Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist

Iepsen, Eva W.; Zhang, Jinyi; Thomsen, Henrik S.; Hansen, Elizaveta L.; Hollensted, Mette; Madsbad, Sten; Hansen, Torben; Holst, Jens J.; Holm, Jens-Christian; Torekov, Signe S.

doi:10.1016/j.cmet.2018.05.008

Cited by 156Regulation of Appetite and ObesityPharmacology and Obesity TreatmentDiabetes Treatment and Management

Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist

Open access

Iepsen, Eva W., Zhang, Jinyi, Thomsen, Henrik S., Hansen, Elizaveta L., Hollensted, Mette, Madsbad, Sten, Hansen, Torben, Holst, Jens J. +2 more·2018·Cell Metabolism

DOI 10.1016/j.cmet.2018.05.008

Open this paper in CoChat — free account Open PDF

Abstract

Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2018.05.008

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Liraglutide, a GLP-1 receptor agonist, is used in the treatment of obesity because it induces weight loss and maintains low-calorie diet-induced weight loss for at least 1 year, primarily by means of appetite inhibition.
“Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used in the treatment of obesity because it induces weight loss 21-23 and maintains low-calorie diet-induced weight loss for at least 1 year, 11,24 primarily by means of appetite inhibition. 25”
From Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined (2021) · cites this paper as [23]
Short-term studies have demonstrated that GLP-1 receptor agonists induce weight loss by promoting satiety and reducing hunger.
“Short-term studies have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RA) induce weight loss by promoting satiety and reducing hunger16–19.”
From Exploratory analysis of eating-and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment (2022) · cites this paper as [19]
Evidence from a small clinical study with liraglutide suggests that GLP-1 receptor agonists may be effective in people with MC4R deficiency.
“there is evidence from a small clinical study with liraglutide20 that they may be effective in people with MC4R deficiency.”
From Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency (2025) · cites this paper as [20]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629 · see citing works
Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Use and Abuse of HOMA Modeling
Wallace, T. M., Levy, J. C., & Matthews, D. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.6.1487 · Cited by 5,114 · see citing works
Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies
Prospective Studies Collaboration (2009) · The Lancet · doi:10.1016/s0140-6736(09)60318-4 · Cited by 4,807 · see citing works
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030 · see citing works
A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C. W., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411892 · Cited by 2,724 · see citing works
Body-mass index and mortality among 1.46 million white adults
Berrington de Gonzalez, A., Hartge, P., Cerhan, J. R., Flint, A. J., Hannan, L., MacInnis, R. J., Moore, S. C., Tobias, G. S., Anton-Culver, H., Freeman, L. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000367 · Cited by 2,317 · see citing works
Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study
Armstrong, M. J., Gaunt, P., Aithal, G. P., Barton, D., Hull, D., Parker, R., Hazlehurst, J. M., Guo, K., Abouda, G., Aldersley, M. A., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00803-x · Cited by 2,203 · see citing works
Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
Farooqi, I. S., Keogh, J. M., Yeo, G. S. H., Lank, E. J., Cheetham, T., & O'Rahilly, S. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022050 · Cited by 1,778 · 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
Self-citation
Effects of liraglutide in the treatment of obesity: A randomised, double-blind, placebo-controlled study
Astrup, A., Rössner, S., Van Gaal, L., Rissanen, A., Niskanen, L., Al Hakim, M., Madsen, J., Rasmussen, M. F., & Lean, M. E. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61375-1 · Cited by 1,163 · see citing works
From Lesions to Leptin
Elmquist, J. K., Elias, C. F., & Saper, C. B. (1999) · Neuron · doi:10.1016/s0896-6273(00)81084-3 · Cited by 1,160 · see citing works
Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain
Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., & Cone, R. D. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.10.7854347 · Cited by 1,157 · see citing works
Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in Type 2 (non-insulin-dependent) diabetic patients
Nauck, M. A., Kleine, N., �rskov, C., Holst, J. J., Willms, B., & Creutzfeldt, W. (1993) · Diabetologia · doi:10.1007/bf00401145 · Cited by 1,092 · see citing works
Self-citation
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
Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity
Vaisse, C., Clement, K., Durand, E., Hercberg, S., Guy-Grand, B., & Froguel, P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9238 · Cited by 897 · see citing works
Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance Randomized Study
on behalf of the NN8022-1923 Investigators, Wadden, T. A., Hollander, P., Klein, S., Niswender, K., Woo, V, Hale, P. M., & Aronne, L. (2013) · International Journal of Obesity · doi:10.1038/ijo.2013.120 · Cited by 842 · see citing works
Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency
Farooqi, I. S., Yeo, G. S. H., Keogh, J. M., Aminian, S., Jebb, S. A., Butler, G. E., Cheetham, T. D., & O’Rahilly, S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9397 · Cited by 801 · see citing works
Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum
Hardy, T., Oakley, F., Anstee, Q. M., & Day, C. P. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044224 · Cited by 619 · see citing works
Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats
Tang-Christensen, M., Larsen, P. J., Goke, R., Fink-Jensen, A., Jessop, D. S., Moller, M., & Sheikh, S. P. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.271.4.r848 · Cited by 597 · see citing works
Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist
Kühnen, P., Clément, K., Wiegand, S., Blankenstein, O., Gottesdiener, K., Martini, L. L., Mai, K., Blume-Peytavi, U., Grüters, A., & Krude, H. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1512693 · Cited by 485 · see citing works
Modulation of Blood Pressure by Central Melanocortinergic Pathways
Greenfield, J. R., Miller, J. W., Keogh, J. M., Henning, E., Satterwhite, J. H., Cameron, G. S., Astruc, B., Mayer, J. P., Brage, S., See, T. C., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0803085 · Cited by 477 · see citing works
Distribution of GLP‐1 Binding Sites in the Rat Brain: Evidence that Exendin‐4 is a Ligand of Brain GLP‐1 Binding Sites
Göke, R., Larsen, P. J., Mikkelsen, J. D., & Sheikh, S. P. (1995) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1995.tb00650.x · Cited by 474 · see citing works
Discovery, characterization, and clinical development of the glucagon-like peptides
Drucker, D. J., Habener, J. F., & Holst, J. J. (2017) · Journal of Clinical Investigation · doi:10.1172/jci97233 · Cited by 418 · see citing works
Self-citation
Binge Eating as a Major Phenotype of Melanocortin 4 Receptor Gene Mutations
Branson, R., Potoczna, N., Kral, J. G., Lentes, K., Hoehe, M. R., & Horber, F. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa021971 · Cited by 367 · see citing works
Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4
Kanoski, S. E., Fortin, S. M., Arnold, M., Grill, H. J., & Hayes, M. R. (2011) · Endocrinology · doi:10.1210/en.2011-0174 · Cited by 347 · see citing works
Arcuate Glucagon-Like Peptide 1 Receptors Regulate Glucose Homeostasis but Not Food Intake
Sandoval, D. A., Bagnol, D., Woods, S. C., D’Alessio, D. A., & Seeley, R. J. (2008) · Diabetes · doi:10.2337/db07-1824 · Cited by 316 · see citing works
Review of head‐to‐head comparisons of glucagon‐like peptide‐1 receptor agonists
Madsbad, S. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12596 · Cited by 305 · see citing works
Self-citation
Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency
Collet, T.-H., Dubern, B., Mokrosinski, J., Connors, H., Keogh, J. M., Mendes de Oliveira, E., Henning, E., Poitou-Bernert, C., Oppert, J.-M., Tounian, P., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.06.015 · Cited by 302 · see citing works
The Central Melanocortin System and the Integration of Short- and Long-term Regulators of Energy Homeostasis
