Progress and challenges in anti-obesity pharmacotherapy

The Lancet Diabetes and Endocrinology

Volumn 6, Issue 3, 2018, Pages 237-248

  Bessesen, Daniel H ^a   Van Gaal, Luc F ^b  

^a UNIVERSITY OF COLORADO   (United States)

^b ANTWERP UNIVERSITY HOSPITAL   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ALBIGLUTIDE; AMFEBUTAMONE; AMFEBUTAMONE PLUS NALTREXONE; ANTIOBESITY AGENT; BELORANIB; CANAGLIFLOZIN; CETILISTAT; DAPAGLIFLOZIN; DEXFENFLURAMINE; DULAGLUTIDE; EXENDIN 4; FENFLURAMINE; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; HYPERGLYCEMIC AGENT; LIRAGLUTIDE; LIXISENATIDE; LORCASERIN; LY 2405319; PHENTERMINE; PHENTERMINE PLUS TOPIRAMATE; PLACEBO; RIMONABANT; ROFLUMILAST; SEMAGLUTIDE; SETMELANOTIDE; SIBUTRAMINE; TETRAHYDROLIPSTATIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZONISAMIDE;

ABNORMAL FECES; AUSTRALIA; BODY WEIGHT LOSS; CONSTIPATION; DEFECATION URGENCY; DIABETES MELLITUS; DIARRHEA; DIZZINESS; DRUG COST; DRUG EFFICACY; DRUG INDUSTRY; DRUG RESEARCH; DRUG SAFETY; DYSGEUSIA; EUROPEAN UNION; FOOD AND DRUG ADMINISTRATION; GALLBLADDER DISEASE; HEADACHE; HEALTH INSURANCE; HUMAN; HYPERTENSION; INSOMNIA; INSURANCE; JAPAN; LIFESTYLE; LIFESTYLE MODIFICATION; NAUSEA; NEUROLOGIC DISEASE; NONHUMAN; OBESITY; PANCREATITIS; PARESTHESIA; PERCEPTION; PHYSICIAN; PRESCRIPTION; PRIORITY JOURNAL; REVIEW; RISK BENEFIT ANALYSIS; SPOTTING; SUICIDAL IDEATION; SUICIDE; TACHYCARDIA; TREATMENT DURATION; UNITED STATES; VALVULAR HEART DISEASE; VITAMIN DEFICIENCY; VOMITING; XEROSTOMIA; DISEASE MANAGEMENT; DRUG EFFECT; PROGNOSIS;

ANTI-OBESITY AGENTS; DISEASE MANAGEMENT; HUMANS; OBESITY; PROGNOSIS; WEIGHT LOSS;

EID: 85029531762     PISSN: 22138587     EISSN: 22138595     Source Type: Journal    
DOI: 10.1016/S2213-8587(17)30236-X     Document Type: Review

References (116)

1. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387 (2016), 1377–1396.
2. Bray, GA, Kim, KK, Wilding, JPH, Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev 18 (2017), 715–723.
3. Van Gaal, LF, Mertens, IL, De Block, CE, Mechanisms linking obesity with cardiovascular disease. Nature 444 (2006), 875–880.
4. Apovian, CM, The clinical and economic consequences of obesity. Am J Manag Care 19:11 suppl (2013), s219–s228.
5. MacLean, PS, Wing, RR, Davidson, T, et al. NIH working group report: innovative research to improve maintenance of weight loss. Obesity (Silver Spring) 23 (2015), 7–15.
6. Galgani, J, Ravussin, E, Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond) 32:suppl 7 (2008), S109–S119.
7. Polidori, D, Sanghvi, A, Seeley, RJ, Hall, KD, How strongly does appetite counter weight loss? Quantification of the feedback control of human energy intake. Obesity (Silver Spring) 24 (2016), 2289–2295.
8. Sumithran, P, Prendergast, LA, Delbridge, E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 365 (2011), 1597–1604.
9. Fothergill, E, Guo, J, Howard, L, et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring) 24 (2016), 1612–1619.
10. Rosenbaum, M, Hirsch, J, Gallagher, DA, Leibel, RL, Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr 88 (2008), 906–912.
11. Bessesen, DH, Regulation of body weight: what is the regulated parameter?. Physiol Behav 104 (2011), 599–607.
12. Apovian, CM, Aronne, LJ, Bessesen, DH, et al. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 100 (2015), 342–362.
13. Jensen, MD, Ryan, DH, Apovian, CM, et al. 2013 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 63 (2014), 2985–3023.
14. Stegenga, H, Haines, A, Jones, K, Wilding, J, Identification, assessment, and management of overweight and obesity: summary of updated NICE guidance. BMJ, 349, 2014, g6608.
15. Thomas, CE, Mauer, EA, Shukla, AP, Rathi, S, Aronne, LJ, Low adoption of weight loss medications: a comparison of prescribing patterns of antiobesity pharmacotherapies and SGLT2s. Obesity (Silver Spring) 24 (2016), 1955–1961.
16. Zhang, S, Manne, S, Lin, J, Yang, J, Characteristics of patients potentially eligible for pharmacotherapy for weight loss in primary care practice in the United States. Obes Sci Pract 2 (2016), 104–114.
17. Del Re, AC, Frayne, SM, Harris, AH, Antiobesity medication use across the veterans health administration: patient-level predictors of receipt. Obesity (Silver Spring) 22 (2014), 1968–1972.
18. Heymsfield, SB, Wadden, TA, Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376 (2017), 254–266.
19. Wadden, TA, Berkowitz, RI, Womble, LG, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 353 (2005), 2111–2120.
20. Fujioka, K, Plodkowski, R, O'Neil, PM, Gilder, K, Walsh, B, Greenway, FL, The relationship between early weight loss and weight loss at 1 year with naltrexone ER/bupropion ER combination therapy. Int J Obes (Lond) 40 (2016), 1369–1375.
21. Mead, E, Atkinson, G, Richter, B, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev, 11, 2016 CD012436.
22. Chanoine, JP, Hampl, S, Jensen, C, Boldrin, M, Hauptman, J, Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 293 (2005), 2873–2883.
23. Apovian, CM, Aronne, L, Rubino, D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 21 (2013), 935–943.
24. 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) 36 (2012), 843–854.
25. 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 314 (2015), 687–699.
26. Magkos, F, Nikonova, E, Fain, R, Zhou, S, Ma, T, Shanahan, W, Effect of lorcaserin on glycemic parameters in patients with type 2 diabetes mellitus. Obesity (Silver Spring) 25 (2017), 842–849.
27. Marso, SP, Daniels, GH, Brown-Frandsen, K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375 (2016), 311–322.
28. Cohen, A, De Felice, EA, Leb, SM, Fuentes, JG, Rothwell, KG, Truant, AP, Double-blind comparison of efficacy, safety, and side effects of bionamin, phentermine compound, and placebo in the treatment of exogenous obesity. Curr Ther Res Clin Exp 10 (1968), 323–334.
29. Truant, AP, Olon, LP, Cobb, S, Phentermine resin as an adjunct in medical weight reduction: a controlled, randomized, double-blind prospective study. Curr Ther Res Clin Exp 14 (1972), 726–738.
30. Bray, GA, Medical treatment of obesity: the past, the present and the future. Best Pract Res Clin Gastroenterol 28 (2014), 665–684.
