Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity

Obesity Reviews

Volumn 18, Issue 1, 2017, Pages 86-98

  Burcelin, R ^a   Gourdy, P ^a,b  

^a Departments of Clinical Biochemistry and Sports Medicine   (France)

^b TOULOUSE UNIVERSITY HOSPITAL   (France)

Author keywords

GLP 1; obesity; overweight; satiety

Indexed keywords

AMYLIN; CHOLECYSTOKININ; GHRELIN; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; LIRAGLUTIDE; PEPTIDE YY; ANTIDIABETIC AGENT; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR;

CALORIC INTAKE; COMORBIDITY; DRUG APPROVAL; FOOD INTAKE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTENSION; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHARMACEUTICAL CARE; REVIEW; SLEEP DISORDERED BREATHING; WEIGHT REDUCTION; AGONISTS; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; METABOLISM; OVERWEIGHT; RANDOMIZED CONTROLLED TRIAL (TOPIC);

APPETITE REGULATION; COMORBIDITY; DIABETES MELLITUS, TYPE 2; GLUCAGON-LIKE PEPTIDE 1; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; HUMANS; HYPOGLYCEMIC AGENTS; LIRAGLUTIDE; OBESITY; OVERWEIGHT; RANDOMIZED CONTROLLED TRIALS AS TOPIC; WEIGHT LOSS;

EID: 84987858892     PISSN: 14677881     EISSN: 1467789X     Source Type: Journal    
DOI: 10.1111/obr.12465     Document Type: Review

References (75)

