American Diabetes Association
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Dasiglucagon Treatment of Postprandial Hypoglycemia After Gastric Bypass: a Randomized, Double-blind, Placebo-controlled Trial

posted on 2023-10-11, 17:51 authored by Casper K. Nielsen, Caroline C. Øhrstrøm, Inas J. K. Houji, Mads M. Helsted, Liva S. L. Krogh, Nicklas J. Johansen, Bolette Hartmann, Jens J Holst, Tina Vilsbøll, Filip K. Knop

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. NCT04836273.


Funding: This investigator-initiated trial was supported by an unrestricted grant from Zealand Pharma A/S, who also supplied dasiglucagon, placebo and the reusable multi-dose pen used for the administration of placebo/dasiglucagon. Zealand Pharma assisted in developing the study protocol and provided statistical consultation. However, the funder played no role in determining the study design, collecting data, data analysis, data interpretation, or writing the manuscript.