Ellacott, K. L. J. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.395 · Cited by 262 · see citing works
Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms
Yeo, G. S. H. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg057 · Cited by 241 · see citing works
Melanocortin-4 Receptor Gene: Case-Control Study and Transmission Disequilibrium Test Confirm that Functionally Relevant Mutations Are Compatible with a Major Gene Effect for Extreme Obesity
Hinney, A., Hohmann, S., Geller, F., VOGEL, C., Hess, C., Wermter, A., Brokamp, B., Goldschmidt, H., Siegfried, W., Remschmidt, H., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030233 · Cited by 207 · see citing works
Effect of liraglutide on ectopic fat in polycystic ovary syndrome: <scp>A</scp> randomized clinical trial
Frøssing, S., Nylander, M., Chabanova, E., Frystyk, J., Holst, J. J., Kistorp, C., Skouby, S. O., & Faber, J. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13053 · Cited by 178 · see citing works
Self-citation
Prevalence of Mutations and Functional Analyses of Melanocortin 4 Receptor Variants Identified among 750 Men with Juvenile-Onset Obesity
Larsen, L. H., Echwald, S. M., Sørensen, T. I. A., Andersen, T., Wulff, B. S., & Pedersen, O. B. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0497 · Cited by 176 · see citing works
Lifestyle Intervention in Obese Children With Variations in the Melanocortin 4 Receptor Gene
Reinehr, T., Hebebrand, J., Friedel, S., Toschke, A. M., Brumm, H., Biebermann, H., & Hinney, A. (2009) · Obesity · doi:10.1038/oby.2008.422 · Cited by 166 · see citing works
Pharmacological Characterization of 40 Human Melanocortin-4 Receptor Polymorphisms with the Endogenous Proopiomelanocortin-Derived Agonists and the Agouti-Related Protein (AGRP) Antagonist,
Xiang, Z., Litherland, S. A., Sorensen, N. B., Proneth, B., Wood, M. S., Shaw, A. M., Millard, W. J., & Haskell‐Luevano, C. (2006) · Biochemistry · doi:10.1021/bi0600300 · Cited by 146 · see citing works
The Hypothalamic Glucagon-Like Peptide 1 Receptor Is Sufficient but Not Necessary for the Regulation of Energy Balance and Glucose Homeostasis in Mice
Burmeister, M. A., Ayala, J. E., Smouse, H., Landivar-Rocha, A., Brown, J. D., Drucker, D. J., Stoffers, D. A., Sandoval, D. A., Seeley, R. J., & Ayala, J. E. (2017) · Diabetes · doi:10.2337/db16-1102 · Cited by 136 · see citing works
Impact of weight change on quality of life in adults with overweight/obesity in the United States: a systematic review
Kroes, M., Osei-Assibey, G., Baker-Searle, R., & Huang, J. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1128403 · Cited by 121 · see citing works
Genetic variants in LEP, LEPR, and MC4R explain 30% of severe obesity in children from a consanguineous population
Saeed, S., Bonnefond, A., Manzoor, J., Shabir, F., Ayesha, H., Philippe, J., Durand, E., Crouch, H. K., Sand, O., Ali, M. A., et al. (2015) · Obesity · doi:10.1002/oby.21142 · Cited by 115 · see citing works
Poor Cell Surface Expression of Human Melanocortin-4 Receptor Mutations Associated with Obesity
Nijenhuis, W. A. J., Garner, K. M., van Rozen, R. J., & Adan, R. A. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211326200 · Cited by 115 · see citing works
Functional Analyses of Melanocortin-4 Receptor Mutations Identified from Patients with Binge Eating Disorder and Nonobese or Obese Subjects
Tao, Y., & Segaloff, D. L. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0519 · Cited by 102 · see citing works
Melanocortin 4 Receptor Mutations in Obese Czech Children: Studies of Prevalence, Phenotype Development, Weight Reduction Response, and Functional Analysis
Hainerová, I. A., Larsen, L. H., Holst, B., Finková, M., Hainer, V., Lebl, J., Hansen, T. F., & Pedersen, O. B. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0352 · Cited by 88 · see citing works
Self-citation
Impact Sibutramine Therapy in Children with Hypothalamic Obesity or Obesity with Aggravating Syndromes
Danielsson, P., Janson, A., Norgren, S., & Marcus, C. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0826 · Cited by 84 · see citing works
Identification and Characterization of Melanocortin-4 Receptor Gene Mutations in Morbidly Obese Finnish Children and Adults
Valli‐Jaakola, K., Lipsanen‐Nyman, M., Oksanen, L., Hollenberg, A. N., KONTULA, K. K., Bjørbæk, C., & Schalin‐Jäntti, C. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031182 · Cited by 81 · see citing works
Weight Loss after Roux-en-Y Gastric Bypass in Obese Patients Heterozygous for MC4R Mutations
Aslan, I. R., Campos, G. M., Calton, M. A., Evans, D. S., Merriman, R. B., & Vaisse, C. (2010) · Obesity Surgery · doi:10.1007/s11695-010-0295-8 · Cited by 78 · see citing works
Greater Impact of Melanocortin-4 Receptor Deficiency on Rates of Growth and Risk of Type 2 Diabetes During Childhood Compared With Adulthood in Pima Indians
Thearle, M. S., Muller, Y. L., Hanson, R. L., Mullins, M., Abdussamad, M., Tran, J., Knowler, W. C., Bogardus, C., Krakoff, J. A., & Baier, L. J. (2011) · Diabetes · doi:10.2337/db11-0708 · Cited by 62 · see citing works
Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort
Vollbach, H., Brandt, S., Lahr, G., Denzer, C., von Schnurbein, J., Debatin, K., & Wabitsch, M. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.161 · Cited by 62 · see citing works
Evaluation of a target region capture sequencing platform using monogenic diabetes as a study-model
Gao, R., Liu, Y., Gjesing, A. P., Hollensted, M., Wan, X., He, S., Pedersen, O. B., Yi, X., Wang, J., & Hansen, T. F. (2014) · BMC Genetics · doi:10.1186/1471-2156-15-13 · Cited by 59 · see citing works
Self-citation
Pharmacological Characterization of 30 Human Melanocortin-4 Receptor Polymorphisms with the Endogenous Proopiomelanocortin-Derived Agonists, Synthetic Agonists, and the Endogenous Agouti-Related Protein Antagonist,
Xiang, Z., Proneth, B., Dirain, M. L. S., Litherland, S. A., & Haskell‐Luevano, C. (2010) · Biochemistry · doi:10.1021/bi100068u · Cited by 54 · see citing works
Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study
Bonnefond, A., Keller, R., Meyre, D., Stutzmann, F., Thuillier, D., Stefanov, D. G., Froguel, P., Horber, F., & Kral, J. G. (2016) · Diabetes Care · doi:10.2337/dc16-0115 · Cited by 53 · see citing works
Peptide and Small Molecules Rescue the Functional Activity and Agonist Potency of Dysfunctional Human Melanocortin-4 Receptor Polymorphisms,
Xiang, Z., Pogozheva, I. D., Sorenson, N. B., Wilczynski, A. M., Holder, J. R., Litherland, S. A., Millard, W. J., Mosberg, H. I., & Haskell‐Luevano, C. (2007) · Biochemistry · doi:10.1021/bi7007382 · Cited by 40 · see citing works
Role of the brain melanocortins in blood pressure regulation
do Carmo, J. M., da Silva, A. A., Wang, Z., Fang, T., Aberdein, N., Perez de Lara, C. E., & Hall, J. E. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.03.003 · Cited by 38 · see citing works
Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase response
Malik, I. A., Triebel, J., Posselt, J., Khan, S., Ramadori, P., Raddatz, D., & Ramadori, G. P. (2011) · Histochemistry and Cell Biology · doi:10.1007/s00418-011-0899-7 · Cited by 27 · see citing works
The contribution of serotonin 5-HT2C and melanocortin-4 receptors to the satiety signaling of glucagon-like peptide 1 and liragultide, a glucagon-like peptide 1 receptor agonist, in mice
Nonogaki, K., Suzuki, M., Sanuki, M., Wakameda, M., & Tamari, T. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.06.175 · Cited by 20 · see citing works
1H MRS assessment of hepatic steatosis in overweight children and adolescents: comparison between 3T and open 1T MR-systems
Chabanova, E., Bille, D. S., Thisted, E., Holm, J., & Thomsen, H. S. (2012) · Abdominal Imaging · doi:10.1007/s00261-012-9930-2 · Cited by 19 · see citing works
Self-citation
Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
Lede, V., Meusel, A., Garten, A., Popkova, Y., Penke, M., Franke, C., Ricken, A. M., Schulz, A., Kieß, W., Huster, D., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172000 · Cited by 18 · see citing works
Chronic intrahypothalamic rather than subcutaneous liraglutide treatment reduces body weight gain and stimulates the melanocortin receptor system
Kaineder, K., Birngruber, T., Rauter, G., Obermüller, B., Eichler, J., Münzker, J., Al-Zoughbi, W., Mautner, S., Torekov, S. S., Hartmann, B., et al. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.98 · Cited by 11 · see citing works
Self-citation

