Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes
| Autor: | Charlotte C van Ruiten, Dick J Veltman, Anouk Schrantee, Liselotte van Bloemendaal, Frederik Barkhof, Mark H H Kramer, Max Nieuwdorp, Richard G IJzerman |
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| Přispěvatelé: | Internal medicine, ACS - Diabetes & metabolism, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Radiology and nuclear medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, AGEM - Endocrinology, metabolism and nutrition, Amsterdam Gastroenterology Endocrinology Metabolism, Radiology and Nuclear Medicine, APH - Personalized Medicine, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Experimental Vascular Medicine, Vascular Medicine, APH - Mental Health |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Blood Glucose
obesity GLP-1 receptor agonist Endocrinology Diabetes and Metabolism exenatide Clinical Biochemistry functional neuroimaging Biochemistry body weight Endocrinology Double-Blind Method Glucosides Weight Loss satiety and reward circuits Humans Hypoglycemic Agents Benzhydryl Compounds Sodium-Glucose Transporter 2 Inhibitors Glycated Hemoglobin Biochemistry (medical) Brain SGLT2 inhibitor dapagliflozin Middle Aged central nervous system Diabetes Mellitus Type 2 type 2 diabetes Cues |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism, 107(6), E2590-E2599. The Endocrine Society van Ruiten, C C, Veltman, D J, Schrantee, A, van Bloemendaal, L, Barkhof, F, Kramer, M H H, Nieuwdorp, M & Ijzerman, R G 2022, ' Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes ', Journal of Clinical Endocrinology and Metabolism, vol. 107, no. 6, pp. E2590-E2599 . https://doi.org/10.1210/clinem/dgac043 Journal of clinical endocrinology and metabolism, 107(6), E2590-E2599. The Endocrine Society |
| ISSN: | 0021-972X |
| DOI: | 10.1210/clinem/dgac043 |
| Popis: | Context Sodium-glucose cotransporter-2 inhibitors (SGLT2i) cause less weight loss than expected based on urinary calorie excretion. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, leading to increased appetite and food intake. Glucagon-like peptide-1 receptor agonists are associated with reduced appetite and body weight, mediated by direct and indirect central nervous system (CNS) effects. Objective We investigated the separate and combined effects of dapagliflozin and exenatide on the CNS in participants with obesity and type 2 diabetes. Methods This was a 16-week, double-blind, randomized, placebo-controlled trial. Obese participants with type 2 diabetes (n = 64, age 63.5 ± 0.9 years, BMI 31.7 ± 0.6 kg/m2) were randomized (1:1:1:1) to dapagliflozin 10 mg with exenatide-matched placebo, exenatide twice daily 10 µg with dapagliflozin-matched placebo, dapagliflozin and exenatide, or double placebo. Using functional MRI, the effects of treatments on CNS responses to viewing food pictures were assessed after 10 days and 16 weeks of treatment. Results After 10 days, dapagliflozin increased, whereas exenatide decreased CNS activation in the left putamen. Combination therapy had no effect on responses to food pictures. After 16 weeks, no changes in CNS activation were observed with dapagliflozin, but CNS activation was reduced with dapagliflozin-exenatide in right amygdala. Conclusion The early increase in CNS activation with dapagliflozin may contribute to the discrepancy between observed and expected weight loss. In combination therapy, exenatide blunted the increased CNS activation observed with dapagliflozin. These findings provide further insights into the weight-lowering mechanisms of SGLT2i and GLP-1 receptor agonists. |
| Databáze: | OpenAIRE |
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