The Glucagonotropic Effect of GIP Is Negated During Insulin-Induced Hypoglycemia in Type 1 Diabetes: A Randomized, Placebo-Controlled, Crossover Study.

Sørum, Nikolaj E; Warnøe, Julie; Holst, Jens J; Hartmann, Bolette; Gasbjerg, Lærke S; Størling, Joachim; Bergmann, Marianne L; Dejgaard, Thomas F et al. · Diabetes · 2026

rct · Level II

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Abstract

The glucose-dependent glucagonotropic effects of glucose-dependent insulinotropic polypeptide (GIP) variants in type 1 diabetes (T1D) are incompletely understood. We investigated whether native full-length GIP[1-42] and its truncated variant GIP[1-30]NH2 increase glucagon concentrations during insulin-induced hypoglycemia in individuals with T1D. During euglycemia, both GIP variants increased glucagon [statistically significantly for GIP(1-30)NH2 only] and norepinephrine, but insulin suppressed glucagon levels similarly across interventions. High-dose GIP[1-42] was associated with slightly reduced glucose requirements during recovery from hypoglycemia, suggestive of increased hepatic glucose production through either glucagon or norepinephrine action.