Flagged first, then by citations

2 of the 59 references couldn’t be matched to a known paper.

Sorted by citations

Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined
Lundgren, J. R., Janus, C., Jensen, S. B. K., Juhl, C. R., Olsen, L. M., Christensen, R. M., Svane, M. S., Bandholm, T., Bojsen-Møller, K. N., Blond, M. B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2028198 · Cited by 536 · see citing works
Self-citation
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
Melanocortin-4 Receptor Signalling: Importance for Weight Regulation and Obesity Treatment
Kühnen, P., Krude, H., & Biebermann, H. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.12.002 · Cited by 190 · see citing works
New insights into the treatment of obesity
Blüher, M., Aras, M., Aronne, L. J., Batterham, R. L., Giorgino, F., Ji, L., Pietiläinen, K. H., Schnell, O., Tonchevska, E., & Wilding, J. P. H. (2023) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15077 · Cited by 158 · see citing works
“ment with liraglutide has been shown to benefit patients with obesity caused by MC4R mutations.(64,65) However, liraglutide has not been approved for this indication.”
Background
The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits
Hinney, A., Körner, A., & Fischer-Posovszky, P. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00716-0 · Cited by 101 · see citing works
GLP‐1 agonists for obesity and type 2 diabetes in children: Systematic review and meta‐analysis
Chadda, K. R., Cheng, T. S., & Ong, K. K. (2020) · Obesity Reviews · doi:10.1111/obr.13177 · Cited by 103 · see citing works
Levels of circulating semaglutide determine reductions in HbA1c and body weight in people with type 2 diabetes
Overgaard, R. V., HERTZ, C. L., Ingwersen, S. H., Navarria, A., & Drucker, D. J. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100387 · Cited by 102 · see citing works
The regulation of PKA signaling in obesity and in the maintenance of metabolic health
London, E., & Stratakis, C. A. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108113 · Cited by 95 · see citing works
The role of polygenic susceptibility to obesity among carriers of pathogenic mutations in MC4R in the UK Biobank population
Chami, N., Preuss, M. H., Walker, R. W., Moscati, A., & Loos, R. J. F. (2020) · PLoS Medicine · doi:10.1371/journal.pmed.1003196 · Cited by 84 · see citing works
“Besides genetic factors, nongenetic factors may also partially explain why some carriers are able to remain of normal weight, as weight loss surgery [46–48], lifestyle interventions [49,50], and weight loss medication [51] have been shown to affect the weight of MC4R mutation carriers to some extent.”
Background
Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation
Brouwers, B., de Oliveira, E. M., Martí-Solano, M., Filippin-Monteiro, F. B., Laurin, S., Keogh, J. M., Henning, E., Bounds, R., Daly, C. A., Houston, S., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108862 · Cited by 79 · see citing works
“People with heterozygous MC4R deficiency can respond to treatment with the GLP-1 receptor agonist liraglutide (Iepsen et al., 2018) and with Roux-en-Y-bypass surgery (Hatoum et al.”
Background
What Is an L-Cell and How Do We Study the Secretory Mechanisms of the L-Cell?
Kuhre, R. E., Deacon, C. F., Holst, J. J., & Petersen, N. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.694284 · Cited by 79 · see citing works
“on L-cell secretion, and have, for instance been used to elucidate molecular mechanisms involved in the appetite and weight reducing effects of GLP-1 based treatment in a certain patient population (158).”
MethodSelf-citation
Current Treatments for Patients with Genetic Obesity
Faccioli, N., Poitou, C., Clément, K., & Dubern, B. (2023) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2023.2023-3-2 · Cited by 86 · see citing works
“An equivalent weight loss between the two groups of about 6% of body weight after 16 weeks of treatment was observed with similar improvement in body fat mass, waist circumference, and glucose tolerance (52).”
Background
The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis
Wu, Y., He, H., Cheng, Z., Bai, Y., & Ma, X. (2019) · Current Protein and Peptide Science · doi:10.2174/1389203720666190125105401 · Cited by 76 · see citing works
Intestine-selective reduction of Gcg expression reveals the importance of the distal gut for GLP-1 secretion
Panaro, B. L., Yusta, B., Matthews, D., Koehler, J. A., Song, Y., Sandoval, D. A., & Drucker, D. J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.100990 · Cited by 67 · see citing works
Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center
Kleinendorst, L., Abawi, O., van der Voorn, B., Jongejan, M. H. T. M., Brandsma, A. E., Visser, J. A., van Rossum, E. F. C., van der Zwaag, B., Alders, M., Boon, E. M. J., et al. (2020) · PLOS ONE · doi:10.1371/journal.pone.0232990 · Cited by 62 · see citing works
“[52] Recently, it was suggested that a subgroup of patients with severe early-onset obesity might have relative leptin deficiency and therefore might benefit from recombinant leptin administration.”
Background
Hypothalamic obesity: from basic mechanisms to clinical perspectives
Argente, J., Farooqi, I. S., Chowen, J. A., Kühnen, P., López, M., Morselli, E., Gan, H.-W., Spoudeas, H. A., Wabitsch, M., & Tena-Sempere, M. (2025) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00283-3 · Cited by 57 · see citing works
Childhood Obesity: Position Statement of Polish Society of Pediatrics, Polish Society for Pediatric Obesity, Polish Society of Pediatric Endocrinology and Diabetes, the College of Family Physicians in Poland and Polish Association for Study on Obesity
Mazur, A., Zachurzok, A., Baran, J., Dereń, K., Łuszczki, E., Weres, A., Wyszyńska, J., Dylczyk, J., Szczudlik, E., Drożdż, D., et al. (2022) · Nutrients · doi:10.3390/nu14183806 · Cited by 62 · see citing works
“with MC4R mutations, and obesity related to Kinase suppressor of Ras 2 mutation is well treated with metformin [51,52].”
Background
Obesity: exploring its connection to brain function through genetic and genomic perspectives
Saeed, S., Bonnefond, A., & Froguel, P. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02737-9 · Cited by 53 · see citing works
Rare genetic forms of obesity: From gene to therapy
Clément, K., Mosbah, H., & Poitou, C. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113134 · Cited by 53 · see citing works
Aberrant expression of agouti signaling protein (ASIP) as a cause of monogenic severe childhood obesity
Kempf, E., Landgraf, K., Stein, R., Hanschkow, M., Hilbert, A., Jamra, R. A., Boczki, P., Herberth, G., Kühnapfel, A., Tseng, Y., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00703-9 · Cited by 47 · see citing works
“…treatment option might be glucagon-like peptide-1 receptor (GLP-1R) agonists as they have been shown to mediate weight loss in patients with MC4R mutations to a similar degree as in patients with polygenic obesity 39 ; however, they would not target the underlying pathomechanisms at the MC4R.”
The Regulatory Role of the Central and Peripheral Serotonin Network on Feeding Signals in Metabolic Diseases
Nonogaki, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031600 · Cited by 46 · see citing works
