Dataset Information

Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitus.

ABSTRACT: AIM:To characterize the pharmacokinetic and pharmacodynamic properties of dasiglucagon, a novel, stable and liquid formulated glucagon analogue, during hypoglycaemic and euglycaemic conditions in adult patients with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS:In this randomized double-blind trial, 17 patients received four single subcutaneous doses (0.03, 0.08, 0.2 and 0.6 mg) of dasiglucagon (4 mg/mL formulation) under euglycaemic (plasma glucose [PG] 5.6 mmol/L [100 mg/dL]) or hypoglycaemic (PG 3.1-3.7 mmol/L [56-66 mg/dL]) conditions. For comparison, three doses (0.03, 0.08 and 0.2 mg) of a commercial glucagon formulation (Eli Lilly) were investigated at euglycaemia. RESULTS:Dasiglucagon led to a dose-dependent and rapid increase in PG levels across all doses tested (mean increases 30 minutes post-dosing of 2.2 to 4.4 mmol/L [39-80 mg/dL] from euglycaemia and 1.3 to 5.2 mmol/L [24-94 mg/dL] from hypoglycaemia), which was higher than the rises elicited by similar doses of commercial glucagon (1.7-3.9 mmol/L [30-71 mg/dL]). The median time (range) to an increase in PG of >1.1 mmol/L (20 mg/dL) was <20 (18-19.5) minutes with 0.03 mg dasiglucagon and, with higher doses, the median times ranged from 9 to 15 minutes (commercial glucagon 13-14 minutes). In hypoglycaemia, 0.03 and 0.08 mg dasiglucagon re-established normoglycaemia (PG ?3.9 mmol/L [70 mg/dL]) within median times of 14 and 10 minutes, respectively. Nausea and vomiting occurred more frequently with dasiglucagon than with commercial glucagon at identical doses which might be attributable to dasiglucagon's higher potency. CONCLUSION:Dasiglucagon rapidly increased PG at doses of 0.03 to 0.6 mg in a dose-dependent manner and, therefore, is a good candidate for use in dual-hormone artificial pancreas systems.

SUBMITTER: Hovelmann U

PROVIDER: S-EPMC6587565 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitus.

Hövelmann Ulrike U Olsen Minna Braendholt MB Mouritzen Ulrik U Lamers Daniela D Kronshage Birgit B Heise Tim T

Diabetes, obesity & metabolism 20181128 3

<h4>Aim</h4>To characterize the pharmacokinetic and pharmacodynamic properties of dasiglucagon, a novel, stable and liquid formulated glucagon analogue, during hypoglycaemic and euglycaemic conditions in adult patients with type 1 diabetes mellitus.<h4>Research design and methods</h4>In this randomized double-blind trial, 17 patients received four single subcutaneous doses (0.03, 0.08, 0.2 and 0.6 mg) of dasiglucagon (4 mg/mL formulation) under euglycaemic (plasma glucose [PG] 5.6 mmol/L [100 mg ...[more]

PMID: 30350477

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Project description:BackgroundHypoglycemia occurs in an appreciable number of individuals with type 2 diabetes mellitus (T2DM) who are receiving glycemic therapy. Iatrogenic hypoglycemia induces not only complications but also a substantial medical expense. Intervention for relevant risk factors may help avert severe hypoglycemia and enhance quality of life in at-risk individuals. This study investigates the relationship between body mass index (BMI) and plasma glucose concentration during iatrogenic hypoglycemia in people with T2DM.MethodsEnrollment criteria were people above 20 years of age, with existing diagnosis of T2DM, a documented plasma glucose level ≤70 mg/dL, and acute cognitive impairment requiring hospitalization. Participants were classified into two groups according to their BMI. Specifically, lower BMI subgroup denotes individuals whose BMI fall within lower half of the study population, and vice versa. Plasma glucose concentration, length of hospital stay, and serum electrolyte level at hospitalization were compared between these BMI subgroups. Moreover, multivariate regression analysis was performed to identify covariates associated with plasma glucose level during iatrogenic hypoglycemia.ResultsThis study enrolled 107 participants for whom 54 were assigned to a higher BMI subgroup and the remainder to a lower BMI subgroup. People with lower BMI harbored substantially reduced plasma glucose concentration during iatrogenic hypoglycemia compared to those with higher BMI (30.1 ± 9.6 mg/dL vs. 38.4 ± 12.3 mg/dL, P < 0.001). Nonetheless, the length of stay (6.2 ± 4.6 days vs. 5.7 ± 4.0 days, P = 0.77) and serum potassium level (3.7 ± 0.9 meq/L vs. 3.9 ± 0.8 meq/L, P = 0.14) were comparable between subgroups. Multivariate regression analysis identified BMI as a determinant of plasma glucose concentration in diabetic individuals with iatrogenic hypoglycemia (β coefficient: 0.72, P = 0.008).DiscussionIn individuals with T2DM who experience severe iatrogenic hypoglycemia, BMI influences the plasma glucose level at hospitalization. People with lower BMI harbored appreciably reduced plasma glucose concentration relative to their higher BMI counterparts. In lower weight people, therefore, appropriate dosing of antidiabetic medications, frequent self-monitoring of blood glucose level and adequate nutritional support may help avert more severe hypoglycemia. Overall, BMI potentially influences the severity of iatrogenic hypoglycemia in people with T2DM.

Dataset Information

Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitus.

Publications

Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitus.

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