Exploring low-dose glucagon for exercise-induced hypoglycaemia in type 1 diabetes: A randomised controlled trial.

Aims: This study was designed to compare the effectiveness of a single subcutaneous (s.c.) glucagon dose versus the same total dose split into a dose before and after and placebo (PBO) in preventing exercise-induced hypoglycaemia in adults with type 1 diabetes (T1D).

Methods: Twenty-two adults with T1D participated in a randomised, single-blinded, three-arm crossover study. Participants underwent a 60-min bout of moderate-intensity cycle ergometry (~50% HRmax) in fasted state, followed by 2 h of rest. Plasma glucose (PG) concentrations were monitored at 5- and 15-minute intervals. Participants were randomly assigned to receive two separate injections before (t = 0 min) and just after (t = 60 min) exercise: (i) 150 μg s.c. glucagon (G150) before and PBO after; (ii) 75 μg s.c. glucagon (G75*2) before and after; or (iii) PBO before and after. Insulin pump users reduced their basal insulin rate by 50% during cycling.

Results: The occurrence of hypoglycaemia did not significantly differ between arms (G150: 7, G75*2: 5 and PBO: 6 events, p = 0.078). Mean PG levels throughout the trial were lower in the PBO arm compared to both glucagon arms (G150: 8.6 ± 2.9, G75*2: 8.9 ± 3.4 and PBO: 7.3 ± 2.6 mmol/L, p = 0.015). Time spent with PG in target range (3.9-10.0 mmol/L) was higher in the PBO arm versus both glucagon arms (G150: 63.9 ± 38.9%, G75*2: 60.0 ± 34.1% and PBO: 82.7 ± 29.6%, p = 0.005), driven by less time above range (G150: 32.9 ± 41.3%, G75*2: 35.9 ± 36.4% and PBO: 13.2 ± 30.2%, p = 0.007).

Conclusions: Low-dose native glucagon did not offer any advantages in preventing exercise-induced hypoglycaemia in individuals with T1D, regardless of glucagon dosing variations.