1. Ng M, Fleming T, Robinson M et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 766–781.
2. Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 2009; 9: 88. DOI: 10.1186/1471-2458-9-88.
3. Keum N, Greenwood DC, Lee DH et al. Adult weight gain and adiposity-related cancers: a dose–response meta-analysis of prospective observational studies. J Natl Cancer Inst 2015; 107. pii: djv088.
4. Apovian CM. The clinical and economic consequences of obesity. Am J Manag Care 2013; 19: s219–s228.
5. Wolf AM, Colditz GA. The cost of obesity: the US perspective. Pharmacoeconomics 1994; 5: 34–37.
6. Oster G, Thompson D, Edelsberg J, Bird AP, Colditz GA. Lifetime health and economic benefits of weight loss among obese persons. Am J Publ Health 1999; 89: 1536–1542.
7. Jensen MD, Ryan DH, Apovian CM et al. AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 2014; 63: 2985–3023.
8. Kim GW, Lin JE, Blomain ES, Waldman SA. Antiobesity pharmacotherapy: new drugs and emerging targets. Clin Pharmacol Ther 2014; 95: 53–66.
9. Côté CD, Zadeh-Tahmasebi M, Rasmussen BA, Duca FA, Lam TK. Hormonal signaling in the gut. J Biol Chem 2014; 289: 11642–11649.
10. Suzuki K, Jayasena CN, Bloom SR. Obesity and appetite control. Exp Diabetes Res 2012: 824305. DOI: 10.1155/2012/824305.
11. van Bloemendaal L, Ten Kulve JS, la Fleur SE, Ijzerman RG, Diamant M. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol 2013; 221: T1–T16.
12. Skibicka KP. The central GLP-1: implications for food and drug reward. Front Neurosci 2013; 7: 181.
13. Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science 2005; 307: 1909–1914.
14. Simpson KA, Martin NM, Bloom SR. Hypothalamic regulation of appetite. Exp Rev Endocrinol Metab 2008; 3: 577–592.
15. Berna MJ, Tapia JA, Sancho V, Jensen RT. Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have therapeutic potential. Curr Opin Pharmacol 2007; 7: 583–592.
16. Troke RC, Tan TM, Bloom SR. The future role of gut hormones in the treatment of obesity. Ther Adv Chronic Dis 2014; 5: 4–14.
17. Sloth B, Davidsen L, Holst JJ, Flint A, Astrup A. Effect of subcutaneous injections of PYY1-36 and PYY3-36 on appetite, ad libitum energy intake, and plasma free fatty acid concentration in obese males. Am J Physiol Endocrinol Metab 2007; 293: E604–E609.
18. Sloth B, Holst JJ, Flint A, Gregersen NT, Astrup A. Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects. Am J Physiol Endocrinol Metab 2007; 292: E1062–E1068.
19. Greenwood HC, Bloom SR, Murphy KG. Peptides and their potential role in the treatment of diabetes and obesity. Rev Diabet Stud 2011; 8: 355–368.
20. Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, Weyer C. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care 2008; 31: 1816–1823.
21. Larsen PJ, Tang-Christensen M, Holst JJ, Orskov C. Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience 1997; 77: 257–270.
22. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999; 20: 68–100.
23. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007; 87: 1409–1439.
24. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Exenatide-113 Clinical Study Group. Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2628–2635.
25. Robinson LE, Holt TA, Rees K, Randeva HS, O'Hare JP. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open 2013; 3: e001986.
26. Nauck MM, Frid A, Hermansen K et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009; 32: 84–90.
27. Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998; 101: 515–520.
28. Plamboeck A, Veedfald S, Deacon CF et al. Characterisation of oral and i.v. glucose handling in truncally vagotomised subjects with pyloroplasty. Eur J Endocrinol 2013; 169: 187–201.
29. Verdich C, Toubro S, Buemann B, Lysgård Madsen J, Holst JJ, Astrup A. The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction. Int J Obes Relat Metab Disord 2001; 25: 1206–1214.
30. Vilsbøll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept 2003; 114: 115–121.
31. Ahrén B, Holst JJ. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 2001; 50: 1030–1038.
32. Shirazi-Beechey SP, Daly K, Al-Rammahi M, Moran AW, Bravo D. Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing. Br J Nutr 2014; 111: S8–S15.
33. Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001; 50: 609–613.
34. Navarro M, Rodriquez de Fonseca F, Alvarez E et al. Colocalization of glucagon-like peptide-1 (GLP-1) receptors, glucose transporter GLUT-2, and glucokinase mRNAs in rat hypothalamic cells: evidence for a role of GLP-1 receptor agonists as an inhibitory signal for food and water intake. J Neurochem 1996; 67: 1982–1991.
35. Gutzwiller JP, Drewe J, Göke B et al. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol 1999; 276: R1541–R1544.
36. Naslund E, Barkeling B, King N et al. Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 1999; 23: 304–311.
37. Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 1995; 136: 3585–3596.
38. Belza A, Ritz C, Sørensen MQ, Holst JJ, Rehfeld JF, Astrup A. Contribution of gastroenteropancreatic appetite hormones to protein-induced satiety. Am J Clin Nutr 2013; 97: 980–989.
39. Cabou C, Burcelin R. GLP-1, the gut–brain, and brain–periphery axes. Rev Diabet Stud 2011; 8: 418–431.
