Dasiglucagon Treatment for Postprandial Hypoglycemia After Gastric Bypass: A Randomized, Double-Blind, Placebo-Controlled Trial

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*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

2 Citationer (Scopus)

Abstract

OBJECTIVE
Postbariatric hypoglycemia affects >50% of individuals who have undergone Roux-en-Y gastric bypass surgery. 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 was recently shown to mitigate postbariatric 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 in Denmark. The study included 24 individuals who had undergone Roux-en-Y gastric bypass surgery (n = 23 women) with continuous glucose monitor–verified postbariatric hypoglycemia (≥15 min at <3.9 mmol/L three or more times per week) randomly assigned to two treatment periods of 4 weeks of self-administered subcutaneous dasiglucagon at 120 μg or placebo. The primary and key secondary outcomes were continuous glucose monitor–captured percentage of time in level 1 and 2 hypoglycemia (<3.9 and <3.0 mmol/L), respectively.

RESULTS
Compared with placebo, treatment with dasiglucagon significantly reduced time in level 1 hypoglycemia by 33% (−1.2 percentage points; 95% CI −2.0 to −0.5; P = 0.002) and time in level 2 hypoglycemia by 54% (−0.4 percentage points; 95% CI −0.6 to −0.2; P < 0.0001). Furthermore, dasiglucagon corrected hypoglycemia within 15 min in 401 of 412 self-administrations, 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, 4 weeks of self-administered dasiglucagon effectively reduced clinically relevant hypoglycemia in individuals who had undergone Roux-en-Y gastric bypass surgery.
OriginalsprogEngelsk
TidsskriftDiabetes Care
Vol/bind46
Udgave nummer12
Sider (fra-til)2208-2217
Antal sider10
ISSN0149-5992
DOI
StatusUdgivet - 2023

Bibliografisk note

Publisher Copyright:
© 2023 by the American Diabetes Association.

Citationsformater