Natasha C Bergmann1,2,3, Lærke S Gasbjerg1,3, Sebastian M Heimbürger1,4, Liva S L Krogh1, Flemming Dela5,6, Bolette Hartmann3,4, Jens J Holst3,4, Lene Jessen2, Mikkel B Christensen1,7,8, Tina Vilsbøll1,7,9, Asger Lund1, Filip K Knop10,4,7,9. 1. Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. 2. Zealand Pharma A/S, Glostrup, Denmark. 3. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 5. Xlab, Center for Healthy Ageing, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Department of Geriatrics, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. 7. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 8. Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. 9. Steno Diabetes Center Copenhagen, Gentofte, Denmark. 10. Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark filip.krag.knop.01@regionh.dk.
Abstract
OBJECTIVE: Dual incretin receptor agonists in clinical development have shown reductions in body weight and hemoglobin A1c (HbA1c) 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 = 22, mean ± SEMHbA1c 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; P = 0.480), as were appetite measures and energy expenditure. Plasma glucagon and glucose were higher during GIP infusion compared with placebo infusion (P = 0.026 and P = 0.017) as assessed by area under the curve. CONCLUSIONS: In patients with type 2 diabetes, GIP infusion on top of treatment withmetformin 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.
RCT Entities:
OBJECTIVE: Dual incretin receptor agonists in clinical development have shown reductions in body weight and hemoglobin A1c (HbA1c) 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 = 22, mean ± SEM HbA1c 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; P = 0.480), as were appetite measures and energy expenditure. Plasma glucagon and glucose were higher during GIP infusion compared with placebo infusion (P = 0.026 and P = 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.
Authors: Sebastian M N Heimbürger; Bjørn Hoe; Chris N Nielsen; Natasha C Bergmann; Bolette Hartmann; Jens J Holst; Tina Vilsbøll; Thomas F Dejgaard; Mikkel B Christensen; Filip K Knop Journal: Diabetologia Date: 2021-08-17 Impact factor: 10.122
Authors: Francis S Willard; Jonathan D Douros; Maria Bn Gabe; Aaron D Showalter; David B Wainscott; Todd M Suter; Megan E Capozzi; Wijnand Jc van der Velden; Cynthia Stutsman; Guemalli R Cardona; Shweta Urva; Paul J Emmerson; Jens J Holst; David A D'Alessio; Matthew P Coghlan; Mette M Rosenkilde; Jonathan E Campbell; Kyle W Sloop Journal: JCI Insight Date: 2020-09-03