Liraglutide decreases energy expenditure and does not affect the fat fraction of supraclavicular brown adipose tissue in patients with type 2 diabetes
Abstract
Background and aims Several studies have shown that glucagon-like peptide-1 (GLP-1) analogues can affect resting energy expenditure, and preclinical studies suggest that they may activate brown adipose tissue (BAT). The aim of the present study was to investigate the effect of treatment with liraglutide on energy metabolism and BAT fat fraction in patients with type 2 diabetes.Methods and results In a 26-week double-blind, placebo-controlled trial, 50 patients with type 2 diabetes were randomized to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after treatment for 4, 12 and 26 weeks, we assessed resting energy expenditure (REE) by indirect calorimetry. Furthermore, at baseline and after 26 weeks, we determined the fat fraction in the supraclavicular BAT depot using chemical-shift water-fat MRI at 3T. Liraglutide reduced REE after 4 weeks, which persisted after 12 weeks and tended to be present after 26 weeks (week 26 vs baseline: liraglutide -52 ± 128 kcal/day; P = 0.071, placebo +44 ± 144 kcal/day; P = 0.153, between group P = 0.057). Treatment with liraglutide for 26 weeks did not decrease the fat fraction in supraclavicular BAT (-0.4 ± 1.7%; P = 0.447) compared to placebo (-0.4 ± 1.4%; P = 0.420; between group P = 0.911).Conclusion Treatment with liraglutide decreases REE in the first 12 weeks and tends to decrease this after 26 weeks without affecting the fat fraction in the supraclavicular BAT depot. These findings suggest reduction in energy intake rather than an increase in REE to contribute to the liraglutide-induced weight loss.Trial registry number NCT01761318.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A plausible explanation for the decline in REE following 4 weeks of liraglutide therapy could be that REE attenuates weight loss by adapting to improve metabolic efficiency in response to decreased food intake.
“Therefore, even after accounting for lean body mass, a plausible explanation for the decline in REE following 4 weeks of liraglutide therapy could be that REE attenuates weight loss by adapting to improve metabolic efficiency in response to decreased food intake [99].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [99]
Lean body mass reduction was documented in both human BAT studies, with fat-free mass being a significant component of REE.
“Remarkably, lean body mass reduction was documented in both studies, with fat-free mass being a significant component of REE.”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [99]
In humans, liraglutide treatment compared to placebo for 26 weeks produced no significant reduction in the supraclavicular fat fraction.
“When liraglutide treatment was compared to a placebo for 26 weeks, there was no significant reduction in the supraclavicular fat fraction.”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [99]
Cites
Friedewald, W. T., Levy, R. I., & Fredrickson, D. S. (1972) · Clinical Chemistry · doi:10.1093/clinchem/18.6.499 · Cited by 32,423 · see citing works
Turner, R. C., Fox, C., Matthews, McElroy, H. H., Cull, C. A., Holman, R. R., Neil, P., Hadden, D. R., Wright, D., Manley, E., et al. (1998) · The Lancet · Cited by 8,419 · see citing works
Identification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399 · see citing works
Zhou, B., Lu, Y., Hajifathalian, K., Bentham, J., Di Cesare, M., Danaei, G., Bixby, H., Cowan, M., Ali, M., Taddei, C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00618-8 · Cited by 4,311 · see citing works
Cold-Activated Brown Adipose Tissue in Healthy Men
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M. A. F. L., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808718 · Cited by 3,452 · see citing works
Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058 · see citing works
Glucagon-like peptide-1 7–36: a physiological incretin in man
Kreymann, B., Ghatei, M. A., Williams, G., & Bloom, S. R. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91194-9 · Cited by 1,928 · see citing works
Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans.
