Low-dose Dasiglucagon for Prevention of Insulin-Induced Hypoglycemia in People With Type 1 Diabetes

Steno Diabetes Centers

Status and phase: Completed; Phase 2

Conditions: Hypoglycemia; Type 1 Diabetes

Treatments: Drug: Dasiglucagon; Other: Carbohydrate (dextrose tablets)

Study type: Interventional

Funder types: Other

Identifiers

NCT04449692

H-20013256 (Registry Identifier)

2020-000551-12 (EudraCT Number)

Details and patient eligibility

About

The aim of the study is to compare the efficacy of low-dose dasiglucagon (Zealand Pharma, Denmark) to oral carbohydrate consumption for prevention of s.c. insulin-induced hypoglycemia in CSII- and MDI-treated people with type 1 diabetes.

Full description

Near-normalization of blood glucose levels through intensive insulin therapy has shown to reduce the risk of diabetes late complications, but the approach is associated with two major side effects: hypoglycemia and weight gain. Although management of hypoglycemia through oral carbohydrate consumption is generally effective, the approach can lead to excessive carbohydrate intake and cause rebound hyperglycemia. It has previously been demonstrated that subcutaneous (s.c.) low-dose glucagon can be utilized to effectively treat mild hypoglycemia in people with type 1 diabetes. However, the instability in aqueous solution of currently available glucagon and the need for reconstitution with sterile water immediately prior to administration has limited its clinical role outside emergency settings. Due to the stability and ready-to-use formulation, dasiglucagon does not hold the limitations known for the currently available glucagon preparations.

The aim of this randomized, partially single-blinded, three-arm cross-over study is to compare the efficacy of low-dose dasiglucagon (80 and 120 μg) to oral carbohydrate (15 g) consumption for prevention of s.c. insulin-induced hypoglycemia in CSII- and MDI-treated people with type 1 diabetes. On each study visit (separated by ≥ 3 days), an initial insulin bolus will be administered (at t = 0) aiming for a plasma glucose (PG) level of 3.0 mmol/l. When reaching 4.5 mmol/l, the intervention (s.c. dasiglucagon or oral carbohydrates) will be administered (t-intervention = 0), whereafter PG will me monitored for an additional 180 min.

Enrollment: 20 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18-64 years
• Duration of T1D ≥ 3 years
• Use of CSII or MDI therapy for ≥ 6 months
• Current use of Novorapid (change from another fast-acting insulin to Novorapid prior to study initiation is allowed)
• HbA1c ≤ 8.0%
• Regular use of carbohydrate counting in the judgement of the investigator

Exclusion criteria

• Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to study start
• History of allergy or intolerance to glucagon or glucagon-like products
• Patients with pheochromocytoma
• Clinically significant ECG abnormalities
• Females who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (sterilization, intrauterine device, contraceptive pill, patch or injection)
• Inability to understand the individual information and to give informed consent
• Current participation in another clinical trial that, in the judgment of the principle investigator, will compromise the results of the study or the safety of the subject
• Other concomitant medical or psychological condition that, according to the investigator's assessment, makes the individual unsuitable for study participation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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20 participants in 3 patient groups

80 µg s.c. dasiglucagon

Experimental group

Description:

80 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l

Treatment:

Drug: Dasiglucagon

120 µg s.c. dasiglucagon

Experimental group

Description:

120 µg of dasiglucagon will be administered subcutaneously when plasma glucose levels reach 4.5 mmol/l

Treatment:

Drug: Dasiglucagon

15 g oral carbohydrate (dextrose tablets)

Active Comparator group

Description:

15 g of oral carbohydrate (dextrose tablets) will be administered when plasma glucose levels reach 4.5 mmol/l

Treatment:

Other: Carbohydrate (dextrose tablets)