10-LB: Dasiglucagon Ameliorates Postprandial Hypoglycemia after Roux-en-y Gastric Bypass

Abstract

Introduction: Postprandial hypoglycemia is a frequent and debilitating complication following Roux-en-Y gastric bypass (RYGB) without effective treatments. In a proof-of-concept study, we investigated the effects of dasiglucagon, a novel, stable glucagon analog, on postprandial hypoglycemia after RYGB. Methods: Ten RYGB-operated individuals with confirmed symptomatic postprandial hypoglycemia (plasma glucose concentration (PG) <3.5 mmol×L-1) completed a randomized crossover study consisting of three study days each including a standardized liquid mixed meal test (25 kJ per kg body mass; 50% carbohydrates, 35% fat and 15% protein). A subcutaneous injection of either placebo, 80 or 200 µg dasiglucagon (D80µg and D200µg) was administered after the postprandial PG peak, ten minutes before the projected time point where PG returned to fasting levels, using a subject-specific linear regression model. Blood sampling and assessment of hypoglycemic symptoms (Edinburgh Hypoglycemia Symptom Scale) were performed at fixed time intervals. Data were analyzed using linear mixed models and Tuckey’s corrections model for multiple comparisons. Results: Compared with placebo, treatment with both D80µg and D200µg significantly increased nadir PG (placebo: 3.0±0.2 mmol×L-1; D80µg: 3.9±0.3 mmol×L-1; D200µg: 4.5±0.2 mmol×L-1; P=0.002 and P=0.0002) and PG incremental area under the curve (iAUC70-240min) after drug administration (placebo: 752±19 mmol×L-1×min; D80µg: 917±22 mmol×L-1×min; D200µg: 992±28 mmol×L-1×min; P<0.0001 and P<0.0001). Moreover, both doses reduced time spent in hypoglycemia (<3.9 mmol×L-1) (placebo: 62.0±8 min; D80µg: 27.5±12 min; D200µg: 14.0±9 min; P=0.05 and P=0.003). There were no significant changes in hypoglycemic symptoms between the three study days. Conclusion: Administration of dasiglucagon effectively ameliorates postprandial hypoglycemia representing a promising new therapeutic option for management of postprandial hypoglycemia after RYGB. Disclosure C.K. Nielsen: None. C. Oehrstroem: None. U. Kielgast: None. D.L. Hansen: None. A. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Norgine B.V., Novo Nordisk A/S.