31. 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 12 (2010), 876–882.
32. Hollander, PA, Elbein, SC, Hirsch, IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care 21 (1998), 1288–1294.
33. Sjöström, L, Rissanen, A, Andersen, T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet 352 (1998), 167–172.
34. Davidson, MH, Hauptman, J, DiGirolamo, M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA 281 (1999), 235–242.
35. Finer, N, James, WP, Kopelman, PG, Lean, ME, Williams, G, One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord 24 (2000), 306–313.
36. Rössner, S, Sjöström, L, Noack, R, Meinders, AE, Noseda, G, Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res 8 (2000), 49–61.
37. Kelley, DE, Bray, GA, Pi-Sunyer, FX, et al. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care 25 (2002), 1033–1041.
38. Krempf, M, Louvet, JP, Allanic, H, Miloradovich, T, Joubert, JM, Attali, JR, Weight reduction and long-term maintenance after 18 months treatment with orlistat for obesity. Int J Obes Relat Metab Disord 27 (2003), 591–597.
39. Torgerson, JS, Hauptman, J, Boldrin, MN, Sjöström, L, XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 27 (2004), 155–161.
40. Gadde, KM, Allison, DB, Ryan, DH, 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 377 (2011), 1341–1352.
41. Allison, DB, Gadde, KM, Garvey, WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 20 (2012), 330–342.
42. Smith, SR, Weissman, NJ, Anderson, CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 363 (2010), 245–256.
43. Fidler, MC, Sanchez, M, Raether, B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 96 (2011), 3067–3077.
44. O'Neil, PM, Smith, SR, Weissman, NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring) 20 (2012), 1426–1436.
45. Greenway, FL, Fujioka, K, Plodkowski, RA, 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 376 (2010), 595–605.
46. Wadden, TA, Foreyt, JP, Foster, GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 19 (2011), 110–120.
47. Hollander, P, Gupta, AK, Plodkowski, R, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care 36 (2013), 4022–4029.
48. 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) 37 (2013), 1443–1451.
49. 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 373 (2015), 11–22.
50. le Roux, CW, Astrup, A, Fujioka, K, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet 389 (2017), 1399–1409.
51. Van Gaal, L, Dirinck, E, Pharmacological approaches in the treatment and maintenance of weight loss. Diabetes Care 39:suppl 2 (2016), S260–S267.
52. Weintraub, M, Sundaresan, PR, Schuster, B, et al. Long-term weight control study. II (weeks 34 to 104). An open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise. Clin Pharmacol Ther 51 (1992), 595–601.
53. Kopelman, P, Groot Gde, H, Rissanen, A, et al. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (xenical). Obesity (Silver Spring) 18 (2010), 108–115.
54. Khera, R, Murad, MH, Chandar, AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA 315 (2016), 2424–2434.
55. Yanovski, SZ, Yanovski, JA, Long-term drug treatment for obesity: a systematic and clinical review. JAMA 311 (2014), 74–86.
56. Smith, SR, Garvey, WT, Greenway, FL, et al. Coadministration of lorcaserin and phentermine for weight management: a 12-week, randomized, pilot safety study. Obesity (Silver Spring) 25 (2017), 857–865.
57. Nissen, SE, Wolski, KE, Prcela, L, 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 315 (2016), 990–1004.
58. Burcelin, R, Gourdy, P, Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity. Obes Rev 18 (2017), 86–98.
59. Astrup, A, Rössner, S, Van Gaal, L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 374 (2009), 1606–1616.
60. Armstrong, MJ, Gaunt, P, Aithal, GP, et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 387 (2016), 679–690.
61. Bjerre Knudsen, L, Madsen, LW, Andersen, S, et al. Glucagon-like peptide-1 receptor agonists activate rodent thyroid c-cells causing calcitonin release and c-cell proliferation. Endocrinology 151 (2010), 1473–1486.
62. Kumar, RB, Aronne, LJ, Efficacy comparison of medications approved for chronic weight management. Obesity (Silver Spring) 23:suppl 1 (2015), S4–S7.
