Dasiglucagon Effectively Mitigates Postbariatric Postprandial Hypoglycemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

<b>OBJECTIVE</b> 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 post-bariatric hypoglycemia (PBH). <p><a><b>RESEARCH DESIGN AND METHODS </b></a>In a randomized, double-blind, placebo-controlled crossover trial, 10 RYGB-operated participants with continuous glucose monitoring (CGM)-verified PBH were randomized to three trial days, each consisting of a 240-minute standardized liquid mixed meal test (MMT) with the subcutaneous injection of either placebo, 80 µg, or 200 µg dasiglucagon. </p> <p><a><b>RESULTS </b></a><a></a>Compared with placebo, treatment with both 80 and 200 µg dasiglucagon raised nadir plasma glucose (PG) (placebo: 3.0 ± 0.2 mmol/L (mean ± standard error of the mean (SEM)); 80 µg dasiglucagon: 3.9 ± 0.3 mmol/L,<i> P </i>= 0.002; 200 µg dasiglucagon: 4.5 ± 0.2 mmol/L, <i>P </i>= 0.0002) and reduced time in hypoglycemia (PG < 3.9 mmol/L) <a>by 70.0</a> minutes (<i>P </i>= 0.030 and <i>P</i> = 0.008).</p> <a><b>CONCLUSION </b></a>Single-dose administration of dasiglucagon effectively mitigated postprandial hypoglycemia.