No Acute Effects of Exogenous Glucose-Dependent Insulinotropic Polypeptide on Energy Intake, Appetite, or Energy Expenditure When Added to Treatment With a Long-Acting Glucagon-Like Peptide 1 Receptor Agonist in Men With Type 2 Diabetes

Objective: Dual incretin receptor agonists in clinical development have shown reductions in body weight and hemoglobin A (HbA) in patients with type 2 diabetes, but the impact of glucose-dependent insulinotropic polypeptide (GIP) receptor activation remains unclear. Here, we evaluated the effects of high-dose exogenous GIP on energy intake, energy expenditure, plasma glucose, and glucose-regulating hormones in patients with type 2 diabetes treated with a long-acting glucagon-like peptide 1 receptor (GLP-1R) agonist.

Research Design And Methods: In a randomized, double-blind design, men with type 2 diabetes ( = 22, mean ± SEM HbA 6.8 ± 0.1% [51 ± 1.5 mmol/mol]) treated with metformin and long-acting GLP-1R agonists were subjected to two 5-h continuous infusions (separated by a washout period of ≥3 days): one with GIP (6 pmol/kg/min) and another with saline (placebo). After 60 min of infusion, a liquid mixed-meal test was performed, and after 270 min of infusion, an ad libitum meal was served for evaluation of energy intake (primary end point).

Results: Energy intake was similar during GIP and placebo infusion (648 ± 74 kcal vs. 594 ± 55 kcal, respectively; = 0.480), as were appetite measures and energy expenditure. Plasma glucagon and glucose were higher during GIP infusion compared with placebo infusion ( = 0.026 and = 0.017) as assessed by area under the curve.

Conclusions: In patients with type 2 diabetes, GIP infusion on top of treatment with metformin and a long-acting GLP-1R agonist did not affect energy intake, appetite, or energy expenditure but increased plasma glucose compared with placebo. These results indicate no acute beneficial effects of combining GIP and GLP-1.