63. Hampp, C, Kang, EM, Borders-Hemphill, V, Use of prescription antiobesity drugs in the United States. Pharmacotherapy 33 (2013), 1299–1307.
64. Block, JP, Choudhry, NK, Carpenter, DP, et al. Time series analyses of the effect of FDA communications on use of prescription weight loss medications. Obesity (Silver Spring) 22 (2014), 943–949.
65. James, WPT, Caterson, ID, Coutinho, W, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 363 (2010), 905–917.
66. Tyczynski, JE, Oleske, DM, Klingman, D, Ferrufino, CP, Lee, WC, Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study. Drug Saf 35 (2012), 629–644.
67. 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 (Lond) 39 (2015), 1359–1364.
68. Van Gaal, LF, Rissanen, AM, Scheen, AJ, Ziegler, O, Rössner, S, 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 365 (2005), 1389–1397.
69. Christensen, R, Kristensen, PK, Bartels, EM, Bliddal, H, Astrup, A, Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 370 (2007), 1706–1713.
70. Magkos, F, Fraterrigo, G, Yoshino, J, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab 23 (2016), 591–601.
71. Foster, GD, Wadden, TA, Vogt, RA, Brewer, G, What is a reasonable weight loss? Patients' expectations and evaluations of obesity treatment outcomes. J Consult Clin Psychol 65 (1997), 79–85.
72. Andrews, M, Many insurers do not cover drugs approved to help people lose weight. Kaiser Health News. http://khn.org/news/many-insurers-do-not-cover-drugs-approved-to-help-people-lose-weight/, Jan 6, 2015 (accessed Aug 29, 2017).
73. Wilson, ER, Kyle, TK, Nadglowski, JF Jr, Stanford, FC, Obesity coverage gap: consumers perceive low coverage for obesity treatments even when workplace wellness programs target BMI. Obesity (Silver Spring) 25 (2017), 370–377.
74. Baum, C, Andino, K, Wittbrodt, E, Stewart, S, Szymanski, K, Turpin, R, The challenges and opportunities associated with reimbursement for obesity pharmacotherapy in the USA. Pharmacoeconomics 33 (2015), 643–653.
75. Smith, AW, Borowski, LA, Liu, B, et al. U.S. primary care physicians' diet-, physical activity-, and weight-related care of adult patients. Am J Prev Med 41 (2011), 33–42.
76. Petrin, C, Kahan, S, Turner, M, Gallagher, C, Dietz, WH, Current practices of obesity pharmacotherapy, bariatric surgery referral and coding for counselling by healthcare professionals. Obes Sci Pract 2 (2016), 266–271.
77. Yeh, JS, Kushner, RF, Schiff, GD, Obesity and management of weight loss. N Engl J Med 375 (2016), 1187–1189.
78. Phelan, SM, Burgess, DJ, Yeazel, MW, Hellerstedt, WL, Griffin, JM, van Ryn, M, Impact of weight bias and stigma on quality of care and outcomes for patients with obesity. Obes Rev 16 (2015), 319–326.
79. Hebl, MR, Xu, J, Weighing the care: physicians' reactions to the size of a patient. Int J Obes Relat Metab Disord 25 (2001), 1246–1252.
80. Puhl, RM, Heuer, CA, The stigma of obesity: a review and update. Obesity (Silver Spring) 17 (2009), 941–964.
81. Colon-Gonzalez, F, Kim, GW, Lin, JE, Valentino, MA, Waldman, SA, Obesity pharmacotherapy: what is next?. Mol Aspects Med 34 (2013), 71–83.
82. Gadde, KM, Yonish, GM, Foust, MS, Wagner, HR, Combination therapy of zonisamide and bupropion for weight reduction in obese women: a preliminary, randomized, open-label study. J Clin Psychiatry 68 (2007), 1226–1229.
83. Kim, DD, Krishnarajah, J, Lillioja, S, et al. Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial. Diabetes Obes Metab 17 (2015), 566–572.
84. Kühnen, P, Clément, K, Wiegand, S, et al. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med 375 (2016), 240–246.
85. Gaich, G, Chien, JY, Fu, H, et al. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 18 (2013), 333–340.
86. Jensterle, M, Kocjan, T, Janez, A, Phosphodiesterase 4 inhibition as a potential new therapeutic target in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 99 (2014), e1476–e1481.
87. Tschöp, MH, Finan, B, Clemmensen, C, et al. Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metab 24 (2016), 51–62.
88. Hukshorn, CJ, Saris, WH, Westerterp-Plantenga, MS, Farid, AR, Smith, FJ, Campfield, LA, Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. J Clin Endocrinol Metab 85 (2000), 4003–4009.
89. Moon, HS, Matarese, G, Brennan, AM, et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes 60 (2011), 1647–1656.
