Liraglutide Reduces CNS Activation in Response to Visual Food Cues Only After Short-term Treatment in Patients With Type 2 Diabetes
Open accessAbstract
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with reduced appetite and body weight. We investigated whether these effects could be mediated by the central nervous system (CNS). RESEARCH DESIGN AND METHODS: We performed a randomized crossover study in obese patients with type 2 diabetes (n = 20, mean age 59.3 ± 4.1 years, mean BMI 32 ± 4.7 kg/m2), consisting of two periods of 12-week treatment with either liraglutide 1.8 mg or insulin glargine. Using functional MRI, we determined the effects of treatment on CNS responses to viewing food pictures in the fasted condition and 30 min after meal intake. RESULTS: After 12 weeks, the decrease in HbA1c was larger with liraglutide versus insulin glargine (Δ−0.7% vs. −0.2%, P < 0.001). Body weight decreased during liraglutide versus insulin glargine (Δ−3.3 kg vs. 0.8 kg, P < 0.001). After 10 days, patients treated with liraglutide, compared with insulin glargine, showed decreased responses to food pictures in insula and putamen (P ≤ 0.02). In addition, liraglutide enhanced the satiating effect of meal intake on responses in putamen and amygdala (P ≤ 0.05). Differences between liraglutide and insulin glargine were not observed after 12 weeks. CONCLUSIONS: Compared with insulin, liraglutide decreased CNS activation significantly only after short-term treatment, suggesting that these effects of GLP-1RA on the CNS may contribute to the induction of weight loss, but not necessarily to its maintenance, in view of the absence of an effect of liraglutide on CNS activation in response to food pictures after longer-term treatment.
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Doxazosin increases heart rate by ~25% and is associated with an increase in heart failure incidence compared with chlorthalidone.
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Cites
Stratton, I. M. (2000) · BMJ · doi:10.1136/bmj.321.7258.405 · Cited by 9,059 · see citing works
Dissociable Roles of Ventral and Dorsal Striatum in Instrumental Conditioning
O'Doherty, J., Dayan, P., Schultz, J., Deichmann, R., Friston, K., & Dolan, R. J. (2004) · Science · doi:10.1126/science.1094285 · Cited by 2,088 · see citing works
Baxter, M. G., & Murray, E. A. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn875 · Cited by 1,200 · see citing works
Nauck, M., Frid, A., Hermansen, K., Shah, N. S., Tankova, T., Mitha, I. H., Zdravkovic, M., Düring, M., Matthews, D. R., & for the LEAD-2 Study Group (2009) · Diabetes Care · doi:10.2337/dc08-1355 · Cited by 1,129 · see citing works
Vilsboll, T., Christensen, M., Junker, A. E., Knop, F. K., & Gluud, L. L. (2012) · BMJ · doi:10.1136/bmj.d7771 · Cited by 970 · see citing works
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss
Secher, A., Jelsing, J., Baquero, A. F., Hecksher-Sørensen, J., Cowley, M. A., Dalbøge, L. S., Hansen, G., Grove, K. L., Pyke, C., Raun, K., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75276 · Cited by 961 · see citing works
Widespread reward-system activation in obese women in response to pictures of high-calorie foods
Stoeckel, L. E., Weller, R. E., Cook, E. W., Twieg, D. B., Knowlton, R. C., & Cox, J. E. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.02.031 · Cited by 857 · see citing works
Rothemund, Y., Preuschhof, C., Bohner, G., Bauknecht, H.-C., Klingebiel, R., Flor, H., & Klapp, B. F. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.05.008 · Cited by 679 · cited 2× · see citing works
“, insula, striatum, amygdala, and orbitofrontal cortex) were determined based on previous studies (4,5,15).”
BackgroundMethodvan Can, J., Sloth, B., Jensen, C. B., Flint, A., Blaak, E. E., & Saris, W. H. M. (2014) · International Journal of Obesity · doi:10.1038/ijo.2013.162 · Cited by 537 · cited 1× · see citing works
“In a study in obese individuals (35), 5 weeks of treatment with 1.”
BackgroundHunter, K., & Hölscher, C. (2012) · BMC Neuroscience · doi:10.1186/1471-2202-13-33 · Cited by 504 · see citing works
Evidence that Intestinal Glucagon-Like Peptide-1 Plays a Physiological Role in Satiety
Williams, D. L., Baskin, D. G., & Schwartz, M. W. (2009) · Endocrinology · doi:10.1210/en.2008-1045 · Cited by 300 · see citing works
Circulating glucose levels modulate neural control of desire for high-calorie foods in humans
Page, K. A., Seo, D., Belfort-DeAguiar, R., Lacadie, C., Dzuira, J., Naik, S., Amarnath, S., Constable, R. T., Sherwin, R. S., & Sinha, R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57873 · Cited by 212 · see citing works
Initiate Insulin by Aggressive Titration and Education (INITIATE)
Yki-Järvinen, H., Juurinen, L., Alvarsson, M., Bystedt, T., Caldwell, I., Davies, M., Lahdenperä, S., Nijpels, G., & Vähätalo, M. (2007) · Diabetes Care · doi:10.2337/dc06-1357 · Cited by 139 · see citing works
Schirra, J., Wank, U., Arnold, R., Göke, B., & Katschinski, M. (2002) · Gut · doi:10.1136/gut.50.3.341 · Cited by 130 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868 · see citing works
Pharmacotherapy of obesity: an update on the available medications and drugs under investigation
Chakhtoura, M., Haber, R., Ghezzawi, M., Rhayem, C., Tcheroyan, R., & Mantzoros, C. S. (2023) · eClinicalMedicine · doi:10.1016/j.eclinm.2023.101882 · Cited by 462 · see citing works
GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes
Muskiet, M. H. A., Tonneijck, L., Smits, M. M., van Baar, M. J. B., Kramer, M. H. H., Hoorn, E. J., Joles, J. A., & van Raalte, D. H. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.123 · Cited by 407 · see citing works
Smits, M. M., & Van Raalte, D. H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.645563 · Cited by 332 · see citing works
Farr, O. M., Sofopoulos, M., Tsoukas, M. A., Dincer, F., Thakkar, B., Sahin-Efe, A., Filippaios, A., Bowers, J., Srnka, A., Gavrieli, A., et al. (2016) · Diabetologia · doi:10.1007/s00125-016-3874-y · Cited by 287 · see citing works
Pharmacotherapy of obesity: available medications and drugs under investigation.
