Glucagon in the Diagnosis and Treatment of Hypoglycaemia

Marks, V.

doi:10.1007/978-3-642-69019-8_33

Cited by 2 publications

(1 citation statement)

References 98 publications

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“…1 Glucagon is used therapeutically to treat severe hypoglycemia, particularly in patients with diabetes when intravenous glucose is unavailable. 2,3 Glucagon is also used intravenously to relax the intestinal tract to facilitate radiographic examination of the upper and lower gastrointestinal tract. 3,4 Although glucagon is used to treat diabetic hypoglycemia, it may induce hyperglycemia in patients with diabetes when used for radiologic purposes if the patients are in good metabolic control.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and glucodynamic comparisons of recombinant and animal‐source glucagon after IV, IM, and SC injection in healthy volunteers

Graf

Woodworth

Seger

et al. 1999

Journal of Pharmaceutical Sciences

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The structure of the hormone glucagon is identical among humans and several species of other mammals. Equivalence of recombinant glucagon (rG) to animal-source glucagon (aG) was assessed in this two-part, open-label, randomized study. Part I was a four-way crossover intravenous dose-ranging study of rG (pH 2.8) involving 12 subjects. Part II was a six-way crossover study of 29 subjects comparing rG (diluent pH 2.0 and 2.8) with aG administered subcutaneously (sc) and intramuscularly (im). Maximum glucagon plasma concentrations (C(max)) and area under the glucagon concentration curve (AUC) were calculated. Additionally, maximum blood glucose concentrations (BG(max)), maximum absolute BG excursion (MAE), and area under the glucose concentration curve from time of dosing to return to baseline (AUC(rtb)) were calculated. The primary focus was equivalence of the formulation intended for marketing (rG pH 2.0) to aG. Administration of rG pH 2.0 through the im route demonstrated equivalence to aG for all pharmacokinetic and glucodynamic comparisons. Subcutaneous administration of rG pH 2.0 demonstrated standard bioequivalence for AUC (5.87 versus 6.63 ng x h/mL; NS) and near equivalence for C(max) (7.94 versus 9.12 ng/mL; p < 0.05). rG pH 2.0 showed glucodynamic equivalence to aG (BG(max), 136 versus 133 mg/dL; MAE, 50.0 versus 47.4 mg/dL, respectively) and statistically greater AUC(rtb) values (151 versus 126 mg x h/dL, p < 0. 05). rG and aG were equally safe and well tolerated. In conclusion, rG provides equivalent safety and efficacy to aG.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and glucodynamic comparisons of recombinant and animal‐source glucagon after IV, IM, and SC injection in healthy volunteers

Graf

Woodworth

Seger

et al. 1999

Journal of Pharmaceutical Sciences

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Analysis of Glucose Responsive Glucagon Therapeutics using Computational Models of the Glucoregulatory System

Alizadehmojarad,

Yang,

Gong

et al. 2024

Adv Healthcare Materials

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Glucose‐responsive glucagon (GRG) therapeutics are a promising technology for reducing the risk of severe hypoglycemia as a complication of diabetes mellitus. Herein, the performance of candidate GRGs in the literature by modeling the kinetics of activation and connecting them as input into physiological glucoregulatory models is evaluated and projected the two distinct GRG designs, experimental results reported in Wu et al. (GRG‐I) and Webber et al. (GRG‐II) is considered. Both are evaluated using a multi‐compartmental glucoregulatory model (IMPACT) and used to compare in‐vivo experimental data of therapeutic performance in rats and mice. For GRG‐I and GRG‐II, the total integrated glucose material balances are overestimated by 41.5% ± 14% and underestimated by 24.8% ± 16% compared to in‐vivo time‐course data, respectively. These large differences to the relatively simple computational descriptions of glucagon dynamics in the model, which underscores the urgent need for improved glucagon models is attributed. Additionally, therapeutic insulin and glucagon infusion pumps are modeled for type 1 diabetes mellitus (T1DM) human subjects to extend the results to additional datasets. These observations suggest that both the representative physiological and non‐physiological models considered in this work require additional refinement to successfully describe clinical data that involve simultaneous, coupled insulin, glucose, and glucagon dynamics.

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Glucagon in the Diagnosis and Treatment of Hypoglycaemia

Cited by 2 publications

References 98 publications

Pharmacokinetic and glucodynamic comparisons of recombinant and animal‐source glucagon after IV, IM, and SC injection in healthy volunteers

Pharmacokinetic and glucodynamic comparisons of recombinant and animal‐source glucagon after IV, IM, and SC injection in healthy volunteers

Analysis of Glucose Responsive Glucagon Therapeutics using Computational Models of the Glucoregulatory System

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