Dasiglucagon Treatment of Postprandial Hypoglycemia After Gastric Bypass: a Randomized, Double-blind, Placebo-controlled Trial
Objective: Post-bariatric hypoglycemia affects more than 50% of Roux-en-Y gastric bypass-operated individuals. Despite the often debilitating nature of this complication, existing treatment options are limited and often inefficient. Dasiglucagon is a stable glucagon analog available in a ready-to-use formulation and recently shown to mitigate post-bariatric hypoglycemia in experimental settings. Here we aimed to evaluate the hypoglycemic hindering potential of dasiglucagon in an outpatient trial.
Research Design and Methods: We conducted a randomized, double-blind, placebo-controlled, crossover, proof-of-concept study at the Center for Clinical Metabolic Research at Gentofte Hospital Denmark. The study included 24 Roux-en-Y gastric bypass-operated individuals (23 females) with continuous glucose monitor-verified post-bariatric hypoglycemia (≥15 minutes, <3.9 mmol/L, ≥3 times/week) randomly assigned to two four-week treatment periods of self-administered subcutaneously 120 µg dasiglucagon or placebo. The primary and key secondary outcome were continuous glucose monitor-captured percentage of time in level 1 & 2 hypoglycemia (<3.9 & <3.0 mmol/L, respectively).
Results: Compared with placebo, treatment with dasiglucagon significantly reduced time in level 1 hypoglycemia by 33% (−1.2%-points; 95% CI −2.0 to −0.5, P=0.002) and time in level 2 hypoglycemia by 54% (−0.4%-points; 95% CI −0.6 to −0.2, P<0.0001). Furthermore, dasiglucagon corrected hypoglycemia within 15 minutes in 401 of 412 self-administrations as compared with 104 of 357 placebo self-administrations (97.3% vs 29.1% correction of hypoglycemia rate, P<0.001). Dasiglucagon was generally well tolerated, with mostly mild to moderate adverse events of nausea.
Conclusions: Compared with placebo, four weeks of self-administered dasiglucagon effectively reduced clinically relevant hypoglycemia in Roux-en-Y gastric bypass-operated individuals. ClinicalTrials.gov: NCT04836273.