Glucose-dependent insulinotropic polypeptide (GIP) is one of the key incretin hormones involved in glucose metabolism. Alongside glucagon-like peptide-1 (GLP-1), GIP plays a role in stimulating insulin secretion in response to nutrient intake. While incretin-based therapies have transformed the management of type 2 diabetes, their role in type 1 diabetes (T1D) remains less clear. Recent research has explored whether GIP could help mitigate postprandial glucose excursions or reduce the risk of hypoglycaemia in people with T1D, particularly in challenging real-world scenarios such as excess insulin dosing combined with physical activity.

Study Overview

In a controlled clinical study involving men with type 1 diabetes, researchers investigated the metabolic effects of an intravenous infusion of GIP under conditions designed to provoke hypoglycaemia. Participants received prandial insulin in excess of their physiological needs, followed by postmeal physical activity—a combination known to substantially increase the risk of low blood glucose levels.

To better understand GIP’s role, outcomes during GIP infusion were compared with those observed during infusion of a GIP receptor antagonist, GIP(3-30)NH₂. This antagonist blocks GIP receptor signaling and therefore serves as a useful comparator to isolate the hormone’s effects.

Effects on Hypoglycaemia

The primary finding of the study was that intravenous GIP infusion did not prevent hypoglycaemia in this high-risk setting. When prandial insulin doses were excessive and participants engaged in physical activity after eating, hypoglycaemic episodes still occurred despite the presence of GIP.

This result suggests that, in people with T1D, GIP alone is insufficient to counteract the powerful glucose-lowering effects of exogenous insulin combined with exercise. Unlike individuals with preserved endogenous insulin secretion, people with T1D lack the intrinsic beta-cell regulatory mechanisms that might otherwise allow incretin hormones to modulate insulin output in response to falling glucose levels.

Impact on Postprandial Glucose Peaks

Although GIP did not offer protection against hypoglycaemia, it did demonstrate a modest but measurable benefit in reducing postprandial glucose peaks. Compared with infusion of the GIP receptor antagonist, GIP infusion resulted in lower peak glucose concentrations after meals.

This finding indicates that GIP retains some glucose-lowering capacity in T1D, likely through mechanisms such as delayed gastric emptying, modulation of glucagon secretion, or enhanced peripheral glucose handling. However, the magnitude of this effect was limited and did not translate into improved safety in situations involving excessive insulin exposure.

Clinical Implications

The results highlight the complexity of glucose regulation in type 1 diabetes and underscore the limitations of incretin-based strategies in this population. While GIP may help smooth postprandial glucose excursions to a small extent, it does not appear to provide meaningful protection against hypoglycaemia during periods of insulin excess and physical exertion.

From a clinical perspective, these findings suggest that GIP-based therapies alone are unlikely to reduce hypoglycaemia risk in T1D. Careful insulin dose adjustment, continuous glucose monitoring, and individualized exercise planning remain the cornerstone strategies for preventing low blood glucose events.

Future Directions

Further research is needed to determine whether GIP could play a supportive role when combined with other hormonal or technological interventions, such as dual incretin agonists, closed-loop insulin delivery systems, or glucagon co-administration. Understanding how incretin hormones interact with exercise and exogenous insulin may help refine future therapies aimed at improving postprandial control without increasing hypoglycaemia risk.

Conclusion

In men with type 1 diabetes, intravenous GIP infusion modestly reduces postmeal glucose peaks but does not prevent hypoglycaemia when prandial insulin is administered in excess and followed by physical activity. These findings reinforce the challenges of achieving stable glycaemic control in T1D and suggest that, while GIP has limited metabolic benefits, it cannot replace careful insulin management in high-risk scenarios.