“Moreover, in obese humans with MC4R mutations, liraglutide causes weight loss [55,56].”
Background
Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity
Pressley, H., Cornelio, C. K., & Adams, E. N. (2022) · Journal of Pharmacy Technology · doi:10.1177/87551225221116010 · Cited by 46 · see citing works
GLP-1 Receptor Agonist Treatment in Morbid Obesity and Type 2 Diabetes Due to Pathogenic Homozygous Melanocortin-4 Receptor Mutation: A Case Report
Iepsen, E. W., Have, C. T., Veedfald, S., Madsbad, S., Holst, J. J., Grarup, N., Pedersen, O., Brandslund, I., Holm, J.-C., Hansen, T., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100006 · Cited by 43 · see citing works
“Accordingly, with our previous article on heterozygous carriers with pathogenic MC4R mutation,5 together with this case report, there is good support for a conclusion that GLP-1 RAs act independently of the MC4R in individuals with severe obesity due to both heterozygous and homozygous pathogenic mutations in the MC4R.”
BackgroundResultInfluentialSelf-citation
MECHANISMS IN ENDOCRINOLOGY: Update on treatments for patients with genetic obesity
Poitou, C., Mosbah, H., & Clément, K. (2020) · European Journal of Endocrinology · doi:10.1530/eje-20-0363 · Cited by 43 · see citing works
Exploratory analysis of eating-and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment
Jensen, S. B. K., Janus, C., Lundgren, J. R., Juhl, C. R., Sandsdal, R. M., Olsen, L. M., Andresen, A., Borg, S. A., Jacobsen, I. C., Finlayson, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32307-y · Cited by 42 · see citing works
Self-citation
Melanocortin‐4 receptor complexity in energy homeostasis,obesity and drug development strategies
Fatima, M. T., Ahmed, I., Fakhro, K. A., & Akil, A. A. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14618 · Cited by 41 · see citing works
“It has been reported to be effective in many cases of monogenic obesity.(109)”
Background
Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management
d’Aquino, A. I., Maikawa, C. L., Nguyen, L. T., Lu, K., Hall, I. A., Jons, C. K., Kasse, C. M., Yan, J., Prossnitz, A. N., Chang, E., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101292 · Cited by 49 · see citing works
Hypothalamic neuropeptides and neurocircuitries in Prader Willi syndrome
Corrêa-da-Silva, F., Fliers, E., Swaab, D., & Yi, C. (2021) · Journal of neuroendocrinology · doi:10.1111/jne.12994 · Cited by 34 · see citing works
Hypothalamic MC4R regulates glucose homeostasis through adrenaline-mediated control of glucose reabsorption via renal GLUT2 in mice
Cordeiro, L. M. D. S., Elsheikh, A., Devisetty, N., Morgan, D. A., Ebert, S. N., Rahmouni, K., & Chhabra, K. H. (2020) · Diabetologia · doi:10.1007/s00125-020-05289-z · Cited by 40 · see citing works
Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations
Trier, C., Hollensted, M., Schnurr, T. M., Lund, M. A. V., Nielsen, T. R. H., Rui, G., Andersson, E. A., Svendstrup, M., Bille, D. S., Gjesing, A. P., et al. (2021) · International Journal of Obesity · doi:10.1038/s41366-020-00673-6 · Cited by 38 · see citing works
Self-citation
Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists
Sandsdal, R. M., Juhl, C. R., & Torekov, S. S. (2019) · Drug Safety · doi:10.1007/s40264-019-00812-7 · Cited by 36 · see citing works
Self-citation
High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor
Saeed, S., Khanam, R., Janjua, Q. M., Manzoor, J., Ning, L., Hanook, S., Canouil, M., Ali, M. A., Ayesha, H., Khan, W. I., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101187 · Cited by 36 · see citing works
Obesity medication lorcaserin activates brainstem GLP-1 neurons to reduce food intake and augments GLP-1 receptor agonist induced appetite suppression
Wagner, S., Brierley, D. I., Leeson-Payne, A., Jiang, W., Chianese, R., Lam, B. Y. H., Dowsett, G. K. C., Cristiano, C., Lyons, D., Reimann, F., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101665 · Cited by 32 · see citing works
“In contrast to lorcaserin, GLP-1R agonists liraglutide and exendin-4 did not require functional MC4Rs to impact feeding in mice (Figure 4B-C), which corroborates an earlier report in humans with MC4R mutations who were prescribed liraglutide [46].”
How do glucagon‐like Peptide‐1 receptor agonists affect measures of muscle mass in individuals with, and without, type 2 diabetes: A systematic review and meta‐analysis
Anyiam, O., Ardavani, A., Rashid, R. S. A., Panesar, A., & IDRIS, I. R. (2025) · Obesity Reviews · doi:10.1111/obr.13916 · Cited by 39 · see citing works
Impact of Genetic Variations and Epigenetic Mechanisms on the Risk of Obesity
Chiurazzi, M., Cozzolino, M., Orsini, R. C., Maro, M. D., Minno, M. N. D. D., & Colantuoni, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239035 · Cited by 32 · see citing works
Beyond Glucagon-like Peptide-1: Is G-Protein Coupled Receptor Polypharmacology the Path Forward to Treating Metabolic Diseases?
Sloop, K. W., Briere, D. A., Emmerson, P. J., & Willard, F. S. (2018) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.8b00009 · Cited by 31 · see citing works
Short-term GLP-1 receptor agonist exenatide ameliorates intramyocellular lipid deposition without weight loss in ob/ob mice
Xu, F., Cao, H., Chen, Z., Gu, H., Guo, W., Lin, B., & Weng, J. (2020) · International Journal of Obesity · doi:10.1038/s41366-019-0513-y · Cited by 31 · see citing works
Monogenic Obesity; Using Drugs to Bypass the Problem
Coll, A. P. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.015 · Cited by 28 · see citing works
AMPK in the Ventromedial Nucleus of the Hypothalamus: A Key Regulator for Thermogenesis
Liu, H., Xu, Y., & Hu, F. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.578830 · Cited by 28 · see citing works
“The weight reducing effects of liraglutide on human subjects have been confirmed by many clinical studies, although whether the decrease in body weight is linked to increased energy expenditure or not remains elusive (91, 92).”
Background
Differentiating monogenic and syndromic obesities from polygenic obesity: Assessment, diagnosis, and management
Fitch, A., Malhotra, S., & Conroy, R. (2024) · Obesity Pillars · doi:10.1016/j.obpill.2024.100110 · Cited by 27 · see citing works
“Larger-scale randomized controlled trials are needed to determine if GLP-1R agonists are efficacious for weight and hunger improvement in this population [104].”
BackgroundResult
Effects of glucagon‐like peptide‐1 analogue treatment in genetic obesity: A case series
Welling, M. S., de Groot, C. J., Kleinendorst, L., van der Voorn, B., Burgerhart, J. S., van der Valk, E. S., van Haelst, M. M., van den Akker, E. L. T., & van Rossum, E. F. C. (2021) · Clinical Obesity · doi:10.1111/cob.12481 · Cited by 24 · see citing works
“on the effects of liraglutide treatment in patients with heterozygous pathogenic MC4R variants and, even more importantly, in a patient with a homozygous pathogenic MC4R variant.(13,14) Moreover, in mice neither the mc4r nor the serotonin 5-ht2c receptor seemed to be required for the anorexigenic effect of liraglutide.”
BackgroundResult
Pharmacotherapy in Childhood Obesity
Kühnen, P., Biebermann, H., & Wiegand, S. (2021) · Hormone Research in Paediatrics · doi:10.1159/000518432 · Cited by 25 · see citing works
Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar
Mohammed, I., Haris, B., Al-Barazenji, T., Vasudeva, D., Tomei, S., Al-Azwani, I. K., Dauleh, H., Shehzad, S., Chirayath, S., Mohamadsalih, G., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad366 · Cited by 25 · see citing works
Genetic Obesity Disorders: Body Mass Index Trajectories and Age of Onset of Obesity Compared with Children with Obesity from the General Population
Abawi, O., Wahab, R. J., Kleinendorst, L., Blankers, L., Brandsma, A. E., van Rossum, E. F. C., van der Voorn, B., van Haelst, M. M., Gaillard, R., & van den Akker, E. L. T. (2023) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2023.113619 · Cited by 25 · see citing works
Association and interaction of the MC4R rs17782313 polymorphism with plasma ghrelin, GLP-1, cortisol, food intake and eating behaviors in overweight/obese Iranian adults
Rahati, S., Qorbani, M., Naghavi, A., & Pishva, H. (2022) · BMC Endocrine Disorders · doi:10.1186/s12902-022-01129-w · Cited by 24 · see citing works
Pharmacogenetic Interactions of Medications Administered for Weight Loss in Adults: A Systematic Review and Meta-Analysis
BouSaba, J., Vosoughi, K., Dilmaghani, S., Prokop, L. J., & Camilleri, M. (2023) · Pharmacogenomics · doi:10.2217/pgs-2022-0192 · Cited by 22 · see citing works
Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency
Fojas, E. G., Radha, S. K., Ali, T., Nadler, E. P., & Lessan, N. G. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.792354 · Cited by 21 · see citing works
“Liraglutide treatment for 16 weeks has been reported to result in comparable weight loss and decrease in HbA1c in patients with MC4R-d and controls (35, 36).”
Background
Pharmacological profile of once-weekly injectable semaglutide for chronic weight management
Lau, D. C. W., Batterham, R. L., & le Roux, C. W. (2022) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2022.2070473 · Cited by 22 · see citing works
“In addition to being indicated as a treatment for T2D and chronic weight management (including patients with obesity with a monogenetic etiology) [74], subcutaneous semaglutide is currently being investigated as a treatment option for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH).”
Background
GPR120 Regulates Pancreatic Polypeptide Secretion From Male Mouse Islets via PLC-Mediated Calcium Mobilization
Zhao, Y.-F., Li, X., Liang, X., Zhao, Y., Xie, R., Zhang, L., Zhang, X., & Chen, C. (2020) · Endocrinology · doi:10.1210/endocr/bqaa157 · Cited by 20 · see citing works
Resting Energy Expenditure and Body Composition in Children and Adolescents With Genetic, Hypothalamic, Medication-Induced or Multifactorial Severe Obesity
Abawi, O., Koster, E. C., Welling, M. S., Boeters, S. C. M., van Rossum, E. F. C., van Haelst, M. M., van der Voorn, B., de Groot, C. J., & van den Akker, E. L. T. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.862817 · Cited by 19 · see citing works
MC4R in Central and Peripheral Systems
Wei, R., Li, D., Jia, S., Chen, Y., & Wang, J. (2023) · Advanced Biology · doi:10.1002/adbi.202300035 · Cited by 18 · see citing works
Medical semiology of patients with monogenic obesity: A systematic review
Renard, É., Thevenard-Berger, A., & Meyre, D. (2024) · Obesity Reviews · doi:10.1111/obr.13797 · Cited by 18 · see citing works
“198,199 3”
Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency
Bhatnagar, P., Ahmad, N. N., Li, X., Coghlan, M., Kaplan, L. M., & Farooqi, I. S. (2025) · Nature Medicine · doi:10.1038/s41591-025-03913-2 · Cited by 20 · see citing works
“GLP-1 receptor agonists predominantly target non-MC4R-dependent neural pathways in mice 19 , and there is evidence from a small clinical study with liraglutide 20 that they may be effective in people with MC4R deficiency.”
A Gut-Intrinsic Melanocortin Signaling Complex Augments L-Cell Secretion in Humans
Sun, E. W. L., Iepsen, E. W., Pezos, N., Lumsden, A. L., Martin, A. M., Schober, G., Isaacs, N. J., Rayner, C. K., Nguyen, N. Q., de Fontgalland, D., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.04.014 · Cited by 17 · see citing works
Self-citation
The melanocortin‐4 receptor pathway and the emergence of precision medicine in obesity management
Fansa, S., & Acosta, A. J. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15555 · Cited by 17 · see citing works
The Impact of ACEs on BMI: An Investigation of the Genotype-Environment Effects of BMI
Schlauch, K., Read, R., Neveux, I., Lipp, B., Slonim, A., & Grzymski, J. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.816660 · Cited by 12 · see citing works
“Genetic links with obesity have also been well established, and most genetic associations include a “standard” set of obesityrelated genes and common variants (Frayling et al., 2007; Scuteri et al., 2007; Loos et al., 2008; Song et al., 2008; Willer et al., 2009; Speliotes et al., 2010; Graff et al., 2013; Namjou et a…”
Background
Genetic variation in satiety signaling and hypothalamic inflammation: merging fields for the study of obesity
Szalanczy, A., Chuang, C., & Woods, L. C. S. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108928 · Cited by 17 · see citing works
Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass
Iepsen, E. W., Zhang, J., Hollensted, M., Madsbad, S., Hansen, T., Holst, J. J., Jørgensen, N. R., Holm, J.-C., & Torekov, S. S. (2020) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-019-01034-8 · Cited by 15 · see citing works
Self-citation
G lucagon‐like peptide‐1 analogues in monogenic syndromic obesity: Real‐world data from a large cohort of Alström syndrome patients
Ali, S., Baig, S., Wanninayake, S., Xavier, G. D. S., Dawson, C., Paisey, R., & Geberhiwot, T. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15398 · Cited by 15 · see citing works
The cost-effectiveness analysis of semaglutide for the treatment of adult and adolescent patients with overweight and obesity: a systematic review
Asiabar, A. S., Rezaei, M. A., Jafarzadeh, D., Rajaei, S., Atefimanesh, P., Soleimanpour, S., Meher, M. H. K., & Azari, S. (2024) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-024-03755-w · Cited by 15 · see citing works
Mutations in melanocortin-4 receptor: From fish to men
Tao, Y. (2022) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2022.03.003 · Cited by 14 · see citing works
Syndromic and Monogenic Obesity: New Opportunities Due to Genetic-Based Pharmacological Treatment
Kalinderi, K., Goula, V., Sapountzi, E., Tsinopoulou, V. R., & Fidani, L. (2024) · Children · doi:10.3390/children11020153 · Cited by 13 · see citing works
“…for 16 weeks in a woman with homozygous pathogenic MC4R mutation, morbid obesity, and T2D, resulting in a decrease in body weight of ~10 kg, similar to weight loss in heterozygous MC4R mutation carriers and common obesity; thus, it can act independently of the MC4R mutation status [76,77].”
Background
Comparison of weight loss and adverse events of obesity drugs in children and adolescents: a systematic review and meta-analysis
Zhao, G., Zhang, Q., Wu, F., Yin, S., Xie, Y., & Liu, H. (2022) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2022.2117152 · Cited by 13 · see citing works
“Although the patients in this study were mainly adults and young people, it could provide ideas for the future treatment of childhood obesity in melanocortin-4 receptor mutations [45].”