Flint, A., Raben, A., Astrup, A., & Holst, J. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci990 · Cited by 1,402 · see citing works
Davies, M. J., Bergenstal, R., Bode, B., Kushner, R. F., Lewin, A., Skjøth, T. V., Andreasen, A. H., Jensen, C. B., DeFronzo, R. A., & for the NN8022-1922 Study Group (2015) · JAMA · doi:10.1001/jama.2015.9676 · Cited by 1,198 · see citing works
Ouellet, V., Labbé, S. M., Blondin, D. P., Phoenix, S., Guérin, B., Haman, F., Turcotte, É. E., Richard, D., & Carpentier, A. C. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60433 · Cited by 985 · see citing works
on behalf of the NN8022-1807 Investigators, Astrup, A., Carraro, R., Finer, N., Harper, A., Kunesova, M., Lean, M. E. J., Niskanen, L., Rasmussen, M. F., Rissanen, A., et al. (2012) · International Journal of Obesity · doi:10.1038/ijo.2011.158 · Cited by 757 · see citing works
Zingaretti, M. C., Crosta, F., Vitali, A., Guerrieri, M., Frontini, A., Cannon, B., Nedergaard, J., & Cinti, S. (2009) · The FASEB Journal · doi:10.1096/fj.09-133546 · Cited by 725 · see citing works
Reeder, S. B., Pineda, A. R., Wen, Z., Shimakawa, A. S., Yu, H., Brittain, J. H., Gold, G. E., Beaulieu, C. F., & Pelc, N. J. (2005) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20624 · Cited by 707 · see citing works
GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK
Beiroa, D., Imbernon, M., Gallego, R., Senra, A., Herranz, D., Villarroya, F., Serrano, M., Fernø, J., Salvador, J., Escalada, J., et al. (2014) · Diabetes · doi:10.2337/db14-0302 · Cited by 602 · see citing works
Insulin‐associated weight gain in diabetes – causes, effects and coping strategies
Russell-Jones, D. L., & Khan, R. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00686.x · Cited by 556 · see citing works
van 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 · see citing works
Gutzwiller, J., Drewe, J., Göke, B., Schmidt, H., Rohrer, B., Lareida, J., & Beglinger, C. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1541 · Cited by 521 · see citing works
Multicoil Dixon chemical species separation with an iterative least‐squares estimation method
Reeder, S. B., Wen, Z., Yu, H., Pineda, A. R., Gold, G. E., Markl, M., & Pelc, N. J. (2003) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10675 · Cited by 508 · see citing works
Limitations in the assessment of dietary energy intake by self-report
Schoeller, D. A. (1995) · Metabolism · doi:10.1016/0026-0495(95)90204-x · Cited by 496 · see citing works
Multiecho reconstruction for simultaneous water‐fat decomposition and T2* estimation
Yu, H., McKenzie, C. A., Shimakawa, A. S., Vu, A. T., Brau, A. C. S., Beatty, P. J., Pineda, A. R., Brittain, J. H., & Reeder, S. B. (2007) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21090 · Cited by 437 · see citing works
Brown fat fuel utilization and thermogenesis
Townsend, K. L., & Tseng, Y. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.004 · Cited by 331 · see citing works
Lee, P., Greenfield, J. R., Ho, K. K. Y., & FULHAM, M. J. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00298.2010 · Cited by 314 · see citing works
Brown Adipose Tissue and Seasonal Variation in Humans
Au-Yong, I. T. H., Thorn, N., Ganatra, R. H., Perkins, A. C., & Symonds, M. E. (2009) · Diabetes · doi:10.2337/db09-0833 · Cited by 270 · see citing works
Energy expenditure and postprandial thermogenesis in obese women before and after weight loss
Bessard, T., Schutz, Y., & Jéquier, E. (1983) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/38.5.680 · Cited by 257 · see citing works
Glucagonlike peptide 1: a newly discovered gastrointestinal hormone
Holst, J. J. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90831-1 · Cited by 252 · see citing works
Harder, H., Nielsen, L., Thi, T. D. T., & Astrup, A. V. (2004) · Diabetes Care · doi:10.2337/diacare.27.8.1915 · Cited by 232 · see citing works
Blonde, L., & Russell-Jones, D. L. (2009) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2009.01075.x · Cited by 227 · see citing works
Field map estimation with a region growing scheme for iterative 3‐point water‐fat decomposition
Yu, H., Reeder, S. B., Shimakawa, A. S., Brittain, J. H., & Pelc, N. J. (2005) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20654 · Cited by 217 · see citing works
Horowitz, M., Flint, A., Jones, K. L., Hindsberger, C., Rasmussen, M. F., Kapitza, C., Doran, S., Jax, T., Zdravkovic, M., & Chapman, I. M. (2012) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2012.02.016 · Cited by 179 · see citing works
Kooijman, S., Wang, Y., Parlevliet, E. T., Boon, M. R., Edelschaap, D., Snaterse, G., Pijl, H., Romijn, J. A., & Rensen, P. C. N. (2015) · Diabetologia · doi:10.1007/s00125-015-3727-0 · Cited by 140 · see citing works
Self-citationMR properties of brown and white adipose tissues
Hamilton, G., Smith, D. L., Bydder, M., Nayak, K. S., & Hu, P. (2011) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.22623 · Cited by 123 · see citing works
Hu, P., Yin, L., Aggabao, P. C., Perkins, T. G., Chia, J. M., & Gilsanz, V. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24053 · Cited by 93 · see citing works
Prediction of energy requirements of obese patients after massive weight loss.
