Skip to content
naulon

No retraction, correction or concern found when last checked on Oct 30, 2026.

Anti-obesity drug discovery: advances and challenges

Timo D. Müller, Matthias Blüher, Matthias H. Tschöp and 1 more

Nature Reviews Drug Discovery · 2021 · Review

doi:10.1038/s41573-021-00337-8

Abstract

Enormous progress has been made in the last half-century in the management of diseases closely integrated with excess body weight, such as hypertension, adult-onset diabetes and elevated cholesterol. However, the treatment of obesity itself has proven largely resistant to therapy, with anti-obesity medications (AOMs) often delivering insufficient efficacy and dubious safety. Here, we provide an overview of the history of AOM development, focusing on lessons learned and ongoing obstacles. Recent advances, including increased understanding of the molecular gut–brain communication, are inspiring the pursuit of next-generation AOMs that appear capable of safely achieving sizeable and sustained body weight loss. The development of therapies that are capable of safely achieving sizeable and sustained body weight loss has proved tremendously challenging. Here, Müller et al. provide an overview of the history of anti-obesity drug development, focusing on lessons learned, ongoing challenges and recent advances in the field.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 334

  1. 1.
  2. 2.

    Bauer UE, Briss PA, Goodman RA, Bowman BA. Prevention of chronic disease in the 21st century: elimination of the leading preventable causes of premature death and disability in the USA. Lancet. 2014;384:45-52.

    Not in our library10.1016/s0140-6736(14)60648-6

  3. 3.

    Bjerregaard LG, et al. Change in overweight from childhood to early adulthood and risk of type 2 diabetes. N. Engl. J. Med. 2018;378:1302-1312.

    Not in our library10.1056/nejmoa1713231

  4. 4.

    Twig G, et al. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N. Engl. J. Med. 2016;374:2430-2440.

    Not in our library10.1056/nejmoa1503840

  5. 5.

    Berrington de Gonzalez A, et al. Body-mass index and mortality among 1.46 million white adults. N. Engl. J. Med. 2010;363:2211-2219.

    Not in our library10.1056/nejmoa1000367

  6. 6.

    Calle EE. Obesity and cancer. BMJ. 2007;335:1107-1108.

    Not in our library10.1136/bmj.39384.472072.80

  7. 7.

    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 2003;348:1625-1638.

    Not in our library10.1056/nejmoa021423

  8. 8.

    Belanger MJ, et al. Covid-19 and disparities in nutrition and obesity. N. Engl. J. Med. 2020;383:e69.

    Not in our library10.1056/nejmp2021264

  9. 9.

    Arnold M, et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol. 2015;16:36-46.

    Not in our library10.1016/s1470-2045(14)71123-4

  10. 10.

    Arnold M, et al. Obesity and cancer: an update of the global impact. Cancer Epidemiol. 2016;41:8-15.

    Not in our library10.1016/j.canep.2016.01.003

  11. 11.

    Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA. 2003;289:187-193.

    Not in our library10.1001/jama.289.2.187

  12. 12.

    Prospective Studies C, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083-1096.

    Not in our library10.1016/s0140-6736(09)60318-4

  13. 13.

    Ebbeling CB, Pawlak DB, Ludwig DS. Childhood obesity: public-health crisis, common sense cure. Lancet. 2002;360:473-482.

    Not in our library10.1016/s0140-6736(02)09678-2

  14. 14.

    Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. J. Health Econ. 2012;31:219-230.

    Not in our library10.1016/j.jhealeco.2011.10.003

  15. 15.

    McAllister EJ, et al. Ten putative contributors to the obesity epidemic. Crit. Rev. Food Sci. Nutr. 2009;49:868-913.

    Not in our library10.1080/10408390903372599

  16. 16.

    Cappuccio FP, et al. Meta-analysis of short sleep duration and obesity in children and adults. Sleep. 2008;31:619-626.

    Not in our library10.1093/sleep/31.5.619

  17. 17.

    Noh J. The effect of circadian and sleep disruptions on obesity risk. J. Obes. Metab. Syndr. 2018;27:78-83.

    Not in our library10.7570/jomes.2018.27.2.78

  18. 18.

    Scott KA, Melhorn SJ, Sakai RR. Effects of chronic social stress on obesity. Curr. Obes. Rep. 2012;1:16-25.

    Not in our library10.1007/s13679-011-0006-3

  19. 19.

    Ness-Abramof R, Apovian CM. Drug-induced weight gain. Drugs Today. 2005;41:547-555.

    Not in our library10.1358/dot.2005.41.8.893630

  20. 20.

    Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav. Genet. 1997;27:325-351.

    Not in our library10.1023/a:1025635913927

  21. 21.

    Bray MS, et al. NIH working group report — using genomic information to guide weight management: from universal to precision treatment. Obesity. 2016;24:14-22.

    Not in our library10.1002/oby.21381

  22. 22.
  23. 23.

    Grjibovski AM, Olsen AO, Magnus P, Harris JR. Psoriasis in Norwegian twins: contribution of genetic and environmental effects. J. Eur. Acad. Dermatol. Venereol. 2007;21:1337-1343.

    Not in our library10.1111/j.1468-3083.2007.02268.x

  24. 24.

    Katzmarzyk PT, et al. Familial resemblance for coronary heart disease risk: the HERITAGE Family Study. Ethn. Dis. 2000;10:138-147.

    Not in our library

  25. 25.

    Czene K, Lichtenstein P, Hemminki K. Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int. J. Cancer. 2002;99:260-266.

    Not in our library10.1002/ijc.10332

  26. 26.

    Bray GA, Kim KK, Wilding JPH, World Obesity F. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes. Rev. 2017;18:715-723.

    Not in our library10.1111/obr.12551

  27. 27.

    Burki T. European Commission classifies obesity as a chronic disease. Lancet Diabetes Endocrinol. 2021;9:418.

    Not in our library10.1016/s2213-8587(21)00145-5

  28. 28.

    Bluher M. Obesity: global epidemiology and pathogenesis. Nat. Rev. Endocrinol. 2019;15:288-298.

    Not in our library10.1038/s41574-019-0176-8

  29. 29.

    Carlsson LMS, et al. Life expectancy after bariatric surgery in the Swedish Obese Subjects Study. N. Engl. J. Med. 2020;383:1535-1543.

    Not in our library10.1056/nejmoa2002449

  30. 30.

    Adams TD, et al. Weight and metabolic outcomes 12 years after gastric bypass. N. Engl. J. Med. 2017;377:1143-1155.

    Not in our library10.1056/nejmoa1700459

  31. 31.

    Farooqi IS. Defining the neural basis of appetite and obesity: from genes to behaviour. Clin. Med. 2014;14:286-289.

    Not in our library10.7861/clinmedicine.14-3-286

  32. 32.
  33. 33.
  34. 34.

    Muller TD, Clemmensen C, Finan B, DiMarchi RD, Tschop MH. Anti-obesity therapy: from rainbow pills to polyagonists. Pharmacol. Rev. 2018;70:712-746.

    Not in our library10.1124/pr.117.014803

  35. 35.

    Davies M, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397:971-984.

    Not in our library10.1016/s0140-6736(21)00213-0

  36. 36.

    Rubino D, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325:1414-1425.

    Not in our library10.1001/jama.2021.3224

  37. 37.

    Wadden TA, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical tTrial. JAMA. 2021;325:1403-1413.

    Not in our library10.1001/jama.2021.1831

  38. 38.

    Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity. N. Engl. J. Med. 2021;384:989.

    Not in our library10.1056/nejmoa2032183

  39. 39.

    Tak YJ, Lee SY. Anti-obesity drugs: long-term efficacy and safety: an updated review. World J. Mens Health. 2020;39:208-221.

    Not in our library10.5534/wjmh.200010

  40. 40.

    Bray GA, Fruhbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387:1947-1956.

    Not in our library10.1016/s0140-6736(16)00271-3

  41. 41.

    Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N. Engl. J. Med. 2017;376:254-266.