Background
A narrative review of current trends in liraglutide: insights into the unmet needs in management of type 2 diabetes and obesity
Hasanzad, M., Sarhangi, N., Nikfar, S., Ostad, S. N., & Meybodi, H. R. A. (2020) · Journal of Diabetes & Metabolic Disorders · doi:10.1007/s40200-020-00619-9 · Cited by 13 · see citing works
Semaglutide, a Long-Acting GLP-1 Analogue, for the Management of Early-Onset Obesity due to MC4R Defect: A Case Report
Gokul, P. R., Apperley, L. J., Parkinson, J., Clark, K., Lund, K., Owens, M., & Senniappan, S. (2024) · Hormone Research in Paediatrics · doi:10.1159/000537921 · Cited by 10 · see citing works
“Liraglutide, a glucagon-like peptide (GLP-1) analogue, has been shown to be bene ﬁ cial in some individuals with pathogenic MC4R mutation [5].”
Pharmacogenomics of Tirzepatide: Genomic Insights into Dual GIP/GLP-1 Agonist Response in Type 2 Diabetes and Atherosclerosis
Song, Z., Tang, Y., Peng, M., Han, R., & He, P. (2025) · Pharmaceuticals · doi:10.3390/ph18091261 · Cited by 11 · see citing works
“Variants in key obesity-related genes, such as FTO and MC4R, may influence individual variability in this response [51–53].”
Proopiomelanocortin deficiency diagnosed in infancy in two boys and a review of the known cases
Graves, L. E., Khouri, J. M., Kristidis, P., & Verge, C. F. (2021) · Journal of Paediatrics and Child Health · doi:10.1111/jpc.15407 · Cited by 11 · see citing works
Rare genetic forms of obesity in childhood and adolescence: A narrative review of the main treatment options with a focus on innovative pharmacological therapies
Mainieri, F., Bella, S. L., Rinaldi, M., & Chiarelli, F. (2024) · European Journal of Pediatrics · doi:10.1007/s00431-024-05427-4 · Cited by 11 · see citing works
“Treatment with liraglutide, a GLP1 analogue, has led to weight loss in terms of adipose and lean mass, as well as improvement in metabolic parameters, in patients carrying pathogenic variants of MC4R due to the pro-satiating effect of GLP1 analogues [55–57].”
Case report: Nerve fiber regeneration in children with melanocortin 4 receptor gene mutation related obesity treated with semaglutide
Gad, H., Mohammed, I., Dauleh, H., Pasha, M., Al-Barazenji, T., Hussain, K., & Malik, R. A. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1385463 · Cited by 10 · see citing works
Glucagon-Like Peptide 1 (GLP-1) Action on Hypothalamic Feeding Circuits
Hwang, E., Portillo, B., & Williams, K. W. (2025) · Endocrinology · doi:10.1210/endocr/bqaf125 · Cited by 10 · see citing works
Novel therapeutics in rare genetic obesities: A narrative review
Dubern, B., Faccioli, N., Poitou, C., & Clément, K. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106763 · Cited by 11 · see citing works
Updates on Rare Genetic Variants, Genetic Testing, and Gene Therapy in Individuals With Obesity
Zuccaro, M. V., LeDuc, C. A., & Thaker, V. (2024) · Current Obesity Reports · doi:10.1007/s13679-024-00567-y · Cited by 10 · see citing works
“Some reports have suggested that glucagon-like peptide 1 (GLP1) analogs might be effective in the treatment of individuals with MC4R deficiency [103], Alström syndrome [104 •• ], 16p11.”
Pharmacological treatment strategies for patients with monogenic obesity
Kühnen, P., Wiegand, S., & Biebermann, H. (2020) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2020-0129 · Cited by 10 · see citing works
“Recently, the successful treatment of patients with heterozygous MC4R mutations with the GLP1R agonist Liraglutide has been described [26].”
Background
Liraglutide Treatment in a Morbidly Obese Adolescent with a MC4R Gene Variant: Side Effects Reduce Success
Çamtosun, E., Akıncı, A., Kayaş, L., Çiftçi, N., & Tekedereli, İ. (2021) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2021.2021.0158 · Cited by 10 · see citing works
“89 SDS), and upon obtaining the consent of the family, liraglutide treatment was initiated (8).”
BackgroundInfluential
Clinical, genetic, and epidemiological survey of Polish children and adolescents with severe obesity: A study protocol of the Polish–German study project on severe early-onset obesity
Mierzwa, M., Bik-Multanowski, M., Ranke, M. B., Brandt, S., Flehmig, B., Małecka‐Tendera, E., Mazur, A., Petriczko, E., Wabitsch, M., Wójcik, M., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.972174 · Cited by 9 · see citing works
“, glucagon-like peptide 1 (GLP-1) agonist is effective in weight reduction in patients with MC4R mutations, and obesity related to Kinase Suppressor of Ras-2 (KSR2) mutation is well treated with metformin (21, 28, 30).”
Background
Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions
Salazar-Valencia, I. G., Villamil‐Ramírez, H., Barajas-Olmos, F. M., Guevara‐Cruz, M., Kauffer, L. R. M., Garcia‐Ortíz, H., Hernández-Vergara, O., de Sandy-Galán, D. A. D., León‐Mimila, P., Centeno-Cruz, F., et al. (2022) · Genes · doi:10.3390/genes13122267 · Cited by 9 · see citing works
“Moreover, the GLP-1 receptor agonist liraglutide was found to induce similar weight loss in obese patients with and without MC4R mutations, suggesting MC4R mutation carriers can be treated with this agonist [17].”
Background
Successful naltrexone-bupropion treatment after several treatment failures in a patient with severe monogenic obesity
Welling, M. S., Mohseni, M., van der Valk, E. S., van Hagen, J. M., Burgerhart, J. S., van Haelst, M. M., & van Rossum, E. F. C. (2023) · iScience · doi:10.1016/j.isci.2023.106199 · Cited by 9 · see citing works
“Earlier studies have shown that liraglutide can induce weight loss and improve hyperphagia in patients with various genetic obesity disorders, such asMC4R deficiency.(11,12) However, to our knowledge, there is no literature available about the effect of NB treatment in patients with genetic obesity disorders.”
BackgroundResultInfluential
Clinical management of patients with genetic obesity during COVID-19 pandemic: position paper of the ESE Growth & Genetic Obesity COVID-19 Study Group and Rare Endo-ERN main thematic group on Growth and Obesity
Groot, C. J. D., Poitou, C., Coupaye, M., Clément, K., Paschou, S. Α., Charmandari, E., Kanaka‐Gantenbein, C., Wabitsch, M., Buddingh, E. P., Nieuwenhuijsen, B., et al. (2021) · Endocrine · doi:10.1007/s12020-021-02619-y · Cited by 9 · see citing works
Reduced Efficacy of Glucagon-Like Peptide-1 Receptor Agonists Therapy in People With Type 1 Diabetes and Genetic Forms of Obesity
Klein, M. P., Aktürk, H. K., Snell‐Bergeon, J. K., & Shah, V. N. (2024) · Journal of Diabetes Science and Technology · doi:10.1177/19322968241245680 · Cited by 9 · see citing works
“16 Their results demonstrated statistically similar responses to Liraglutide treatment (assessed through weight loss and glucose lowering) between those with MC4-R mutations and those without.”
Treatment with liraglutide or naltrexone-bupropion in patients with genetic obesity: a real-world study
Welling, M. S., de Groot, C. J., Mohseni, M., Meeusen, R. E. H., Boon, M. R., van Haelst, M. M., van den Akker, E. L. T., & van Rossum, E. F. C. (2024) · EClinicalMedicine · doi:10.1016/j.eclinm.2024.102709 · Cited by 8 · see citing works
“16 – 18 Given the need for data on pharmacological treat-ment in larger cohorts of patients with genetic obesity, we performed a real-world, observational study in which we will describe the results of treatment with liraglutide or naltrexone-bupropion.”
