The balance between insulin and glucagon responses to glucose-dependent insulinotropic polypeptide (GIP) may vary with glycemic status in type 2 diabetes mellitus (T2DM). An analysis published in Diabetes, Obesity and Metabolism evaluated postprandial GIP responses in relation to glucagon and insulin secretion across different levels of glycemic control.

Data were analyzed from three clinical studies, including mixed-meal testing in 79 individuals with T2DM, intraduodenal fat infusion in 15 individuals with T2DM, and intraduodenal glucose infusion in 10 individuals with T2DM and 10 healthy participants. Associations between postprandial GIP and glucagon or insulin responses were assessed, with subgroup analyses based on glycated hemoglobin (HbA1c) levels.

Following mixed-meal ingestion, early postprandial glucagon secretion (0–30 minutes) increased in relation to GIP, with stronger relationships observed at higher HbA1c levels. In contrast, the insulinogenic index showed a relationship with GIP only in subgroups with HbA1c below 7.0%. During intraduodenal fat infusion, glucagon and GIP responses were strongly aligned in T2DM. After intraduodenal glucose infusion, early glucagon and GIP increments were closely aligned in T2DM but not in healthy individuals.

These findings indicate variation in GIP-related responses across levels of glycemic control in T2DM, with differences observed in insulin and glucagon patterns.