90. Liu, J, Lee, J, Salazar Hernandez, MA, Mazitschek, R, Ozcan, U, Treatment of obesity with celastrol. Cell 161 (2015), 999–1011.
91. Lee, J, Liu, J, Feng, X, et al. Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice. Nat Med 22 (2016), 1023–1032.
92. Heymsfield, SB, Greenberg, AS, Fujioka, K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282 (1999), 1568–1575.
93. Kim, GW, Lin, JE, Blomain, ES, Waldman, SA, Antiobesity pharmacotherapy: new drugs and emerging targets. Clin Pharmacol Ther 95 (2014), 53–66.
94. Anderson, JW, Greenway, FL, Fujioka, K, Gadde, KM, McKenney, J, O'Neil, PM, Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res 10 (2002), 633–641.
95. Gadde, KM, Parker, CB, Maner, LG, et al. Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women. Obes Res 9 (2001), 544–551.
96. Gadde, KM, Kopping, MF, Wagner, HR 2nd, Yonish, GM, Allison, DB, Bray, GA, Zonisamide for weight reduction in obese adults: a 1-year randomized controlled trial. Arch Intern Med 172 (2012), 1557–1564.
97. Moran, TH, Dailey, MJ, Gut peptides: targets for antiobesity drug development?. Endocrinology 150 (2009), 2526–2530.
98. Andrade, S, Pinho, F, Ribeiro, AM, et al. Immunization against active ghrelin using virus-like particles for obesity treatment. Curr Pharm Des 19 (2013), 6551–6558.
99. Teuffel, P, Wang, L, Prinz, P, et al. Treatment with the ghrelin-O-acyltransferase (GOAT) inhibitor GO-CoA-Tat reduces food intake by reducing meal frequency in rats. J Physiol Pharmacol 66 (2015), 493–503.
100. Giralt, M, Gavaldà-Navarro, A, Villarroya, F, Fibroblast growth factor-21, energy balance and obesity. Mol Cell Endocrinol 418 (2015), 66–73.
101. Rhythm pharmaceuticals. Product pipeline. Peptide therapeutics for rare genetic deficiencies resulting in life-threatening metabolic disorders. http://www.rhythmtx.com/pipeline/product-pipeline/ (accessed Aug 8, 2017).
102. Vilsbøll, T, Christensen, M, Junker, AE, Knop, FK, Gluud, LL, Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ, 344, 2012, d7771.
103. 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 33 (2010), 1173–1175.
104. Marso, SP, Bain, SC, Consoli, A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 375 (2016), 1834–1844.
105. Bays, HE, Weinstein, R, Law, G, Canovatchel, W, Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring) 22 (2014), 1042–1049.
106. Devenny, JJ, Godonis, HE, Harvey, SJ, Rooney, S, Cullen, MJ, Pelleymounter, MA, Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesity (Silver Spring) 20 (2012), 1645–1652.
107. Ferrannini, G, Hach, T, Crowe, S, Sanghvi, A, Hall, KD, Ferrannini, E, Energy balance after sodium-glucose cotransporter 2 inhibition. Diabetes Care 38 (2015), 1730–1735.
108. Frías, JP, Guja, C, Hardy, E, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol 4 (2016), 1004–1016.
109. Lundkvist, P, Sjöström, CD, Amini, S, Pereira, MJ, Johnsson, E, Eriksson, JW, Dapagliflozin once-daily and exenatide once-weekly dual therapy: a 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes. Diabetes Obes Metab 19 (2017), 49–60.
110. Field, BC, Wren, AM, Peters, V, et al. PYY3–36 and oxyntomodulin can be additive in their effect on food intake in overweight and obese humans. Diabetes 59 (2010), 1635–1639.
111. Hollander, P, Bays, HE, Rosenstock, J, et al. Coadministration of canagliflozin and phentermine for weight management in overweight and obese individuals without diabetes: a randomized clinical trial. Diabetes Care 40 (2017), 632–639.
112. Clemmensen, C, Finan, B, Fischer, K, et al. Dual melanocortin-4 receptor and GLP-1 receptor agonism amplifies metabolic benefits in diet-induced obese mice. EMBO Mol Med 7 (2015), 288–298.
113. De Silva, A, Salem, V, Long, CJ, et al. The gut hormones PYY 3–36 and GLP-1 7–36 amide reduce food intake and modulate brain activity in appetite centers in humans. Cell Metab 14 (2011), 700–706.
114. Finan, B, Yang, B, Ottaway, N, et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med 21 (2015), 27–36.
115. Vogel, H, Wolf, S, Rabasa, C, et al. GLP-1 and estrogen conjugate acts in the supramammillary nucleus to reduce food-reward and body weight. Neuropharmacology 110 (2016), 396–406.
116. Finan, B, Clemmensen, C, Zhu, Z, et al. Chemical hybridization of glucagon and thyroid hormone optimizes therapeutic impact for metabolic disease. Cell, 167, 2016, 843 57.e14.