    Not in our library10.1056/nejmra1514009

  42. 42.

    Magkos F, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23:591-601.

    Not in our library10.1016/j.cmet.2016.02.005

  43. 43.

    Knowler WC, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 2002;346:393-403.

    Not in our library10.1056/nejmoa012512

  44. 44.

    Sjostrom L, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N. Engl. J. Med. 2007;357:741-752.

    Not in our library10.1056/nejmoa066254

  45. 45.
  46. 46.

    Stefan N, Haring HU, Schulze MB. Metabolically healthy obesity: the low-hanging fruit in obesity treatment? Lancet Diabetes Endocrinol. 2018;6:249-258.

    Not in our library10.1016/s2213-8587(17)30292-9

  47. 47.

    Zhang Y, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425-432.

    Not in our library10.1038/372425a0

  48. 48.

    Adriaenssens AE, Gribble FM, Reimann F. The glucose-dependent insulinotropic polypeptide signaling axis in the central nervous system. Peptides. 2020;125:170194.

    Not in our library10.1016/j.peptides.2019.170194

  49. 49.

    Farooqi IS. Monogenic human obesity. Front. Horm. Res. 2008;36:1-11.

    Not in our library10.1159/000115333

  50. 50.

    Farooqi IS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 2003;348:1085-1095.

    Not in our library10.1056/nejmoa022050

  51. 51.

    Farooqi, I. S. & O’Rahilly, S. The Genetics of Obesity in Humans (Endotext, 2000).

    Not in our library10.1210/er.2006-0040

  52. 52.

    Kushner RF, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP Trials 1 to 5. Obesity. 2020;28:1050-1061.

    Not in our library10.1002/oby.22794

  53. 53.

    O’Neil PM, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392:637-649.

    Not in our library10.1016/s0140-6736(18)31773-2

  54. 54.

    Tainter ML, Cutting WC, Stockton AB. Use of dinitrophenol in nutritional disorders: a critical survey of clinical results. Am. J. Public. Health Nations Health. 1934;24:1045-1053.

    Not in our library10.2105/ajph.24.10.1045

  55. 55.

    Tainter ML, Stockton AB, Cutting WC. Use of dinitrophenol in obesity and related conditions. JAMA. 1933;101:1472-1475.

    Not in our library10.1001/jama.1933.02740440032009

  56. 56.

    Dunlop DM. The use of 2:4-dinitrophenol as a metabolic stimulant. Br. Med. J. 1934;3820:524.

    Not in our library10.1136/bmj.1.3820.524

  57. 57.

    Alphin RS, Ward JW. Anorexigenic effects of fenfluramine hydrochloride in rats, guinea pigs, and dogs. Toxicol. Appl. Pharmacol. 1969;14:182-191.

    Not in our library10.1016/0041-008x(69)90178-1

  58. 58.

    Pinder RM, Brogden RN, Sawyer PR, Speight TM, Avery GS. Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. Drugs. 1975;10:241-323.

    Not in our library10.2165/00003495-197510040-00001

  59. 59.

    Weintraub M, et al. Long-term weight control study. I (weeks 0 to 34). The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin. Pharmacol. Ther. 1992;51:586-594.

    Not in our library10.1038/clpt.1992.69

  60. 60.

    Finer N, Craddock D, Lavielle R, Keen H. Effect of 6 months therapy with dexfenfluramine in obese patients: studies in the United Kingdom. Clin. Neuropharmacol. 1988;11:S179-186.

    Not in our library

  61. 61.

    Khera R, et al. Effect of dexfenfluramine on eating behavior and body weight of obese patients: results of a field study of isomeride in Austrian general practice [German]. Acta Med. Austriaca. 1995;22:95-101.

    Not in our library

  62. 62.

    Holdaway IM, Wallace E, Westbrooke L, Gamble G. Effect of dexfenfluramine on body weight, blood pressure, insulin resistance and serum cholesterol in obese individuals. Int. J. Obes. Relat. Metab. Disord. 1995;19:749-751.

    Not in our library

  63. 63.

    Andersen T, Astrup A, Quaade F. Dexfenfluramine as adjuvant to a low-calorie formula diet in the treatment of obesity: a randomized clinical trial. Int. J. Obes. Relat. Metab. Disord. 1992;16:35-40.

    Not in our library

  64. 64.

    Khera R, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315:2424-2434.

    Not in our library10.1001/jama.2016.7602

  65. 65.

    Smith SR, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N. Engl. J. Med. 2010;363:245-256.

    Not in our library10.1056/nejmoa0909809

  66. 66.

    Davidson MH, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281:235-242.

    Not in our library10.1001/jama.281.3.235

  67. 67.

    Despres JP, Golay A, Sjostrom L, Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N. Engl. J. Med. 2005;353:2121-2134.

    Not in our library10.1056/nejmoa044537

  68. 68.

    Pi-Sunyer FX, et al. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 2006;295:761-775.

    Not in our library10.1001/jama.295.7.761

  69. 69.

    Van Gaal LF, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005;365:1389-1397.

    Not in our library10.1016/s0140-6736(05)66374-x

  70. 70.

    Bray GA. A concise review on the therapeutics of obesity. Nutrition. 2000;16:953-960.

    Not in our library10.1016/s0899-9007(00)00424-x

  71. 71.

    Ioannides-Demos LL, Proietto J, McNeil JJ. Pharmacotherapy for obesity. Drugs. 2005;65:1391-1418.

    Not in our library10.2165/00003495-200565100-00006

  72. 72.

    Antel J, Hebebrand J. Weight-reducing side effects of the antiepileptic agents topiramate and zonisamide. Handb. Exp. Pharmacol. 2012;209:433-466.

    Not in our library10.1007/978-3-642-24716-3_20

  73. 73.

    Walter CP, Bleske BE, Dorsch MP. Pharmacotherapy for weight loss: the cardiovascular effects of the old and new agents. J. Clin. Pharm. Ther. 2014;39:475-484.

    Not in our library10.1111/jcpt.12177

  74. 74.
  75. 75.

    Nissen SE, et al. Effect of naltrexone–bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomized clinical trial. JAMA. 2016;315:990-1004.

    Not in our library10.1001/jama.2016.1558

  76. 76.

    Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 2016;375:311-322.

    Not in our library10.1056/nejmoa1603827

  77. 77.

    Astrup A, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int. J. Obes. 2012;36:843-854.

    Not in our library10.1038/ijo.2011.158

  78. 78.

    Farooqi IS, O’Rahilly S. Monogenic human obesity syndromes. Recent. Prog. Horm. Res. 2004;59:409-424.

    Not in our library10.1210/rp.59.1.409

  79. 79.

    Hebebrand J, Sommerlad C, Geller F, Gorg T, Hinney A. The genetics of obesity: practical implications. Int. J. Obes. Relat. Metab. Disord. 2001;25:S10-18.

    Not in our library10.1038/sj.ijo.0801689

  80. 80.

    Li L, et al. Identification of type 2 diabetes subgroups through topological analysis of patient similarity. Sci. Transl Med. 2015;7:311ra174.

    Not in our library10.1126/scitranslmed.aaa9364

  81. 81.

    Lyssenko V, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N. Engl. J. Med. 2008;359:2220-2232.

    Not in our library10.1056/nejmoa0801869

  82. 82.

    O’Rahilly S. Human genetics illuminates the paths to metabolic disease. Nature. 2009;462:307-314.

    Not in our library10.1038/nature08532

  83. 83.
  84. 84.

    Ahlqvist E, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018;6:361-369.

    Not in our library10.1016/s2213-8587(18)30051-2

  85. 85.

    Chatterjee S, Davies MJ. Accurate diagnosis of diabetes mellitus and new paradigms of classification. Nat. Rev. Endocrinol. 2018;14:386-387.

    Not in our library10.1038/s41574-018-0025-1

  86. 86.
  87. 87.

    Fall T, Ingelsson E. Genome-wide association studies of obesity and metabolic syndrome. Mol. Cell Endocrinol. 2014;382:740-757.

