TOPLINE:

In men with type 1 diabetes (T1D), an intravenous infusion of glucose‑dependent insulinotropic polypeptide (GIP) did not prevent hypoglycaemia when prandial insulin was given in excess and participants performed postmeal physical activity, but it modestly reduced the peak glucose levels observed after meals compared with the GIP receptor antagonist GIP(3-30)NH₂.

METHODOLOGY:

• Researchers in Denmark conducted a randomised crossover trial in 12 men with T1D (mean age, 26 years; mean diabetes duration, 11 years; mean A1c, 6.6%) to examine the effects of GIP on postprandial glucose excursions in a high-risk hypoglycaemic setting.
• Participants completed three study days at least 1 week apart, each involving a 4.5-hour intravenous infusion of either placebo, human GIP (6 pmol/kg/min), or the GIP receptor antagonist GIP(3-30)NH2 (1200 pmol/kg/min).
• To induce a high-risk hypoglycaemic state, infusions were started 30 minutes before a standardised 300 kcal mixed meal; participants took 125% of their usual insulin dose immediately before the meal and then cycled on an ergometer for 30 minutes.
• Blood was sampled periodically throughout each study day to measure levels of glucose, hormones, metabolites, and acetaminophen.
• Rescue glucose was provided if the plasma glucose level fell below 2.5 mmol/L.

TAKEAWAY:

• Compared with GIP(3-30)NH2, GIP infusion lowered postprandial glucose Cmax by 1.49 mmol/L (P = .048); neither GIP nor GIP(3-30)NH2 differed significantly from placebo in terms of postprandial glucose Cmax.
• In the post-exercise phase, the baseline-subtracted glucose area under the curve from 60 to 240 minutes after GIP infusion was lower than that after GIP(3-30)NH2 infusion (P = .008) but did not differ from that observed with placebo (P = .287).
• Minimum glucose levels and the amount or frequency of rescue glucose were comparable between the groups.
• No significant differences were observed in glucagon, insulin, C-peptide, or pancreatic polypeptide concentrations across the groups.

IN PRACTICE:

"Our findings suggest that supraphysiological levels of GIP do not protect against hypoglycaemia in T1 diabetes, consistent with the similar glucagon levels observed during GIP, the GIPR [GIP receptor] antagonist GIP(3-30)NH₂, and placebo infusions," the authors wrote.

SOURCE:

The study was led by Bjørn Hoe, MD, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. It was published online on December 28, 2025, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

All participants experienced hypoglycaemia, but variability in its timing and severity complicated the interpretation of results. The study may have been underpowered. The lack of detectable changes in insulin, C-peptide, and glucagon levels raised questions about whether GIP stabilizes plasma glucose independently of its effects on the endocrine pancreas.

DISCLOSURES:

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Some authors disclosed minority shareholdings, stock ownership, service on scientific advisory panels, receipt of honoraria as consultants or speakers, research support, and/or employment with pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.