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

41 Citations (Scopus)

Abstract

OBJECTIVE Dual incretin receptor agonists in clinical development have shown reductions in body weight and hemoglobin A 1c (HbA 1c) 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 (n 5 22, mean 6 SEM HbA 1c 6.8 6 0.1% [51 6 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 6 74 kcal vs. 594 6 55 kcal, respectively; P 5 0.480), as were appetite measures and energy expenditure. Plasma glucagon and glucose were higher during GIP infusion compared with placebo infusion (P 5 0.026 and P 5 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.

Original languageEnglish
Article numberdc190578
JournalDiabetes Care
Volume43
Issue number3
Pages (from-to)588-596
Number of pages9
ISSN1935-5548
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Adult
  • Aged
  • Appetite/drug effects
  • Delayed-Action Preparations/administration & dosage
  • Diabetes Mellitus, Type 2/drug therapy
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Energy Intake/drug effects
  • Energy Metabolism/drug effects
  • Gastric Inhibitory Polypeptide/administration & dosage
  • Glucagon-Like Peptide 1/administration & dosage
  • Glucagon-Like Peptide-1 Receptor/agonists
  • Glucagon/blood
  • Glycated Hemoglobin A/drug effects
  • Humans
  • Insulin/blood
  • Male
  • Middle Aged

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