BackgroundMethod
Sustained Delivery of GLP-1 Receptor Agonists from Injectable Biomimetic Hydrogels Improves Treatment of DiabetesPreprint
d’Aquino, A. I., Maikawa, C. L., Nguyen, L. T., Lu, K., Hall, I. A., Jons, C. K., Kasse, C. M., Yan, J., Prossnitz, A. N., Chang, E., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.28.526057 · Cited by 8 · see citing works
“While this research has the potential to impact people with T2D, as they would benefit directly from a long-acting GLP-1 drug product that can reduce treatment burden and improve disease management, numerous recent studies suggest that such a product can improve the quality of treatment for people with obesity or T1D…”
Background
Exploring the therapeutic potential of precision medicine in rare genetic obesity disorders: a scientific perspective
Collet, T., & Schwitzgebel, V. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1509994 · Cited by 7 · see citing works
Antiobesity Pharmacotherapy for Patients With Genetic Obesity Due to Defects in the Leptin-Melanocortin Pathway
Welling, M. S., van Rossum, E. F. C., & van den Akker, E. L. T. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf004 · Cited by 6 · see citing works
Genetic Landscape of Obesity in Children: Research Advances and Prospects
Khusainova, R. I., Minniakhmetov, I. R., Vasyukova, O. V., Yalaev, B. I., Ринатович, С. Р., Kopytina, D. A., Guseinova, R. M., Dobreva, E. A., Mel'nichenko, G. A., Dedov, I. I., et al. (2025) · Journal of Obesity · doi:10.1155/jobe/9186826 · Cited by 8 · see citing works
“Currently, no available data exist on the use of GLP-1 analogs in other monogenic forms of obesity [159].”
Monogenic obesity due to MC4R deficiency: lessons from a multigenerational case
Giannopoulou, E. Z., Zorn, S., Schirmer, M., Brandt-Heunemann, S., von Schnurbein, J., Nestoris, C., Moawia, A., Siebert, R., Denzer, C., & Wabitsch, M. (2026) · Molecular and Cellular Pediatrics · doi:10.1186/s40348-025-00214-z · Cited by 6 · see citing works
“GLP-1 receptor agonists like liraglutide and semaglu-tide have demonstrated potential for weight loss in this population, though existing studies are limited by small sample sizes [38, 39].”
The Narrative of a Patient with Leptin Receptor Deficiency: Personalized Medicine for a Rare Genetic Obesity Disorder
Welling, M. S., Kleinendorst, L., van Haelst, M. M., & van den Akker, E. L. T. (2023) · Obesity Facts · doi:10.1159/000531529 · Cited by 6 · see citing works
Genetics, pharmacotherapy, and dietary interventions in childhood obesity
Son, J. E. (2024) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2024.12861 · Cited by 9 · see citing works
Tratamiento farmacológico de la obesidad para médicos de Atención Primaria
Rubio, M. Á., Fernández-García, J. M., Andújar, R. C., Altozano, C. S., & Carpi, J. J. U. (2019) · Medicina de Familia SEMERGEN · doi:10.1016/j.semerg.2019.04.005 · Cited by 6 · see citing works
Recommendations for the prevention and management of obesity in the Iraqi population
Nwayyir, H. A., Mutasher, E. M., Alabid, O. M., Jabbar, M. A., Al-Kawaz, W. H. A., Alidrisi, H. A., Alabbood, M., Chabek, M., Alzubaidi, M. A., Alkhazrajy, L. A., et al. (2023) · Postgraduate Medicine · doi:10.1080/00325481.2023.2172914 · Cited by 6 · see citing works
“Pathogenic MC4R mutations are worth considering seeing as patients carrying these mutations can still benefit from Glucagon-like Peptide-1 Receptor Agonists [38,39].”
Background
Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery
Gong, Y., Wu, Q., Huang, S., Fu, Z., Ye, J., Liu, R., Lin, S., Guan, W., Yang, N., Li, J. Z., et al. (2023) · Advanced Biology · doi:10.1002/adbi.202300007 · Cited by 5 · see citing works
From genes to care: the expanding therapeutic horizon in rare genetic obesities
Chalopin, S., Guillon, E., Faucher, P., Dubern, B., Clément, K., & Poitou, C. (2025) · Obesity and Endocrinology · doi:10.1093/obendo/wjaf007 · Cited by 4 · see citing works
The genetics of obesity: aetiology, prevention and therapy
Bonnefond, A., Bruner, W. S., Grant, S. F. A., Morandi, A., & Froguel, P. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01497-w · Cited by 5 · see citing works
“…reports and small series have documented favourable outcomes with agents such as liraglutide (that is, a GLP1 receptor agonist) or bupropion– naltrexone (that is, a dopamine–norepinephrine reuptake inhibitor combined with an opioid receptor antagonist targeting central appetite pathways) 120,121 .”
The Role of GLP1 Receptor Agonists and Multi-agonist Incretin Therapies for Specific Obesity-related Health Conditions: Evidence and Rationale for Prioritisation
Albor, C., Anyiam, O., Boyle, L., Makaronidis, J., Tan, R. J. L., Iftikhar, S., Burzić, A., Lajeunesse‐Trempe, F., Stanley, M., Bhatti, A. I., et al. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00707-6 · Cited by 5 · see citing works
Evaluation of Pharmacological Rescue of Melanocortin-4 Receptor Nonsense Mutations by Aminoglycoside
Höpfner, F., Zschunke, S., Reininghaus, N., Sohail, I., Scheerer, P., Annibale, P., Biebermann, H., & Kühnen, P. (2022) · Life · doi:10.3390/life12111793 · Cited by 4 · see citing works
“Recently, the efﬁcacy of glucagon-like peptide (GLP)-1 receptor agonist treatment has been evaluated in short-term clinical studies [44].”
Novel Targets in Glucose Homeostasis and Obesity—Lesson from Rare Mutations
Feng, B. C., Xu, P., & He, Y. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01351-7 · Cited by 4 · see citing works
A new era in childhood obesity
Martos‐Moreno, G. Á., Guijo, B., Tena‐Sempere, M., Chowen, J. A., & Argente, J. (2026) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2026.03.006 · Cited by 5 · see citing works
Management of Childhood Obesity
Gad, H., Dauleh, H., Mohammed, I., Malik, R. A., & Hussain, K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27083528 · Cited by 4 · see citing works
Protocol for a randomised, double-blinded, controlled trial of youth with childhood-onset obesity treated with semaglutide 2.4 mg/week: the RESETTLE trial
Byberg, S., Holt, J., Sandsdal, R. M., Holm, L. A., Madsen, L. B., Christensen, B., Jensen, S. B. K., Hansen, T. F., Holm, J., & Torekov, S. S. (2024) · BMJ Open · doi:10.1136/bmjopen-2023-082446 · Cited by 4 · see citing works
“16 24 Thus, GLP-1 RA-based treatment may also facilitate weight loss in youth with insufficient treatment response to non-pharmacological care alone.”
Self-citation
Novel homozygous leptin receptor mutation in an infant with monogenic obesity
Boro, H., Bundela, V., Mannar, V., Nagendra, L., Jain, V., Jain, B., Kumar, S., V, & Agstam, S. (2023) · Pediatric Endocrinology Diabetes and Metabolism · doi:10.5114/pedm.2023.129344 · Cited by 2 · see citing works
“Drugs like GLP-1 analogues (liraglutide in a dose of 3 mg) have been tried in monogenic obesity due to MC4 mutations, but without effective results [32].”
Background
Innovative Care for Children and Adolescents with Severe and/or Genetic Obesity
Schirmer, M., Zorn, S., von Schnurbein, J., & Wabitsch, M. (2025) · Hormone Research in Paediatrics · doi:10.1159/000544177 · Cited by 2 · see citing works
“2 deletions also bene ﬁ t from GLP-1 RA therapy [32 – 34].”

