Dataset Information

Stability of Commercially Available Glucagon Formulation for Dual-Hormone Artificial Pancreas Clinical Use.

ABSTRACT:

Background

Available glucagon formulations are approved for immediate use after reconstitution for severe hypoglycemia emergency treatment. However, they are used in dual-hormone artificial pancreas (insulin and glucagon) studies through subcutaneous infusion pumps over 24 h. Chemical and physical stability of such glucagon use have not been reported in a comprehensive manner.

Materials and methods

Recombinant Glucagon DNA (Eli Lilly) was used. Compatibility and sterility of glucagon delivery through subcutaneous pump systems were verified. Glucagon degradation through liquid chromatography with tandem mass spectrometry (LC-MS/MS), fibrillation using intrinsic tryptophan fluorescence shift, and bioactivity through a cell-protein kinase A-based fluorescent bioassay were assessed over a range of different physical conditions (temperature, movement, and air bubbles).

Results

Subcutaneous infusion pump systems administered glucagon in sterile conditions and with comparable accuracy to insulin delivery; mean absolute relative difference of actual versus expected weights were 1.2% ± 1.1% for glucagon and 1.1% ± 0.5% for insulin (P = 0.9). In comparison to freshly reconstituted samples, glucagon analyzed through LC-MS/MS was intact at 93.0% ± 7.0% after 24 h (P = 0.42) and 83.04% ± 6.0% after 48 h (P = 0.02) of incubation in pumps at 32°C. Peak wavelengths for Trp fluorescence did not differ from samples exposed to air bubbles or movement whether incubated (in infusion sets for 24 h at 32°) immediately or 24- and 48-h poststorage at 4°C (P = 0.10, 0.70 and 0.80, respectively) and no significant differences in bioactivity (shifts in EC₅₀) were found for the same conditions (P = 0.13, 0.83, and 0.63).

Conclusion

Available glucagon formulations are chemically and physically stable, as well as compatible with delivery through subcutaneous infusion pumps over 24 h and can be used in long-term clinical trials.

SUBMITTER: Taleb N

PROVIDER: S-EPMC5653137 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Stability of Commercially Available Glucagon Formulation for Dual-Hormone Artificial Pancreas Clinical Use.

Taleb Nadine N Coriati Adèle A Khazzaka Christian C Bayonne Jonathan J Messier Virginie V Rabasa-Lhoret Rémi R

Diabetes technology & therapeutics 20170828 10

<h4>Background</h4>Available glucagon formulations are approved for immediate use after reconstitution for severe hypoglycemia emergency treatment. However, they are used in dual-hormone artificial pancreas (insulin and glucagon) studies through subcutaneous infusion pumps over 24 h. Chemical and physical stability of such glucagon use have not been reported in a comprehensive manner.<h4>Materials and methods</h4>Recombinant Glucagon DNA (Eli Lilly) was used. Compatibility and sterility of gluca ...[more]

PMID: 28846447

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Project description:BackgroundMost patients with type 1 diabetes do not achieve their glycemic targets. We aimed to assess the efficacy of glucose-responsive insulin and glucagon closed-loop delivery for controlling glucose levels in adults with type 1 diabetes.MethodsWe conducted a randomized crossover trial involving 15 adults with type 1 diabetes, comparing standard insulin-pump therapy with dual-hormone, closed-loop delivery. Patients were admitted twice to a clinical research facility and received, in random order, both treatments. Each 15-hour visit (from 1600 to 0700) included an evening exercise session, followed by a medium-sized meal, a bedtime snack and an overnight stay. During visits that involved closed-loop delivery, basal insulin and glucagon miniboluses were delivered according to recommendations based on glucose sensor readings and a predictive dosing algorithm at 10-minute intervals. During visits involving standard insulin-pump therapy (control visits), patients used conventional treatment.ResultsDual-hormone closed-loop delivery increased the percentage of time for which patients' plasma glucose levels were in the target range (median 70.7% [interquartile range (IQR) 46.1%-88.4%] for closed-loop delivery v. 57.3% [IQR 25.2%-71.8%] for control, p = 0.003) and decreased the percentage of time for which plasma glucose levels were in the low range (bottom of target range [< 4.0 mmol/L], 0.0% [IQR 0.0%-3.0%] for closed-loop delivery v. 10.2% [IQR 0.0%-13.0%] for control, p = 0.01; hypoglycemia threshold [< 3.3 mmol/L], 0.0% [IQR 0.0%-0.0%] for closed-loop delivery v. 2.8% [IQR 0.0%-5.9%] for control, p = 0.006). Eight participants (53%) had at least 1 hypoglycemic event (plasma glucose < 3.0 mmol/L) during standard treatment, compared with just 1 participant (7%) during closed-loop treatment (p = 0.02).InterpretationDual-hormone, closed-loop delivery guided by advanced algorithms improved short-term glucose control and reduced the risk of hypoglycemia in a group of 15 adults with type 1 diabetes.Trial registrationClinicalTrials.gov, no. NCT01297946.

Project description:ObjectivesMap the current landscape of commercially available artificial intelligence (AI) software for radiology and review the availability of their scientific evidence.MethodsWe created an online overview of CE-marked AI software products for clinical radiology based on vendor-supplied product specifications ( www.aiforradiology.com ). Characteristics such as modality, subspeciality, main task, regulatory information, deployment, and pricing model were retrieved. We conducted an extensive literature search on the available scientific evidence of these products. Articles were classified according to a hierarchical model of efficacy.ResultsThe overview included 100 CE-marked AI products from 54 different vendors. For 64/100 products, there was no peer-reviewed evidence of its efficacy. We observed a large heterogeneity in deployment methods, pricing models, and regulatory classes. The evidence of the remaining 36/100 products comprised 237 papers that predominantly (65%) focused on diagnostic accuracy (efficacy level 2). From the 100 products, 18 had evidence that regarded level 3 or higher, validating the (potential) impact on diagnostic thinking, patient outcome, or costs. Half of the available evidence (116/237) were independent and not (co-)funded or (co-)authored by the vendor.ConclusionsEven though the commercial supply of AI software in radiology already holds 100 CE-marked products, we conclude that the sector is still in its infancy. For 64/100 products, peer-reviewed evidence on its efficacy is lacking. Only 18/100 AI products have demonstrated (potential) clinical impact.Key points• Artificial intelligence in radiology is still in its infancy even though already 100 CE-marked AI products are commercially available. • Only 36 out of 100 products have peer-reviewed evidence of which most studies demonstrate lower levels of efficacy. • There is a wide variety in deployment strategies, pricing models, and CE marking class of AI products for radiology.

Dataset Information

Stability of Commercially Available Glucagon Formulation for Dual-Hormone Artificial Pancreas Clinical Use.

Background

Materials and methods

Results

Conclusion

Publications

Stability of Commercially Available Glucagon Formulation for Dual-Hormone Artificial Pancreas Clinical Use.

Similar Datasets

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