TY - JOUR
T1 - Brain Activation in Response to Low-Calorie Food Pictures
T2 - An Explorative Analysis of a Randomized Trial With Dapagliflozin and Exenatide
AU - van Ruiten, Charlotte C.
AU - Veltman, Dick J.
AU - Nieuwdorp, Max
AU - IJzerman, Richard G.
N1 - Funding Information: The authors thank Ton Schweigmann (Department of Radiology and Nuclear Medicine, VU University Medical Center), Renée de Meijer, Jeanette Boerop, and Ingrid Knuffman for their assistance during the test visits, as well as the participants who participated in this study. Funding Information: RI is principal investigator of studies sponsored by research grants from AstraZeneca, Eli Lilly & Co., and Novo Nordisk. MN is supported by a personal ZONMW VICI grant 2020 (09150182010020) and received an unrestricted grant from AstraZeneca and serves on the Scientific Advisory Board of Caelus Pharmaceuticals, the Netherlands, and Kaleido, USA. All authors declare they have not received any fees personally in connection with the roles described above, as all honoraria were paid to their employer (Amsterdam University Medical Centers, location VUmc). None of these potential conflicts of interest are relevant to this article. Funding Information: This work was funded by an investigator initiated grant from AstraZeneca (ESR-16-11865). The funder had no role in the study design, data analyses or interpretation, or drafting of the manuscript, nor in the decision to submit the manuscript for publication. Publisher Copyright: Copyright © 2022 van Ruiten, Veltman, Nieuwdorp and IJzerman.
PY - 2022/5/4
Y1 - 2022/5/4
N2 - Background and Aim: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce less weight loss than expected. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, contributing to increased appetite and food intake. This hyperphagia may be specific to high-calorie foods. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with lower preferences for high-calorie foods, and with decreased activation in areas regulating satiety and reward in response to high-calorie food pictures, which may reflect this lower preference for energy-dense foods. To optimize treatment, we need a better understanding of how intake is controlled, and how [(un)healthy] food choices are made. The aim of the study was to investigate the effects of dapagliflozin, exenatide, and their combination on brain activation in response to low-calorie food pictures. Methods: We performed an exploratory analysis of a larger, 16-week, double-blind, randomized, placebo-controlled trial. Sixty-eight subjects with obesity and type 2 diabetes were randomized to dapagliflozin, exenatide, dapagliflozin plus exenatide, or double placebo. Using functional MRI, the effects of treatments on brain responses to low-calorie food pictures were assessed after 10 days and 16 weeks. Results: Dapagliflozin versus placebo decreased activity in response to low-calorie food pictures, in the caudate nucleus, insula, and amygdala after 10 days, and in the insula after 16 weeks. Exenatide versus placebo increased activation in the putamen in response to low-calorie food pictures after 10 days, but not after 16 weeks. Dapagliflozin plus exenatide versus placebo had no effect on brain responses, but after 10 days dapagliflozin plus exenatide versus dapagliflozin increased activity in the insula and amygdala in response to low-calorie food pictures. Conclusion: Dapagliflozin decreased activation in response to low-calorie food pictures, which may reflect a specific decreased preference for low-calorie foods, in combination with the previously found increased activation in response to high-calorie foods, which may reflect a specific preference for high-calorie foods, and may hamper SGLT2i-induced weight loss. Exenatide treatment increased activation in response to low-calorie foods. Combination treatment may lead to more favorable brain responses to low-calorie food cues, as we observed that the dapagliflozin-induced decreased response to low-calorie food pictures had disappeared.
AB - Background and Aim: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce less weight loss than expected. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, contributing to increased appetite and food intake. This hyperphagia may be specific to high-calorie foods. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with lower preferences for high-calorie foods, and with decreased activation in areas regulating satiety and reward in response to high-calorie food pictures, which may reflect this lower preference for energy-dense foods. To optimize treatment, we need a better understanding of how intake is controlled, and how [(un)healthy] food choices are made. The aim of the study was to investigate the effects of dapagliflozin, exenatide, and their combination on brain activation in response to low-calorie food pictures. Methods: We performed an exploratory analysis of a larger, 16-week, double-blind, randomized, placebo-controlled trial. Sixty-eight subjects with obesity and type 2 diabetes were randomized to dapagliflozin, exenatide, dapagliflozin plus exenatide, or double placebo. Using functional MRI, the effects of treatments on brain responses to low-calorie food pictures were assessed after 10 days and 16 weeks. Results: Dapagliflozin versus placebo decreased activity in response to low-calorie food pictures, in the caudate nucleus, insula, and amygdala after 10 days, and in the insula after 16 weeks. Exenatide versus placebo increased activation in the putamen in response to low-calorie food pictures after 10 days, but not after 16 weeks. Dapagliflozin plus exenatide versus placebo had no effect on brain responses, but after 10 days dapagliflozin plus exenatide versus dapagliflozin increased activity in the insula and amygdala in response to low-calorie food pictures. Conclusion: Dapagliflozin decreased activation in response to low-calorie food pictures, which may reflect a specific decreased preference for low-calorie foods, in combination with the previously found increased activation in response to high-calorie foods, which may reflect a specific preference for high-calorie foods, and may hamper SGLT2i-induced weight loss. Exenatide treatment increased activation in response to low-calorie foods. Combination treatment may lead to more favorable brain responses to low-calorie food cues, as we observed that the dapagliflozin-induced decreased response to low-calorie food pictures had disappeared.
KW - GLP-1 receptor agonist
KW - SGLT2 inhibitor
KW - central regulation of food intake
KW - dapagliflozin
KW - exenatide
KW - functional neuroimaging
KW - low-calorie
KW - obesity
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85130539473&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fendo.2022.863592
DO - https://doi.org/10.3389/fendo.2022.863592
M3 - Article
C2 - 35600575
SN - 1664-2392
VL - 13
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
M1 - 863592
ER -