Glucagon plays a critical role in counteracting hypoglycemia in type 1 diabetes, yet strategies to enhance its secretion during insulin-induced hypoglycemia remain limited. Findings from a randomized, double-blind, placebo-controlled crossover study presented at the European Association for the Study of Diabetes (EASD) 2025 evaluated the impact of exogenous glucose-dependent insulinotropic polypeptide (GIP[1-42]) and its truncated variant GIP[1-30]NH2 on glucagon secretion in this context.

Ten adults with type 1 diabetes (mean age 31 years, mean body mass index 24 kg/m², mean HbA1c 48.8 mmol/mol) underwent five hypoglycemic clamp experiments with intravenous infusion of GIP[1-42] (4 or 8 pmol/kg/min), GIP[1-30]NH2 (4 or 8 pmol/kg/min), or placebo during continuous insulin administration. Both GIP variants elevated plasma glucagon levels at 30 minutes compared with placebo, although insulin-induced hypoglycemia abolished this effect. High-dose GIP[1-42] infusion reduced the amount of glucose required for recovery, suggesting a protective benefit.

These results indicate that exogenous GIP can stimulate glucagon during normal glucose levels, but the effect is lost during hypoglycemia, with potential therapeutic implications for optimizing glucose recovery in type 1 diabetes. Further investigation is warranted.