigned to 3 trial days, each consisting of a 240-min standardized liquid mixed-meal test with the subcutaneous injection of placebo or 80 μg or 200 μg dasiglucagon. RESULTS Compared with placebo, treatment with both 80 and 200 μg dasiglucagon raised nadir plasma glucose (PG) (placebo: 3.0 ± 0.2 mmol/L [mean ± SEM]; 80 μg dasiglucagon: 3.9 ± 0.3 mmol/L, P = 0.002; 200 μg dasiglucagon: 4.5 ± 0.2 mmol/L, P = 0.0002) and reduced time in hypoglycemia (PG CONCLUSIONS Single-dose administration of dasiglucagon effectively mitigated postprandial hypoglycemia.

Roux-en-Y gastric bypass (RYGB) is one of the most common and successful bariatric surgeries. However, more than half of RYGB-operated individuals may suffer from post-bariatric hypoglycaemia (PBH) characterised by traditional hypoglycaemic symptoms occurring 1 to 4 hours after meal intake. The mechanisms underlying PBH most likely relate to accelerated delivery of nutrients to the small intestine resulting in unretarded nutrient absorption, large elevations in postprandial plasma glucose concentrations (constituting a potent insulin secretory stimulus), and grossly elevated postprandial plasma levels of the insulinotropic gut-derived hormone glucagon-like peptide 1 (GLP-1) potentiating glucose-stimulated insulin secretion. Based on previous findings that circulating GLP-1 concentrations increased by ~100% during insulin-induced hypoglycaemia before but not after RYGB, Almby et al. explored whether exogenous GLP-1 may protect against PBH. They performed hyperinsulinaemic hypoglycaemic clamps with concomitant infusion of the GLP-1 analogue exenatide and saline, respectively, in individuals who had undergone RYGB surgery. Infusion with exenatide during hypoglycaemia had no plasma glucose-raising effects, did not increase the counterregulatory glucagon response, and did not affect symptom scores. In the present commentary, potentially important implications derived from the study by Almby et al. published in the August issue of EJE, are discussed in the light of previous observations on GLP-1 receptor agonist treatment in PBH. While the findings by Almby et al. do not provide a solution for patients with PBH, they contribute to the knowledge base needed to address the growing problem of PBH.

Post-bariatric hypoglycemia (PBH) can be a serious complication after Roux-en-Y gastric bypass (RYGB), and treatment with somatostatin analogs has been suggested. We investigated the acute effects of three different doses of pasireotide (75 μg, 150 μg, and 300 μg) on the postprandial glucose metabolism in five RYGB-operated individuals with PBH using a mixed meal test. All three doses prevented hypoglycemia but were associated with a notable increase in postprandial hyperglycemia. Moreover, all doses greatly diminished insulin, C-peptide, and glucagon-like peptide-1 responses. Considering its strong hyperglycemic potential, we suggest that pasireotide should be administered carefully in RYGB-operated individuals with PBH, and if necessary, a 75 μg dose seems sufficient to prevent hypoglycemia.

Introduction: Early dumping (ED) and postprandial hypoglycemia (PH) are often addressed as two separate complications after Roux-en-Y gastric bypass (RYGB) although symptoms overlap. We investigated the occurrence of ED in RYGB-patients with PH and potential mechanisms. Methods: In a randomized cross-over study, 11 RYGB-patients with confirmed PH (blood glucose Results: With NT, all patients had ΔHR ≥ 15 bpm within the first 35 minutes of the MMT (27 ± 3 bpm, mean ± SEM) corresponding to a 44 ± 4% increase in HR. Peak HR occurred at the same time as peak levels of glucose and GLP-1 (26 ± 2, 31 ± 2, 30 ± 2 minutes; p>0.23) and HR values were positively correlated with glucose, insulin and GLP-1 concentrations (r=0.44, r=0.41, r=0.56; p Conclusion: RYGB-patients with PH have postprandial HR increments suggestive of ED, indicating that PH and ED constitute a combined post-surgical complication. Insulin and GLP-1 are potential mediators driving the HR increments. Disclosure C. Øhrstrôm: None. D. Worm: None. U. Kielgast: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Eli Lilly and Company, Sanofi. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. D.L. Hansen: None.

AIM To investigate the effects of acarbose, sitagliptin, verapamil, liraglutide and pasireotide on post-bariatric hypoglycaemia (PBH) after Roux-en-Y gastric bypass. MATERIALS AND METHODS In a randomized crossover study, 11 women who had undergone Roux-en-Y gastric bypass and had documented hypoglycaemia were each evaluated during a baseline period without treatment and during five treatment periods with the following interventions: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks and pasireotide 300 μg as a single dose. Treatment effects were evaluated by a mixed-meal tolerance test (MMTT) and, for all treatment periods except pasireotide, by 6 days of continuous glucose monitoring (CGM). RESULTS Treatment with acarbose and treatment with pasireotide both significantly lifted nadir glucose levels (mean ± SEM 3.9 ± 0.2 and 7.9 ± 0.4 vs 3.4 ± 0.2; P

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 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, p140.4 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 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.