Pilitsi, E., Farr, O. M., Polyzos, S. A., Perakakis, N., Nolen-Doerr, E., Papathanasiou, A.-E., & Mantzoros, C. S. (2019) · Metabolism · doi:10.1016/j.metabol.2018.10.010 · Cited by 248 · see citing works
Heuvelman, V. D., Van Raalte, D. H., & Smits, M. M. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvz323 · Cited by 106 · see citing works
Wium‐Andersen, I. K., Wium‐Andersen, M. K., Fink‐Jensen, A., Rungby, J., Jørgensen, M. B., & Osler, M. (2022) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13776 · Cited by 93 · see citing works
Glucagon-like peptide 1 agonist and effects on reward behaviour: A systematic review
Badulescu, S., Tabassum, A., Le, G. H., Wong, S., Phan, L., Gill, H., Llach, C.-D., McIntyre, R. S., Rosenblat, J., & Mansur, R. (2024) · Physiology & Behavior · doi:10.1016/j.physbeh.2024.114622 · Cited by 90 · see citing works
Costa, A., Ai, M., Nunn, N., Culotta, I., Hunter, J., Boudjadja, M. B., Valencia-Torres, L., Aviello, G., Hodson, D. J., Snider, B. M., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101407 · Cited by 79 · see citing works
Neural Predictors of 12-Month Weight Loss Outcomes Following Bariatric Surgery
Holsen, L. M., Davidson, P., Cerit, H., Hye, T., Moondra, P., Haimovici, F., Sogg, S., Shikora, S., Goldstein, J. M., Evins, A. E., et al. (2018) · International Journal of Obesity · doi:10.1038/ijo.2017.190 · Cited by 69 · see citing works
Farr, O. M., Upadhyay, J., Rutagengwa, C., DiPrisco, B., Ranta, Z., Adra, A., Bapatla, N., Douglas, V. P., Douglas, K. A. A., Nolen‐Doerr, E., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13827 · Cited by 64 · see citing works
Marrano, N., Biondi, G., Borrelli, A., Cignarelli, A., Perrini, S., Laviola, L., Giorgino, F., & Natalicchio, A. (2021) · Biomolecules · doi:10.3390/biom11020286 · Cited by 56 · see citing works
Bae, J. H., Choi, H. J., Cho, K. I. K., Kim, L. K., Kwon, J. S., & Cho, Y. M. (2020) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2019.0018 · Cited by 33 · see citing works
Yin, T.-T., Bi, Y., Li, P., Shen, S.-M., Wang, W.-M., Jiang, C., Gao, C.-X., Wang, Y., Gao, L.-J., Zhu, D.-L., et al. (2018) · Nutrition & Metabolism · doi:10.1186/s12986-018-0295-6 · Cited by 26 · see citing works
Do GLP-1 Receptor Agonists Alter Brain Responses to Reward-Related Cues? A Systematic Review
Dang, V., Sambuco, N., Yammine, L., & Versace, F. (2026) · doi:10.64898/2026.01.31.702984 · Cited by 4 · see citing works
- Authors
- ten Kulve, J. S., Veltman, D. J., van Bloemendaal, L., Barkhof, F., Drent, M. L., Diamant, M., & IJzerman, R. G.
- Affiliations
- Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Gemeente Amsterdam (NL)
- Vrije Universiteit Amsterdam (NL)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2015-08-17
- Volume
- 39
- Issue
- 2
- Pages
- 214-221
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W1536061722
- Cited by
- 102
- References
- 14
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 5 · 2023: 7 · 2022: 12 · 2021: 17 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 7
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- liraglutide, GLP-1 receptor agonists, type 2 diabetes, obesity, food cue reactivity, central nervous system activation, food images, insulin glargine, weight loss, satiety, insula, putamen, amygdala, functional MRI, HbA1c
- MeSH terms
- Insulin Glargine, Liraglutide, Blood Glucose, Body Weight, Brain, Cues, Diabetes Mellitus, Type 2, Fasting, Female, Food, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Obesity, Satiation, Cross-Over Studies, Glucagon-Like Peptide 1
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