Procedures
hypoglycaemia, palpitations, vomiting, UC, headache, nausea,, stomach ache, diabetes
DIABETES, ADVERSE EFFECTS, HYPOGLYCAEMIA
Participants completed two study periods, a 2 week UC period and a 2 week DASI period. Besides the hypoglycaemia management strategy (i.e. UC or low-dose dasiglucagon injection), all trial-related procedures were identical in the two study periods. In both periods, participants wore a Dexcom G6 (Dexcom, San Diego, CA, USA) CGM connected to a Dexcom G6 Receiver. They were worn and used according to applicable guidelines and inserted 24–72 h before the start of each study period. Participants were allowed to use and customise the Dexcom G6 alerts as they preferred; however, the selected settings were required to be used throughout the study, i.e. in both study periods, which participants were informed about prior to initiation of both study periods. To assess the physical activity level, participants also wore a blinded wrist-worn ActiGraph wGT3X-BT (ActiGraph, Pensacola, FL, USA) activity monitor. In addition, participants were instructed to register when they started and ended each exercise session as well as the intensity level (mild, moderate, intense) of these sessions. In both periods, participants were to continue their habitual use of their insulin pump, i.e. entering carbohydrate intake into the pump and, if part of their routine diabetes management, manually suspending or lowering the basal rate whenever needed. Finally, participants were instructed to fill out a questionnaire once a day stating whether they had experienced any episodes of nausea, headache, stomach ache, palpitations, vomiting or other adverse effects. The intensity of adverse effects was scored as mild, moderate or intense.In the UC period, participants managed episodes of impending or manifested hypoglycaemia as usual by consuming food and/or drinks. Thus, the type, amount and timing of the carbohydrates for hypoglycaemia management were as usual. In all cases where carbohydrates were consumed to prevent or treat an episode of hypoglycaemia (denoted ‘rescue carbohydrates’), participants were instructed to record the exact time and estimated amount of carbohydrates on the Dexcom G6 Receiver. Regular meals and snacks consumed without the intent to prevent or treat an episode of hypoglycaemia were not recorded on the Dexcom G6 Receiver but entered into the insulin pump as usual.In the DASI period, participants were instructed to manage impending or manifested episodes of hypoglycaemia by administering an s.c. injection of dasiglucagon into a lifted skinfold of the abdominal wall using the injection pen. Unused dasiglucagon cartridges were to be stored refrigerated (2–8°C), whereas cartridges inserted into the pen could be kept at room temperature for up to 1 month (note that Zegalogue [dasiglucagon marketed for treatment of severe hypoglycaemia] can be stored at room temperature for 12 months). The reusable multi-dose pen injector had a minimum and maximum dose of 40 μg and 320 μg, respectively, with incremental doses of 40 μg; however, participants were informed to use a fixed dose of 80 μg in all use scenarios throughout the study period. This dose was selected based on a recent inpatient study of the pharmacodynamic effects of different doses of dasiglucagon [In addition to the initial screening visit and completion of the two study periods, participants attended three in-clinic visits: a midway visit, an end-of-study visit and a follow-up visit scheduled 4 weeks after completion of the DASI period. At the follow-up visit, selected blood samples were collected and analysed for safety purposes. A detailed overview of the different visits and procedures is available in ESM Table 