Pen-administered low-dose dasiglucagon vs usual care for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions: a Phase II, randomised, open-label, two-period crossover trial

Abstract

Aims/hypothesis: Consumption of excess carbohydrates to manage hypoglycaemia can lead to rebound hyperglycaemia and promote weight gain. The objective of this trial was to evaluate the efficacy, safety and feasibility of pen-administered low-dose dasiglucagon for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions.

Methods: Twenty-four adults with insulin pump-treated type 1 diabetes (HbA_1c ≤70 mmol/mol [8.5%]) completed a randomised, open-label, two-period crossover study with 2 week periods. During the usual care and dasiglucagon intervention (DASI) periods, participants managed impending and manifested episodes of hypoglycaemia with regular carbohydrate consumption or pen-administered low-dose (80 μg) s.c. dasiglucagon, respectively. Glycaemic control was evaluated using continuous glucose monitoring (Dexcom G6) and event registration of prevention and treatment episodes.

Results: Compared with usual care, the mean difference (95% CI) in the DASI period for time in (3.9-10.0 mmol/l) and below (<3.9 mmol/l) range was 2.4 %-points (-0.7, 5.5) and -0.5 %-points (-1.2, 0.2), respectively. In the DASI period, recovery rate (time from hypoglycaemia treatment to euglycaemia) was 44% (11, 87) faster while total daily carbohydrate intake was reduced by 11% (-18, -3). Dasiglucagon use was safe and well tolerated with mild nausea being the most frequent adverse effect. Among the participants, 96% (p<0.0001) were likely to include dasiglucagon in their future routine management of hypoglycaemia.

Conclusions/interpretation: Use of low-dose dasiglucagon to prevent and treat non-severe hypoglycaemia during free-living conditions was safe, fast and efficacious while significantly reducing the total daily carbohydrate intake and yielding high treatment satisfaction.

Trial registration: ClinicalTrials.gov NCT04764968 FUNDING: The study was an investigator-initiated trial. Zealand Pharma supplied the investigational drug and device and provided financial support for the conduct of the trial.

Keywords: Dasiglucagon; Dual-hormone therapy; Hypoglycaemia; Phase 2; Randomised controlled trial; Type 1 diabetes.

Fig. 1

Efficacy profile. Blue lines/bars represent the DASI period; grey lines/bars represent the UC period. (a) Mean (±95% CI) change in SG after initial hypoglycaemia treatment. (b) One minus Kaplan–Meier plot of time from initial hypoglycaemia treatment (SG <3.9 mmol/l) to reaching euglycaemia (SG ≥3.9 mmol/l). Difference between the two periods is shown as RR. (c) Percentage of successful cases of hypoglycaemia treatment (initial SG ≤3.9 mmol/l followed by SG >3.9 mmol/l 30 min post treatment). (d) Percentage of successful cases of hypoglycaemia treatment without subsequent hyperglycaemia (SG >10 mmol/l within the first 2 h post treatment). (e) Percentage of successful cases of hypoglycaemia prevention (initial SG >3.9 mmol/l followed by ≤15 consecutive minutes of hypoglycaemia within the first 2 h post treatment). Statistical notation used: *p<0.05; **p<0.01. RR, rate ratio