GLP-1 Receptor Agonist Treatment in Morbid Obesity and Type 2 Diabetes Due to Pathogenic Homozygous Melanocortin-4 Receptor Mutation: A Case Report
Iepsen, E. W., Have, C. T., Veedfald, S., Madsbad, S., Holst, J. J., Grarup, N., Pedersen, O., Brandslund, I., Holm, J.-C., Hansen, T., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100006 · Cited by 43 · see citing works
Self-citation
The application of GLP-1 receptor agonists in obesity due to MC4R deficiency
Ding, M., Luo, Y., & Ji, L. (2026) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2026.58
Monogenic Obesity; Using Drugs to Bypass the Problem
Coll, A. P. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.015 · Cited by 28 · see citing works
Patients with obesity caused by melanocortin-4 receptor mutations can be treated with a glucagon-like-peptide-1 receptor agonist, Iepsen EW
Iepsen, E. W. (2018) · Data Archiving and Networked Services (DANS) · doi:10.17632/dryd5vjvz4.1
Self-citation
Treatment Approaches for Obesity in Children With Heterozygous MC4R Variants
Salama, M., Saba, L., Valdez, L., Lteif, A. N., & Kumar, S. (2026) · Clinical Obesity · doi:10.1111/cob.70069

Authors: Iepsen, E. W., Zhang, J., Thomsen, H. S., Hansen, E. L., Hollensted, M., Madsbad, S., Hansen, T., Holst, J. J., Holm, J.-C., & Torekov, S. S.
Affiliations: University of Copenhagen (DK)
Herlev Hospital (DK)
Hvidovre Hospital (DK)
Holbæk Sygehus (DK)
Corresponding author: Iepsen, Eva W.
Torekov, Signe S.
ORCID: Iepsen, Eva W.
Zhang, Jinyi
Thomsen, Henrik S.
Hollensted, Mette
Madsbad, Sten
Hansen, Torben
Holst, Jens J.
Holm, Jens-Christian
Torekov, Signe S.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2018-07
Volume: 28
Issue: 1
Pages: 23-32.e3
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2018.05.008
OpenAlex: W2806545464
Cited by: 156
References: 59
Citations by year: 2026: 18 · 2025: 15 · 2024: 25 · 2023: 24 · 2022: 22 · 2021: 21 · 2020: 22 · 2019: 6 · 2018: 3
FWCI: 7.33
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: Lundbeckfonden
Region Sjælland
Danish Diabetes Academy
Novo Nordisk Fonden
Aase og Ejnar Danielsens Fond (NNF15CC0018486)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: melanocortin-4 receptor, MC4R mutations, monogenic obesity, liraglutide, GLP-1 receptor agonists, weight loss, appetite regulation, fat mass, fasting and postprandial glucose, obesity treatment
MeSH terms: Glucagon-Like Peptide-1 Receptor, Liraglutide, Adult, Appetite, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Mutation, Obesity, Weight Loss, Receptor, Melanocortin, Type 4

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

Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks