Glucagon enhances subcutaneous insulin absorption: Pilot experiments in pigs

Delayed subcutaneous (SC) insulin absorption remains one of the major barriers to optimal blood glucose control in people with type 1 diabetes and to the development of a fully automated artificial pancreas with SC insulin delivery. Our recent proof of concept study demonstrated that injecting 0.1 mg glucagon at the SC insulin (NovoRapid®) injection site enhances insulin absorption in a porcine model. Present experiments investigate the pharmacokinetics of Lyumjev®, the fastest-acting insulin currently available, when micro-doses of glucagon are co-injected at the same SC site.

20 anesthetized pigs were administered 10 IU of Lyumjev® SC. Animals were assigned to either a glucagon group (n = 12), receiving micro-doses of glucagon at the same subcutaneous injection site as insulin, or a control group (n = 8), receiving Lyumjev® only. Arterial blood samples were collected over a 210-minute period to measure glucose, insulin, and glucagon concentrations.

Compared with Lyumjev® alone, the addition of glucagon to Lyumjev® was associated with an approximately 21% higher mean C_max (58 vs 48 mU/L) and a 17% earlier T_max (25 vs 30 min). Early insulin exposure increased by 109% during the first 15 minutes and by 60% during the first 30 minutes following the addition of glucagon to Lyumjev® compared with Lyumjev® alone (AUC₀-₁₅: 654 vs 313 mU·min/L and AUC₀-₃₀: 1506 vs 942 mU·min/L, respectively).

These experiments in pigs suggest that micro-amounts of glucagon, when injected at the same SC site as insulin, may speed up and enhance the early absorption of a single SC insulin bolus.