Doré, C. J., Hesp, R., Wilkins, D., & Garrow, J. S. (1982) · PubMed · Cited by 70 · see citing works
Brown Adipose Tissue Quantification in Human Neonates Using Water-Fat Separated MRI
Rasmussen, J. M., Entringer, S., Nguyen, A., van Erp, T. G. M., Guijarro, A. I., Oveisi, F., Swanson, J. M., Piomelli, D., Wadhwa, P. D., Buß, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077907 · Cited by 66 · see citing works
Kiortsis, D. N., Durack, I., & Turpin, G. (1999) · European Journal of Pediatrics · doi:10.1007/s004310051117 · Cited by 59 · see citing works
Barrows, K. K., & Snook, J. (1987) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/45.2.391 · Cited by 57 · see citing works
Franssens, B. T., Hoogduin, H. M., Leiner, T., van der Graaf, Y., & Visseren, F. L. J. (2017) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.25594 · Cited by 54 · see citing works
Stahl, V., Maier, F. C., Freitag, M. T., Floca, R. O., Berger, M. C., Umathum, R., Díaz, M. B., Herzig, S., Weber, M. D., Dimitrakopoulou‐Strauss, A., et al. (2016) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.25364 · Cited by 41 · see citing works
Holstila, M., Virtanen, K. A., Grönroos, T. J., et al. (2013) · Metabolism · doi:10.1016/j.metabol.2013.03.002 · Cited by 40 · see citing works
Wu, C., Cheng, W., Sun, Y., Dang, Y., Gong, F., Zhu, H., Li, N., Li, F., & Zhu, Z. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113742 · Cited by 39 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
GLP-1 physiology informs the pharmacotherapy of obesity
Drucker, D. J. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101351 · Cited by 510 · see citing works
Karakasis, P., Patoulias, D., Fragakis, N., & Mantzoros, C. S. (2025) · Metabolism · doi:10.1016/j.metabol.2024.156113 · Cited by 242 · see citing works
Vosoughi, K., Atieh, J., Khanna, L., Khoshbin, K., Prokop, L. J., Davitkov, P., Murad, M. H., & Camilleri, M. (2021) · eClinicalMedicine · doi:10.1016/j.eclinm.2021.101213 · Cited by 97 · see citing works
Vosoughi, K., Salman Roghani, R., & Camilleri, M. (2022) · Obesity Medicine · doi:10.1016/j.obmed.2022.100456 · Cited by 65 · see citing works
Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
Conceição-Furber, E., Coskun, T., Sloop, K. W., & Samms, R. J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.868037 · Cited by 48 · see citing works
Hropot, T., Herman, R., Janez, A., Lezaic, L., & Jensterle, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108592 · Cited by 39 · see citing works
The effect of obesity pharmacotherapy on body composition, including muscle mass
Argyrakopoulou, G., Gitsi, E., Konstantinidou, S. K., & Kokkinos, A. (2025) · International Journal of Obesity · doi:10.1038/s41366-024-01533-3 · Cited by 28 · see citing works
De Fano, M., Malara, M., Vermigli, C., & Murdolo, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168650 · Cited by 17 · see citing works
Yates, T., Sargeant, J. A., King, J. A., Henson, J., Edwardson, C. L., Redman, E., Gulsin, G. S., Brady, E. M., Ahmad, E., Stensel, D. J., et al. (2022) · Diabetes Care · doi:10.2337/dc22-0888 · Cited by 9 · see citing works
- Authors
- van Eyk, H. J., Paiman, E. H. M., Bizino, M. B., IJzermans, S. L., Kleiburg, F., Boers, T. G. W., Rappel, E. J., Burakiewicz, J., Kan, H. E., Smit, J. W. A., Lamb, H. J., Jazet, I. M., & Rensen, P. C. N.
- Affiliations
- Leiden University Medical Center (NL)
- Radboud University Medical Center (NL)
- ORCID
- Venue
- Nutrition, Metabolism and Cardiovascular Diseases
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 30
- Issue
- 4
- Pages
- 616-624
- ISSN
- 0939-4753 (ISSN-L)
- OpenAlex
- W2996481440
- Cited by
- 54
- References
- 41
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 11 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 3
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutrition Metabolism and Cardiovascular Diseases (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Novo Nordisk A/S
- European Union’s Seventh Framework Programme for research, technological development and demonstration (602485)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- liraglutide, type 2 diabetes, resting energy expenditure, brown adipose tissue, fat fraction, GLP-1 receptor agonists, weight loss mechanisms, energy metabolism
- MeSH terms
- Liraglutide, Aged, Adipose Tissue, Brown, Diabetes Mellitus, Type 2, Double-Blind Method, Energy Metabolism, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Netherlands, Prospective Studies, Time Factors, Weight Loss, Treatment Outcome, Adiposity, Incretins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