    Not in our library10.1016/j.mce.2012.08.018

  88. 88.

    Farooqi S, O’Rahilly S. Genetics of obesity in humans. Endocr. Rev. 2006;27:710-718.

    Not in our library10.1210/er.2006-0040

  89. 89.

    Locke AE, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197-206.

    Not in our library10.1038/nature14177

  90. 90.

    Rankinen T, et al. The human obesity gene map: the 2005 update. Obesity. 2006;14:529-644.

    Not in our library10.1038/oby.2006.71

  91. 91.

    Huypens P, et al. Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nat. Genet. 2016;48:497-499.

    Not in our library10.1038/ng.3527

  92. 92.

    Dong C, et al. Possible genomic imprinting of three human obesity-related genetic loci. Am. J. Hum. Genet. 2005;76:427-437.

    Not in our library10.1086/428438

  93. 93.

    Hoggart CJ, et al. Novel approach identifies SNPs in SLC2A10 and KCNK9 with evidence for parent-of-origin effect on body mass index. PLoS Genet. 2014;10:e1004508.

    Not in our library10.1371/journal.pgen.1004508

  94. 94.

    Melvin A, O’Rahilly S, Savage DB. Genetic syndromes of severe insulin resistance. Curr. Opin. Genet. Dev. 2018;50:60-67.

    Not in our library10.1016/j.gde.2018.02.002

  95. 95.

    Farooqi IS, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 2002;110:1093-1103.

    Not in our library10.1172/jci0215693

  96. 96.

    Gibson WT, et al. Congenital leptin deficiency due to homozygosity for the Δ133G mutation: report of another case and evaluation of response to four years of leptin therapy. J. Clin. Endocrinol. Metab. 2004;89:4821-4826.

    Not in our library10.1210/jc.2004-0376

  97. 97.

    Montague CT, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387:903-908.

    Not in our library10.1038/43185

  98. 98.

    Farooqi IS, et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N. Engl. J. Med. 2007;356:237-247.

    Not in our library10.1056/nejmoa063988

  99. 99.

    Krude H, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 1998;19:155-157.

    Not in our library10.1038/509

  100. 100.

    Farooqi IS, et al. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J. Clin. Invest. 2000;106:271-279.

    Not in our library10.1172/jci9397

  101. 101.

    Frayling TM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889-894.

    Not in our library10.1126/science.1141634

  102. 102.

    Hinney A, Volckmar AL, Knoll N. Melanocortin-4 receptor in energy homeostasis and obesity pathogenesis. Prog. Mol. Biol. Transl. Sci. 2013;114:147-191.

    Not in our library10.1016/b978-0-12-386933-3.00005-4

  103. 103.

    Friedman JM. A war on obesity, not the obese. Science. 2003;299:856-858.

    Not in our library10.1126/science.1079856

  104. 104.

    Friedman JM. Modern science versus the stigma of obesity. Nat. Med. 2004;10:563-569.

    Not in our library10.1038/nm0604-563

  105. 105.

    Friedman JM. Obesity: causes and control of excess body fat. Nature. 2009;459:340-342.

    Not in our library10.1038/459340a

  106. 106.

    Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395:763-770.

    Not in our library10.1038/27376

  107. 107.

    Kraschnewski JL, et al. Long-term weight loss maintenance in the United States. Int. J. Obes. 2010;34:1644-1654.

    Not in our library10.1038/ijo.2010.94

  108. 108.

    Leibel RL, et al. Biologic responses to weight loss and weight regain: report from an American Diabetes Association Research Symposium. Diabetes. 2015;64:2299-2309.

    Not in our library10.2337/db15-0004

  109. 109.

    Lowe MR, Miller-Kovach K, Phelan S. Weight-loss maintenance in overweight individuals one to five years following successful completion of a commercial weight loss program. Int. J. Obes. Relat. Metab. Disord. 2001;25:325-331.

    Not in our library10.1038/sj.ijo.0801521

  110. 110.

    Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology’s response to dieting: the impetus for weight regain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011;301:R581-R600.

    Not in our library10.1152/ajpregu.00755.2010

  111. 111.

    Korner J, Savontaus E, Chua SC, Leibel RL, Wardlaw SL. Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus. J. Neuroendocrinol. 2001;13:959-966.

    Not in our library10.1046/j.1365-2826.2001.00716.x

  112. 112.

    Levin BE, Dunn-Meynell AA. Chronic exercise lowers the defended body weight gain and adiposity in diet-induced obese rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004;286:R771-R778.

    Not in our library10.1152/ajpregu.00650.2003

  113. 113.

    Yu Y, South T, Wang Q, Huang XF. Differential expression of hypothalamic CART mRNA in response to body weight change following different dietary interventions. Neurochem. Int. 2008;52:1422-1430.

    Not in our library10.1016/j.neuint.2008.03.003

  114. 114.

    Cabral A, et al. Fasting induces remodeling of the orexigenic projections from the arcuate nucleus to the hypothalamic paraventricular nucleus, in a growth hormone secretagogue receptor-dependent manner. Mol. Metab. 2020;32:69-84.

    Not in our library10.1016/j.molmet.2019.11.014

  115. 115.

    Heymsfield SB, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA. 1999;282:1568-1575.

    Not in our library10.1001/jama.282.16.1568

  116. 116.

    Hukshorn CJ, et al. Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J. Clin. Endocrinol. Metab. 2000;85:4003-4009.

    Not in our library10.1210/jcem.85.11.6955

  117. 117.

    Scarpace PJ, Zhang Y. Leptin resistance: a prediposing factor for diet-induced obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009;296:R493-R500.

    Not in our library10.1152/ajpregu.90669.2008

  118. 118.

    Farooqi IS, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med. 1999;341:879-884.

    Not in our library10.1056/nejm199909163411204

  119. 119.

    von Schnurbein J, et al. Rapid improvement of hepatic steatosis after initiation of leptin substitution in a leptin-deficient girl. Horm. Res. Paediatr. 2013;79:310-317.

    Not in our library10.1159/000348541

  120. 120.

    Heal D, Gosden J, Smith S. The 5-HT6 receptor as a target for developing novel antiobesity drugs. Int. Rev. Neurobiol. 2011;96:73-109.

    Not in our library10.1016/b978-0-12-385902-0.00004-8

  121. 121.

    Vickers SP, Jackson HC, Cheetham SC. The utility of animal models to evaluate novel anti-obesity agents. Br. J. Pharmacol. 2011;164:1248-1262.

    Not in our library10.1111/j.1476-5381.2011.01245.x

  122. 122.

    Coskun T, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol. Metab. 2018;18:3-14.

    Not in our library10.1016/j.molmet.2018.09.009

  123. 123.

    Gabery S, et al. Semaglutide lowers body weight in rodents via distributed neural pathways. JCI Insight. 2020;5:e133429.

    Not in our library10.1172/jci.insight.133429

  124. 124.

    Frias JP, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392:2180-2193.

    Not in our library10.1016/s0140-6736(18)32260-8

  125. 125.

    Frias JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N. Engl. J. Med. 2021;385:503-515.

    Not in our library10.1056/nejmoa2107519

  126. 126.

    Ludvik B, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398:583-598.

    Not in our library10.1016/s0140-6736(21)01443-4

  127. 127.

    Rosenstock J, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398:143-155.

    Not in our library10.1016/s0140-6736(21)01324-6

  128. 128.

    Tschop MH, et al. A guide to analysis of mouse energy metabolism. Nat. Methods. 2011;9:57-63.

    Not in our library10.1038/nmeth.1806

  129. 129.

    Wing RR, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011;34:1481-1486.

    Not in our library10.2337/dc10-2415

  130. 130.

    Muller TD, et al. Glucagon-like peptide 1 (GLP-1). Mol. Metab. 2019;30:72-130.

    Not in our library10.1016/j.molmet.2019.09.010

  131. 131.

    Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat. Rev. Endocrinol. 2012;8:728-742.

    Not in our library10.1038/nrendo.2012.140

  132. 132.