40. Janssen P, Vanden Berghe P, Verschueren S, Lehmann A, Depoortere I, Tack J. Review article: the role of gastric motility in the control of food intake. Aliment Pharmacol Ther 2011; 33: 880–894.
41. Burcelin R, Gourdy P, Dalle S. GLP-1-based strategies: a physiological analysis of differential mode of action. Physiology (Bethesda) 2014; 29: 108–121.
42. Drucker DJ. Deciphering metabolic messages from the gut drives therapeutic innovation: the 2014 Banting Lecture. Diabetes 2015; 64: 317–326.
43. van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WH. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond) 2014; 38: 784–793.
44. Lean M, Le Roux C, Fujioka K et al. The impact of gastrointestinal adverse events on weight loss with liraglutide 3.0 mg as adjunct to a diet and exercise program. Endocr Pract 2015; 21: 118–119 (Abstract 611).
45. Dickson SL, Shirazi RH, Hansson C, Bergquist F, Nissbrandt H, Skibicka KP. 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.
46. Pannacciulli N, Le DS, Salbe AD et al. Postprandial glucagon-like peptide-1 (GLP-1) response is positively associated with changes in neuronal activity of brain areas implicated in satiety and food intake regulation in humans. Neuroimage 2007; 35: 511–517.
47. Secher A, Jelsing J, Baquero AF et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest 2014; 124: 4473–4488.
48. Sisley S, Gutierrez-Aguilar R, Scott M, D'Alessio DA, Sandoval DA, Seeley RJ. Neuronal GLP1R mediates liraglutide's anorectic but not glucose-lowering effect. J Clin Invest 2014; 124: 2456–2463.
49. Astrup A, Carraro R, Finer N et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond) 2012; 36: 843–854.
50. Pi-Sunyer X, Astrup A, Fujioka K et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 2015; 373: 11–22.
51. Davies MJ, Bergenstal R, Bode B et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA 2015; 314: 687–699.
52. Wadden TA, Hollander P, Klein S et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the Scale Maintenance randomized study. Int J Obes (Lond) 2013; 37: 1443–1451.
53. Dushay J, Gao C, Gopalakrishnan GS et al. Short-term exenatide treatment leads to significant weight loss in a subset of obese women without diabetes. Diabetes Care 2012; 35: 4–11.
54. Kelly AS, Metzig AM, Rudser KD et al. Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study. Obesity (Silver Spring) 2012; 20: 364–370.
55. Drucker DJ, Buse JB, Taylor K et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008; 372: 1240–1250.
56. Blevins T, Pullman J, Malloy J et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab 2011; 96: 1301–1310.
57. Buse JB, Nauck M, Forst T et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet 2013; 381: 117–124.
58. Rosenstock J, Klaff LJ, Schwartz S et al. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care 2010; 33: 1173–1175.
59. Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93: 2670–2678.
60. Rosenstock J, Reusch J, Bush M, Yang F, Stewart M, Albiglutide Study Group. Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing. Diabetes Care 2009; 32: 1880–1886.
61. Pratley RE, Nauck MA, Barnett AH et al. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol 2014; 2: 289–297.
62. Wysham C, Blevins T, Arakaki R et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care 2014; 37: 2159–2167.
63. Skrivanek Z, Gaydos BL, Chien JY et al. Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5). Diabetes Obes Metab 2014; 16: 748–756.
64. Dungan KM, Povedano ST, Forst T et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet 2014; 384: 1349–1357.
65. Buse JB, Rosenstock J, Sesti G et al. LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; 374: 39–47.
66. Rosenstock J, Raccah D, Korányi L et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care 2013; 36: 2945–2951.
67. Bolli GB, Munteanu M, Dotsenko S et al. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med 2014; 31: 176–184.
68. Hollander P, Lasko B, Barnett AH et al. Effects of taspoglutide on glycemic control and body weight in obese patients with type 2 diabetes (T-emerge 7 study). Obesity (Silver Spring) 2013; 21: 238–247.
69. Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R. Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study. Diabetes Care 2009; 32: 1237–1243.
70. Blackman A, Foster G, Zammit G et al. Liraglutide 3.0 mg reduces severity of obstructive sleep apnoea and body weight in obese individuals with moderate or severe disease: SCALE sleep apnoea trial. Diabetologia 2014; 57: S85.
71. FDA Briefing Document. NDA 206321. 2014. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed 30 March 2016.
72. Saxenda® (Liraglutide 6 mg/ml). Summary of Product Characteristics. Novo Nordisk A/S: Bagsværd, Denmark, 2015.
73. Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016. DOI: 10.1056/NEJMoa1603827.
74. Pinelli NR, Jantz A, Smith Z et al. Effect of administration time of exenatide on satiety responses, blood glucose, and adverse events in healthy volunteers. J Clin Pharmacol 2011; 51: 165–172.
75. Food and Drug Administration. Guidance for industry developing products for weight management. 2007. Available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071612.pdf. Accessed 25 May 2016.