    Khera R, et al. Effects of weight-loss medications on cardiometabolic risk profiles: a systematic review and network meta-analysis. Gastroenterology. 2018;154:1309-1319.e7.

    Not in our library10.1053/j.gastro.2017.12.024

  133. 133.

    Dostalova I, Haluzikova D, Haluzik M. Fibroblast growth factor 21: a novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus. Physiol. Res. 2009;58:1-7.

    Not in our library10.33549/physiolres.931610

  134. 134.

    Talukdar S, et al. A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects. Cell Metab. 2016;23:427-440.

    Not in our library10.1016/j.cmet.2016.02.001

  135. 135.

    Kim AM, et al. Once-weekly administration of a long-acting fibroblast growth factor 21 analogue modulates lipids, bone turnover markers, blood pressure and body weight differently in obese people with hypertriglyceridaemia and in non-human primates. Diabetes Obes. Metab. 2017;19:1762-1772.

    Not in our library10.1111/dom.13023

  136. 136.

    Farooqi IS, O’Rahilly S. Monogenic obesity in humans. Annu. Rev. Med. 2005;56:443-458.

    Not in our library10.1146/annurev.med.56.062904.144924

  137. 137.

    Lejeune MP, Hukshorn CJ, Saris WH, Westerterp-Plantenga MS. Effect of dietary restraint during and following pegylated recombinant leptin (PEG-OB) treatment of overweight men. Int. J. Obes. Relat. Metab. Disord. 2003;27:1494-1499.

    Not in our library10.1038/sj.ijo.0802431

  138. 138.

    Zelissen PM, et al. Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial. Diabetes Obes. Metab. 2005;7:755-761.

    Not in our library10.1111/j.1463-1326.2005.00468.x

  139. 139.
  140. 140.
  141. 141.

    Ryan DH, et al. Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design. Am. Heart J. 2020;229:61-69.

    Not in our library10.1016/j.ahj.2020.07.008

  142. 142.

    Mladenka P, et al. Comprehensive review of cardiovascular toxicity of drugs and related agents. Med. Res. Rev. 2018;38:1332-1403.

    Not in our library10.1002/med.21476

  143. 143.

    Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann. Intern. Med. 2005;143:380-385.

    Not in our library10.7326/0003-4819-143-5-200509060-00013

  144. 144.

    Hendricks EJ, Greenway FL, Westman EC, Gupta AK. Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity. 2011;19:2351-2360.

    Not in our library10.1038/oby.2011.94

  145. 145.

    Kang JG, Park CY, Kang JH, Park YW, Park SW. Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity. Diabetes Obes. Metab. 2010;12:876-882.

    Not in our library10.1111/j.1463-1326.2010.01242.x

  146. 146.

    Hadden DR, Lucey C. Diethylpropion in the treatment of obesity. A cross-over trial of a long-acting preparation. Ulst. Med. J. 1961;30:109-113.

    Not in our library

  147. 147.

    Nash J. The treatment of obesity by control of appetite with diethylproprion (Tenuate). J. Ir. Med. Assoc. 1961;48:15-17.

    Not in our library

  148. 148.

    Seaton DA, Duncan LJ, Rose K, Scott AM. Diethyl-propion in the treatment of “refractory” obesity. Br. Med. J. 1961;1:1009-1011.

    Not in our library10.1136/bmj.1.5231.1009

  149. 149.

    Wilson R, Long C. A clinical evaluation of Tenuate — a new anti-appetite compound. J. Ir. Med. Assoc. 1960;46:86-88.

    Not in our library

  150. 150.

    Cannistra LB, Davis SM, Bauman AG. Valvular heart disease associated with dexfenfluramine. N. Engl. J. Med. 1997;337:636.

    Not in our library10.1056/nejm199708283370912

  151. 151.

    Centers for Disease Control and Prevention. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997. MMWR Morb. Mortal. Wkly. Rep. 46, 1061–1066 (1997).

    Not in our library

  152. 152.

    Connolly HM, et al. Valvular heart disease associated with fenfluramine–phentermine. N. Engl. J. Med. 1997;337:581-588.

    Not in our library10.1056/nejm199708283370901

  153. 153.

    Hayes JF, Bhaskaran K, Batterham R, Smeeth L, Douglas I. The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom. Int. J. Obes. 2015;39:1359-1364.

    Not in our library10.1038/ijo.2015.86

  154. 154.

    James WP, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N. Engl. J. Med. 2010;363:905-917.

    Not in our library10.1056/nejmoa1003114

  155. 155.

    Zhou YH, et al. Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials. PLoS ONE. 2012;7:e39062.

    Not in our library10.1371/journal.pone.0039062

  156. 156.

    Seimon RV, et al. Changes in body weight and pulse: outcome events in overweight and obese subjects with cardiovascular disease in the SCOUT trial. Int. J. Obes. 2015;39:849-857.

    Not in our library10.1038/ijo.2014.211

  157. 157.

    Fujioka K, et al. Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Diabetes Obes. Metab. 2000;2:175-187.

    Not in our library10.1046/j.1463-1326.2000.00081.x

  158. 158.

    McMahon FG, et al. Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial. Arch. Intern. Med. 2000;160:2185-2191.

    Not in our library10.1001/archinte.160.14.2185

  159. 159.

    Wooltorton E. Obesity drug sibutramine (Meridia): hypertension and cardiac arrhythmias. CMAJ. 2002;166:1307-1308.

    Not in our library

  160. 160.

    Yanovski SZ, Yanovski JA. Obesity. N. Engl. J. Med. 2002;346:591-602.

    Not in our library10.1056/nejmra012586

  161. 161.

    Marso SP, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2016;375:1834-1844.

    Not in our library10.1056/nejmoa1607141

  162. 162.

    Kleinert M, et al. Animal models of obesity and diabetes mellitus. Nat. Rev. Endocrinol. 2018;14:140-162.

    Not in our library10.1038/nrendo.2017.161

  163. 163.

    Elangbam CS. Review paper: Current strategies in the development of anti-obesity drugs and their safety concerns. Vet. Pathol. 2009;46:10-24.

    Not in our library10.1354/vp.46-1-10

  164. 164.

    Arch JR. Horizons in the pharmacotherapy of obesity. Curr. Obes. Rep. 2015;4:451-459.

    Not in our library10.1007/s13679-015-0177-4

  165. 165.

    Srivastava G, Apovian C. Future pharmacotherapy for obesity: new anti-obesity drugs on the horizon. Curr. Obes. Rep. 2018;7:147-161.

    Not in our library10.1007/s13679-018-0300-4

  166. 166.

    Wharton S, Serodio KJ. Next generation of weight management medications: implications for diabetes and CVD risk. Curr. Cardiol. Rep. 2015;17:35.

    Not in our library10.1007/s11886-015-0590-z

  167. 167.

    Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes — state-of-the-art. Mol. Metab. 2021;46:101102.

    Not in our library10.1016/j.molmet.2020.101102

  168. 168.

    Seino Y, Rasmussen MF, Zdravkovic M, Kaku K. Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: a double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes. Diabetes Res. Clin. Pract. 2008;81:161-168.

    Not in our library10.1016/j.diabres.2008.03.018

  169. 169.

    Vilsboll T, et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care. 2007;30:1608-1610.

    Not in our library10.2337/dc06-2593

  170. 170.

    Ponzani P, Scardapane M, Nicolucci A, Rossi MC. Effectiveness and safety of liraglutide after three years of treatment. Minerva Endocrinol. 2016;41:35-42.

    Not in our library

  171. 171.

    Vilsboll T, Krarup T, Madsbad S, Holst JJ. No reactive hypoglycaemia in type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose. Diabet. Med. 2001;18:144-149.

    Not in our library10.1046/j.1464-5491.2001.00424.x

  172. 172.

    Nauck MA, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J. Clin. Endocrinol. Metab. 2002;87:1239-1246.

    Not in our library10.1210/jcem.87.3.8355

  173. 173.

    Goldsmith F, et al. Induction of energy expenditure by sitagliptin is dependent on GLP-1 receptor. PLoS ONE. 2015;10:e0126177.

    Not in our library10.1371/journal.pone.0126177

  174. 174.

    Gallwitz B, et al. Sitagliptin: profile of a novel DPP-4 inhibitor for the treatment of type 2 diabetes. Drugs Today. 2007;43:13-25.

    Not in our library10.1358/dot.2007.43.1.1043909

  175. 175.

    Huthmacher JA, Meier JJ, Nauck MA. Efficacy and safety of short- and long-acting glucagon-like peptide 1 receptor agonists on a background of basal insulin in type 2 diabetes: a meta-analysis. Diabetes Care. 2020;43:2303-2312.

    Not in our library10.2337/dc20-0498

  176. 176.

    Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N. Engl. J. Med. 2015;373:11-22.

    Not in our library10.1056/nejmoa1411892

  177. 177.

    Marso SP, et al. Effects of liraglutide on cardiovascular outcomes in patients with diabetes with or without heart failure. J. Am. Coll. Cardiol. 2020;75:1128-1141.

    Not in our library10.1016/j.jacc.2019.12.063

  178. 178.

    Buckley ST, et al. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci. Transl Med. 2018;10:eaar7047.

    Not in our library10.1126/scitranslmed.aar7047

  179. 179.

    Nauck MA. Preserved incretin activity of glucagon-like peptide 1 [7–36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J. Clin. Invest. 1993;91:301-307.

    Not in our library10.1172/jci116186

  180. 180.

    Chan JL, Roth JD, Weyer C. It takes two to tango: combined amylin/leptin agonism as a potential approach to obesity drug development. J. Investig. Med. 2009;57:777-783.

    Not in our library10.2310/jim.0b013e3181b91911

  181. 181.

    Roth JD, et al. Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc. Natl Acad. Sci. USA. 2008;105:7257-7262.

    Not in our library10.1073/pnas.0706473105

  182. 182.

    Trevaskis JL, et al. Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology. 2008;149:5679-5687.

    Not in our library10.1210/en.2008-0770

  183. 183.

    Cavaco M, Castanho MARB, Neves V. Peptibodies: an elegant solution for a long-standing problem. Pept. Sci. 2018;110:e23095.

    Not in our library10.1002/bip.23095

  184. 184.

    Mroz PA, et al. Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism. Mol. Metab. 2019;20:51-62.

    Not in our library10.1016/j.molmet.2018.12.001

  185. 185.
  186. 186.
  187. 187.

    Dowsett GKC, et al. A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing. Mol. Metab. 2021;53:101240.

    Not in our library10.1016/j.molmet.2021.101240

  188. 188.

    Day JW, et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat. Chem. Biol. 2009;5:749-757.

    Not in our library10.1038/nchembio.209

  189. 189.

    Finan B, et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci. Transl Med. 2013;5:209ra151.

    Not in our library10.1126/scitranslmed.3007218

  190. 190.

    Hayes MR, Borner T, De Jonghe BC. The role of GIP in the regulation of GLP-1 satiety and nausea. Diabetes. 2021;70:1956-1961.

    Not in our library10.2337/dbi21-0004

  191. 191.

    Hojberg PV, et al. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia. 2009;52:199-207.

    Not in our library10.1007/s00125-008-1195-5

  192. 192.

    Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol. Metab. 2020;31:410-421.

    Not in our library10.1016/j.tem.2020.02.006

  193. 193.

    Frias JP, et al. The sustained effects of a dual GIP/GLP-1 receptor agonist, NNC0090-2746, in patients with type 2 diabetes. Cell Metab. 2017;26:343-352.e2.

    Not in our library10.1016/j.cmet.2017.07.011

  194. 194.

    Frias JP, et al. Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens. Diabetes Obes. Metab. 2020;22:938-946.

    Not in our library10.1111/dom.13979

  195. 195.

    DiMarchi RD. “Let’s Stay Together”; GIP and GLP-1 dual agonism in the treatment of metabolic disease. Mol. Metab. 2018;18:1-2.

    Not in our library10.1016/j.molmet.2018.10.004

  196. 196.

    Min T, Bain SC. The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2 diabetes: the SURPASS clinical trials. Diabetes Ther. 2021;12:143-157.

    Not in our library10.1007/s13300-020-00981-0

  197. 197.
  198. 198.

    Nahra R, et al. Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes: a 54-week randomized phase 2b study. Diabetes Care. 2021;44:1433-1442.

    Not in our library10.2337/dc20-2151

  199. 199.

    Eriksson O, et al. Receptor occupancy of dual glucagon-like peptide 1/glucagon receptor agonist SAR425899 in individuals with type 2 diabetes. Sci. Rep. 2020;10:16758.

    Not in our library10.1038/s41598-020-73815-5

  200. 200.

    Tillner J, et al. A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: results of randomized, placebo-controlled first-in-human and first-in-patient trials. Diabetes Obes. Metab. 2019;21:120-128.

    Not in our library10.1111/dom.13494

  201. 201.

    Visentin R, et al. Dual glucagon-like peptide-1 receptor/glucagon receptor agonist SAR425899 improves β-cell function in type 2 diabetes. Diabetes Obes. Metab. 2020;22:640-647.

    Not in our library10.1111/dom.13939

  202. 202.

    Kleinert M, et al. Emerging poly-agonists for obesity and type 2 diabetes. Obesity. 2017;25:1647-1649.

    Not in our library10.1002/oby.21932

  203. 203.

    Trevaskis JL, et al. Interaction of leptin and amylin in the long-term maintenance of weight loss in diet-induced obese rats. Obesity. 2010;18:21-26.

    Not in our library10.1038/oby.2009.187

  204. 204.

    Turek VF, et al. Mechanisms of amylin/leptin synergy in rodent models. Endocrinology. 2010;151:143-152.

    Not in our library10.1210/en.2009-0546

  205. 205.

    Muller TD, et al. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. J. Pept. Sci. 2012;18:383-393.

    Not in our library10.1002/psc.2408

  206. 206.

    Bello NT, Kemm MH, Ofeldt EM, Moran TH. Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2010;299:R945-R952.

    Not in our library10.1152/ajpregu.00275.2010

  207. 207.

    Neary NM, et al. Peptide YY3–36 and glucagon-like peptide-17–36 inhibit food intake additively. Endocrinology. 2005;146:5120-5127.

    Not in our library10.1210/en.2005-0237

  208. 208.

    Trevaskis JL, et al. Synergistic metabolic benefits of an exenatide analogue and cholecystokinin in diet-induced obese and leptin-deficient rodents. Diabetes Obes. Metab. 2015;17:61-73.

    Not in our library10.1111/dom.12390

  209. 209.

    Clemmensen C, et al. Dual melanocortin-4 receptor and GLP-1 receptor agonism amplifies metabolic benefits in diet-induced obese mice. EMBO Mol. Med. 2015;7:288-298.

    Not in our library10.15252/emmm.201404508

  210. 210.

    Finan B, et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat. Med. 2015;21:27-36.

    Not in our library10.1038/nm.3761

  211. 211.

    Tschop MH, et al. Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metab. 2016;24:51-62.

    Not in our library10.1016/j.cmet.2016.06.021

  212. 212.

    Coskun, T. et al. The novel GIP, GLP-1, and glucagon triple receptor agonist LY3437943 exhibits robust efficacy in preclinical models of obesity and diabetes. In American Diabetes Association 81st Scientific Sessions (American Diabetes Association, 2021).

    Not in our library

  213. 213.

    Hebebrand J, Muller TD, Holtkamp K, Herpertz-Dahlmann B. The role of leptin in anorexia nervosa: clinical implications. Mol. Psychiatry. 2007;12:23-35.

    Not in our library10.1038/sj.mp.4001909

  214. 214.

    Chou SH, et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc. Natl Acad. Sci. USA. 2011;108:6585-6590.

    Not in our library10.1073/pnas.1015674108

  215. 215.

    Welt CK, et al. Recombinant human leptin in women with hypothalamic amenorrhea. N. Engl. J. Med. 2004;351:987-997.

    Not in our library10.1056/nejmoa040388

  216. 216.

    Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat. Genet. 1996;12:318-320.

    Not in our library10.1038/ng0396-318

  217. 217.

    Licinio J, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc. Natl Acad. Sci. USA. 2004;101:4531-4536.

    Not in our library10.1073/pnas.0308767101

  218. 218.

    Milos G, et al. Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects. Transl. Psychiatry. 2020;10:303.

    Not in our library10.1038/s41398-020-00977-1

  219. 219.

    Chan JL, et al. Immunogenicity associated with metreleptin treatment in patients with obesity or lipodystrophy. Clin. Endocrinol. 2016;85:137-149.

    Not in our library10.1111/cen.12980

  220. 220.

    Ravussin E, et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity. 2009;17:1736-1743.

    Not in our library10.1038/oby.2009.184

  221. 221.

    Clemmensen C, et al. GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet. Diabetes. 2014;63:1422-1427.

    Not in our library10.2337/db13-1609

  222. 222.

    Liu J, Lee J, Salazar Hernandez MA, Mazitschek R, Ozcan U. Treatment of obesity with celastrol. Cell. 2015;161:999-1011.

    Not in our library10.1016/j.cell.2015.05.011

  223. 223.

    Lee J, et al. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice. Nat. Med. 2016;22:1023-1032.

    Not in our library10.1038/nm.4145

  224. 224.

    Sharma S, et al. Current mechanistic and pharmacodynamic understanding of melanocortin-4 receptor activation. Molecules. 2019;24:1892.

    Not in our library10.3390/molecules24101892

  225. 225.

    Van der Ploeg LH, et al. A role for the melanocortin 4 receptor in sexual function. Proc. Natl Acad. Sci. USA. 2002;99:11381-11386.

    Not in our library10.1073/pnas.172378699

  226. 226.
  227. 227.

    Kievit P, et al. Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques. Diabetes. 2013;62:490-497.

    Not in our library10.2337/db12-0598

  228. 228.

    Kuhnen P, et al. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N. Engl. J. Med. 2016;375:240-246.

    Not in our library10.1056/nejmoa1512693

  229. 229.

    Clement K, et al. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Nat. Med. 2018;24:551-555.

    Not in our library10.1038/s41591-018-0015-9

  230. 230.

    Clement K, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol. 2020;8:960-970.

    Not in our library10.1016/s2213-8587(20)30364-8

  231. 231.

    Lutz TA. Control of food intake and energy expenditure by amylin — therapeutic implications. Int. J. Obes. 2009;33(Suppl 1):S24-S27.

    Not in our library10.1038/ijo.2009.13

  232. 232.

    Young A, Denaro M. Roles of amylin in diabetes and in regulation of nutrient load. Nutrition. 1998;14:524-527.

    Not in our library10.1016/s0899-9007(98)00044-6

  233. 233.

    Boyle CN, Lutz TA, Le Foll C. Amylin — its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity. Mol. Metab. 2018;8:203-210.

    Not in our library10.1016/j.molmet.2017.11.009

  234. 234.

    Ling W, Huang YM, Qiao YC, Zhang XX, Zhao HL. Human amylin: from pathology to physiology and pharmacology. Curr. Protein Pept. Sci. 2019;20:944-957.

    Not in our library10.2174/1389203720666190328111833

  235. 235.

    Bower RL, Hay DL. Amylin structure–function relationships and receptor pharmacology: implications for amylin mimetic drug development. Br. J. Pharmacol. 2016;173:1883-1898.

    Not in our library10.1111/bph.13496

  236. 236.

    Hollander P, et al. Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obes. Res. 2004;12:661-668.

    Not in our library10.1038/oby.2004.76

  237. 237.

    Srivastava G, Apovian CM. Current pharmacotherapy for obesity. Nat. Rev. Endocrinol. 2018;14:12-24.

    Not in our library10.1038/nrendo.2017.122

  238. 238.

    Gydesen S, et al. Optimization of tolerability and efficacy of the novel dual amylin and calcitonin receptor agonist KBP-089 through dose escalation and combination with a GLP-1 analog. Am. J. Physiol. Endocrinol. Metab. 2017;313:E598-E607.

    Not in our library10.1152/ajpendo.00419.2016

  239. 239.

    Bailey RJ, et al. Pharmacological characterization of rat amylin receptors: implications for the identification of amylin receptor subtypes. Br. J. Pharmacol. 2012;166:151-167.

    Not in our library10.1111/j.1476-5381.2011.01717.x

  240. 240.

    Gydesen S, et al. KBP-088, a novel DACRA with prolonged receptor activation, is superior to davalintide in terms of efficacy on body weight. Am. J. Physiol. Endocrinol. Metab. 2016;310:E821-E827.

    Not in our library10.1152/ajpendo.00514.2015

  241. 241.

    Hjuler ST, Andreassen KV, Gydesen S, Karsdal MA, Henriksen K. KBP-042 improves bodyweight and glucose homeostasis with indices of increased insulin sensitivity irrespective of route of administration. Eur. J. Pharmacol. 2015;762:229-238.

    Not in our library10.1016/j.ejphar.2015.05.051

  242. 242.

    Mack CM, et al. Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight. Int. J. Obes. 2010;34:385-395.

    Not in our library10.1038/ijo.2009.238

  243. 243.

    Enebo LB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397:1736-1748.

    Not in our library10.1016/s0140-6736(21)00845-x

  244. 244.

    Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000;407:908-913.

    Not in our library10.1038/35038090

  245. 245.
    Ghrelin · 2015
    No notice
  246. 246.

    Shearman LP, et al. Ghrelin neutralization by a ribonucleic acid-SPM ameliorates obesity in diet-induced obese mice. Endocrinology. 2006;147:1517-1526.

    Not in our library10.1210/en.2005-0993

  247. 247.

    Barnett BP, et al. Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor. Science. 2010;330:1689-1692.

    Not in our library10.1126/science.1196154

  248. 248.

    Kjeldsen-Kragh J, Hvatum M, Haugen M, Forre O, Scott H. Antibodies against dietary antigens in rheumatoid arthritis patients treated with fasting and a one-year vegetarian diet. Clin. Exp. Rheumatol. 1995;13:167-172.

    Not in our library

  249. 249.

    Haqq AM, et al. Ghrelin concentrations in Prader–Willi syndrome (PWS) infants and children: changes during development. Clin. Endocrinol. 2008;69:911-920.

    Not in our library10.1111/j.1365-2265.2008.03385.x

  250. 250.

    Allas S, et al. AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader–Willi syndrome: a randomized placebo-controlled trial. PLoS ONE. 2018;13:e0190849.

    Not in our library10.1371/journal.pone.0190849

  251. 251.

    Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Mol. Cell Biol. 2003;23:7973-7981.

    Not in our library10.1128/mcb.23.22.7973-7981.2003

  252. 252.

    Sun Y, Butte NF, Garcia JM, Smith RG. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance. Endocrinology. 2008;149:843-850.

    Not in our library10.1210/en.2007-0271

  253. 253.

    Mani BK, et al. LEAP2 changes with body mass and food intake in humans and mice. J. Clin. Invest. 2019;129:3909-3923.

    Not in our library10.1172/jci125332

  254. 254.

    Zorrilla EP, et al. Vaccination against weight gain. Proc. Natl Acad. Sci. USA. 2006;103:13226-13231.

    Not in our library10.1073/pnas.0605376103

  255. 255.

    Patterson M, Bloom SR, Gardiner JV. Ghrelin and appetite control in humans — potential application in the treatment of obesity. Peptides. 2011;32:2290-2294.

    Not in our library10.1016/j.peptides.2011.07.021

  256. 256.

    Lu SC, et al. An acyl-ghrelin-specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice. Mol. Pharmacol. 2009;75:901-907.

    Not in our library10.1124/mol.108.052852

  257. 257.

    Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 2004;84:277-359.

    Not in our library10.1152/physrev.00015.2003

  258. 258.

    Xu Z, Liu J, You W, Wang Y, Shan T. Cold exposure induces nuclear translocation of CRTC3 in brown adipose tissue. J. Cell Biochem. 2019;120:9138-9146.

    Not in our library10.1002/jcb.28189

  259. 259.

    Cao W, et al. p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol. Cell Biol. 2004;24:3057-3067.

    Not in our library10.1128/mcb.24.7.3057-3067.2004

  260. 260.

    Villarroya F, Peyrou M, Giralt M. Transcriptional regulation of the uncoupling protein-1 gene. Biochimie. 2017;134:86-92.

    Not in our library10.1016/j.biochi.2016.09.017

  261. 261.

    Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. J. Med. Toxicol. 2011;7:205-212.

    Not in our library10.1007/s13181-011-0162-6

  262. 262.
  263. 263.

    Geisler JG. 2,4 Dinitrophenol as medicine. Cells. 2019;8:280.

    Not in our library10.3390/cells8030280

  264. 264.

    Perry RJ, Zhang D, Zhang XM, Boyer JL, Shulman GI. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats. Science. 2015;347:1253-1256.

    Not in our library10.1126/science.aaa0672

  265. 265.

    Axelrod CL, et al. BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol. Med. 2020;12:e12088.

    Not in our library10.15252/emmm.202012088

  266. 266.
  267. 267.

    Hale A, Veniant MM. Growth differentiation factor 15 as a potential therapeutic for treating obesity. Mol. Metab. 2021;46:101117.

    Not in our library10.1016/j.molmet.2020.101117

  268. 268.

    Assadi A, Zahabi A, Hart RA. GDF15, an update of the physiological and pathological roles it plays: a review. Pflug. Arch. 2020;472:1535-1546.

    Not in our library10.1007/s00424-020-02459-1

  269. 269.

    Kempf T, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat. Med. 2011;17:581-588.

    Not in our library10.1038/nm.2354

  270. 270.

    Mullican SE, et al. GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat. Med. 2017;23:1150-1157.

    Not in our library10.1038/nm.4392

  271. 271.

    Borner T, et al. GDF15 induces anorexia through nausea and emesis. Cell Metab. 2020;31:351-362.e5.

    Not in our library10.1016/j.cmet.2019.12.004

  272. 272.

    Borner T, et al. GDF15 induces an aversive visceral malaise state that drives anorexia and weight loss. Cell Rep. 2020;31:107543.

    Not in our library10.1016/j.celrep.2020.107543

  273. 273.

    Strelau J, et al. Progressive postnatal motoneuron loss in mice lacking GDF-15. J. Neurosci. 2009;29:13640-13648.

    Not in our library10.1523/jneurosci.1133-09.2009

  274. 274.

    Tsai VWW, Husaini Y, Sainsbury A, Brown DA, Breit SN. The MIC-1/GDF15–GFRAL pathway in energy homeostasis: implications for obesity, cachexia, and other associated diseases. Cell Metab. 2018;28:353-368.

    Not in our library10.1016/j.cmet.2018.07.018

  275. 275.

    Baek SJ, et al. Nonsteroidal anti-inflammatory drug-activated gene-1 over expression in transgenic mice suppresses intestinal neoplasia. Gastroenterology. 2006;131:1553-1560.

    Not in our library10.1053/j.gastro.2006.09.015

  276. 276.

    Bagdade JD, Bierman EL, Porte D. The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J. Clin. Invest. 1967;46:1549-1557.

    Not in our library10.1172/jci105646

  277. 277.

    Stadlbauer U, Woods SC, Langhans W, Meyer U. PYY3-36: beyond food intake. Front. Neuroendocrinol. 2015;38:1-11.

    Not in our library10.1016/j.yfrne.2014.12.003

  278. 278.

    Batterham RL, et al. Gut hormone PYY(3–36) physiologically inhibits food intake. Nature. 2002;418:650-654.

    Not in our library10.1038/nature00887

  279. 279.

    Challis BG, et al. Acute effects of PYY3–36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem. Biophys. Res. Commun. 2003;311:915-919.

    Not in our library10.1016/j.bbrc.2003.10.089

  280. 280.

    Halatchev IG, Ellacott KL, Fan W, Cone RD. Peptide YY3–36 inhibits food intake in mice through a melanocortin-4 receptor-independent mechanism. Endocrinology. 2004;145:2585-2590.

    Not in our library10.1210/en.2003-1754

  281. 281.

    Batterham RL, et al. Inhibition of food intake in obese subjects by peptide YY3–36. N. Engl. J. Med. 2003;349:941-948.

    Not in our library10.1056/nejmoa030204

  282. 282.

    Degen L, et al. Effect of peptide YY3–36 on food intake in humans. Gastroenterology. 2005;129:1430-1436.

    Not in our library10.1053/j.gastro.2005.09.001

  283. 283.

    Poulsen C, et al. Rational development of stable PYY3–36 peptide Y2 receptor agonists. Pharm. Res. 2021;8:1369-1385.

    Not in our library10.1007/s11095-021-03077-x

  284. 284.

    Pratley RE, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6:275-286.

    Not in our library10.1016/s2213-8587(18)30024-x

  285. 285.

    Carvajal A, Garcia del Pozo J, Martin de Diego I, Rueda de Castro AM, Velasco A. Efficacy of fenfluramine and dexfenfluramine in the treatment of obesity: a meta-analysis. Methods Find. Exp. Clin. Pharmacol. 2000;22:285-290.

    Not in our library10.1358/mf.2000.22.5.796647

  286. 286.

    Aronne LJ, et al. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity. 2013;21:2163-2171.

    Not in our library10.1002/oby.20584

  287. 287.

    Cohen PA, Goday A, Swann JP. The return of rainbow diet pills. Am. J. Public. Health. 2012;102:1676-1686.

    Not in our library10.2105/ajph.2012.300655

  288. 288.

    Van Gaal L, Pi-Sunyer X, Despres JP, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care. 2008;31:S229-240.

    Not in our library10.2337/dc08-s258

  289. 289.

    Sjostrom L, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet. 1998;352:167-172.

    Not in our library10.1016/s0140-6736(97)11509-4

  290. 290.

    Gadde KM, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341-1352.

    Not in our library10.1016/s0140-6736(11)60205-5

  291. 291.

    Garvey WT, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am. J. Clin. Nutr. 2012;95:297-308.

    Not in our library10.3945/ajcn.111.024927

  292. 292.

    Greenway FL, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595-605.

    Not in our library10.1016/s0140-6736(10)60888-4

  293. 293.

    Pires N, et al. Safety and pharmacokinetics of withaferin-A in advanced stage high grade osteosarcoma: a phase I trial. J. Ayurveda Integr. Med. 2020;11:68-72.

    Not in our library10.1016/j.jaim.2018.12.008

  294. 294.
  295. 295.

    Clapper JR, et al. Effects of amylin and bupropion/naltrexone on food intake and body weight are interactive in rodent models. Eur. J. Pharmacol. 2013;698:292-298.

    Not in our library10.1016/j.ejphar.2012.11.010

  296. 296.

    Ji W, et al. Effects of canagliflozin on weight loss in high-fat diet-induced obese mice. PLoS ONE. 2017;12:e0179960.

    Not in our library10.1371/journal.pone.0179960

  297. 297.

    Thomsen WJ, et al. Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J. Pharmacol. Exp. Ther. 2008;325:577-587.

    Not in our library10.1124/jpet.107.133348

  298. 298.

    Hansen HH, et al. The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant. Eur. J. Pharmacol. 2010;636:88-95.

    Not in our library10.1016/j.ejphar.2010.03.026

  299. 299.

    Simonds SE, et al. Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese male mice. Diabetes. 2019;68:683-695.

    Not in our library10.2337/db18-1149

  300. 300.

    Andermann ML, Lowell BB. Toward a wiring diagram understanding of appetite control. Neuron. 2017;95:757-778.

    Not in our library10.1016/j.neuron.2017.06.014

  301. 301.

    Lutter M, Nestler EJ. Homeostatic and hedonic signals interact in the regulation of food intake. J. Nutr. 2009;139:629-632.

    Not in our library10.3945/jn.108.097618

  302. 302.

    Skibicka KP, Hansson C, Alvarez-Crespo M, Friberg PA, Dickson SL. Ghrelin directly targets the ventral tegmental area to increase food motivation. Neuroscience. 2011;180:129-137.

    Not in our library10.1016/j.neuroscience.2011.02.016

  303. 303.

    Woods SC, Lotter EC, McKay LD, Porte D. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature. 1979;282:503-505.

    Not in our library10.1038/282503a0

  304. 304.

    Woods, S. C. & Porte, D. Jr. in Hunger: Basic Mechanisms and Clinical Implications (eds Novin, D., Bray, G. A. & Wyrwichka, W.) 273–280 (Raven, 1976).

    Not in our library

  305. 305.

    Becskei C, Grabler V, Edwards GL, Riediger T, Lutz TA. Lesion of the lateral parabrachial nucleus attenuates the anorectic effect of peripheral amylin and CCK. Brain Res. 2007;1162:76-84.

    Not in our library10.1016/j.brainres.2007.06.016

  306. 306.

    Lutz TA, et al. Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats. Peptides. 1998;19:309-317.

    Not in our library10.1016/s0196-9781(97)00292-1

  307. 307.

    Riediger T, Schmid HA, Lutz T, Simon E. Amylin potently activates AP neurons possibly via formation of the excitatory second messenger cGMP. Am. J. Physiol. Regulatory, Integr. Comp. Physiol. 2001;281:R1833-R1843.

    Not in our library10.1152/ajpregu.2001.281.6.r1833

  308. 308.

    Riediger T, Zuend D, Becskei C, Lutz TA. The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut–brain axis. Am. J. Physiol. Regulatory, Integr. Comp. Physiol. 2004;286:R114-R122.

    Not in our library10.1152/ajpregu.00333.2003

  309. 309.

    Mietlicki-Baase EG, et al. Amylin modulates the mesolimbic dopamine system to control energy balance. Neuropsychopharmacology. 2015;40:372-385.

    Not in our library10.1038/npp.2014.180

  310. 310.

    Coskun T, et al. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology. 2008;149:6018-6027.

    Not in our library10.1210/en.2008-0816

  311. 311.

    Kharitonenkov A, et al. FGF-21 as a novel metabolic regulator. J. Clin. Invest. 2005;115:1627-1635.

    Not in our library10.1172/jci23606

  312. 312.

    Sarruf DA, et al. Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes. 2010;59:1817-1824.

    Not in our library10.2337/db09-1878

  313. 313.

    Chau MD, Gao J, Yang Q, Wu Z, Gromada J. Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK–SIRT1–PGC-1α pathway. Proc. Natl Acad. Sci. USA. 2010;107:12553-12558.

    Not in our library10.1073/pnas.1006962107

  314. 314.

    Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J. Comp. physiological Psychol. 1973;84:488-495.

    Not in our library10.1037/h0034870

  315. 315.

    Kissileff HR, Pi-Sunyer FX, Thornton J, Smith GP. C-terminal octapeptide of cholecystokinin decreases food intake in man. Am. J. Clin. Nutr. 1981;34:154-160.

    Not in our library10.1093/ajcn/34.2.154

  316. 316.

    Muurahainen N, Kissileff HR, Derogatis AJ, Pi-Sunyer FX. Effects of cholecystokinin-octapeptide (CCK-8) on food intake and gastric emptying in man. Physiol. Behav. 1988;44:645-649.

    Not in our library10.1016/0031-9384(88)90330-7

  317. 317.

    Moran TH, Baldessarini AR, Salorio CF, Lowery T, Schwartz GJ. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am. J. Physiol. 1997;272:R1245-R1251.

    Not in our library10.1152/ajpregu.1997.272.4.r1245

  318. 318.

    Moran TH, Robinson PH, Goldrich MS, McHugh PR. Two brain cholecystokinin receptors: implications for behavioral actions. Brain Res. 1986;362:175-179.

    Not in our library10.1016/0006-8993(86)91413-7

  319. 319.

    Alhadeff AL, Rupprecht LE, Hayes MR. GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake. Endocrinology. 2012;153:647-658.

    Not in our library10.1210/en.2011-1443

  320. 320.

    Dickson SL, et al. The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors. J. Neurosci. 2012;32:4812-4820.

    Not in our library10.1523/jneurosci.6326-11.2012

  321. 321.

    Dossat AM, Lilly N, Kay K, Williams DL. Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake. J. Neurosci. 2011;31:14453-14457.

    Not in our library10.1523/jneurosci.3262-11.2011

  322. 322.

    Terrill SJ, et al. Role of lateral septum glucagon-like peptide 1 receptors in food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2016;311:R124-R132.

    Not in our library10.1152/ajpregu.00460.2015

  323. 323.

    Muller TD, Finan B, Clemmensen C, DiMarchi RD, Tschop MH. The new biology and pharmacology of glucagon. Physiol. Rev. 2017;97:721-766.

    Not in our library10.1152/physrev.00025.2016

  324. 324.

    Weintraub M, et al. Long-term weight control study. V (weeks 190 to 210). Follow-up of participants after cessation of medication. Clin. Pharmacol. Ther. 1992;51:615-618.

    Not in our library10.1038/clpt.1992.73

  325. 325.

    Weintraub M, et al. Long-term weight control study. IV (weeks 156 to 190). The second double-blind phase. Clin. Pharmacol. Ther. 1992;51:608-614.

    Not in our library10.1038/clpt.1992.72

  326. 326.

    Weintraub M, Sundaresan PR, Schuster B, Moscucci M, Stein EC. Long-term weight control study. III (weeks 104 to 156). An open-label study of dose adjustment of fenfluramine and phentermine. Clin. Pharmacol. Ther. 1992;51:602-607.

    Not in our library10.1038/clpt.1992.71

  327. 327.

    Cambon D, Leclercq F. Clinical and echographic characteristics of patients exposed to fenfluramin or its derivatives: results of a prospective, single-centre, observational study. Arch. Cardiovasc. Dis. 2015;108:172-180.

    Not in our library10.1016/j.acvd.2014.10.006

  328. 328.

    Kurz, X. & Van Ermen, A. Valvular heart disease associated with fenfluramine–phentermine. N. Engl. J. Med.337, 1772–1773; author reply 1775 (1997).

    Not in our library

  329. 329.

    Rasmussen, S., Corya, B. C. & Glassman, R. D. Valvular heart disease associated with fenfluramine–phentermine. N. Engl. J. Med.337, 1773; author reply 1775 (1997).

    Not in our library

  330. 330.

    Astrup A, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1906-1913.

    Not in our library10.1016/s0140-6736(08)61525-1

  331. 331.

    Maggioni AP, et al. Relation between weight loss and causes of death in patients with cardiovascular disease: finding from the SCOUT trial. J. Cardiovasc. Med. 2017;18:144-151.

    Not in our library10.2459/jcm.0000000000000492

  332. 332.

    Harrison-Woolrych M, Ashton J, Herbison P. Fatal and non-fatal cardiovascular events in a general population prescribed sibutramine in New Zealand: a prospective cohort study. Drug. Saf. 2010;33:605-613.

    Not in our library10.2165/11532440-000000000-00000

  333. 333.

    Horn, H., Bohme, B., Dietrich, L. & Koch, M. Endocannabinoids in body weight control. Pharmaceuticals11, 55 (2018).

    Not in our library10.3390/ph11020055

  334. 334.

    Taylor D. Withdrawal of rimonabant — walking the tightrope of 21st century pharmaceutical regulation? Curr. Drug. Saf. 2009;4:2-4.

    Not in our library10.2174/157488609787354396

Cited by papers we hold 8

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.