Skip to main content
Top

04-19-2017 | Obesity | Review | Article

Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

Journal: Acta Diabetologica

Authors: Carl A. Roberts, Paul Christiansen, Jason C. G. Halford

Publisher: Springer Milan

Abstract

Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity. Yet, with regard to pharmacotherapy for obesity, we are far from true personalised medicine. We review the limited mechanistic data with four mono and combination pharmacotherapies, to assess the potential for tailoring their use to target specific obesogenic behaviours. Potential treatment options are considered, but in the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options.
Literature
1.
Zhang Z, Wang M (2012) Obesity, a health burden of a global nature. Acta Pharmacol Sin 33(2):145–147CrossRefPubMedPubMedCentral
2.
Public Health England. Making the case for tackling obesity—why invest? February 2015. http://​bit.​ly/​1EA6iXF
3.
Blundell JE, King NA (1996). Overconsumption as a cause of weight gain: behavioural–physiological interactions in the control of food intake (appetite). Ciba foundation symposium 201—the origins and consequences of obesity, Wiley Online Library
4.
Blundell JE, Cooling J (2000) Routes to obesity: phenotypes, food choices and activity. Br J Nutr 83(1):33–38
5.
Blundell JE, Stubs RJ, Golding C et al (2005) Resistance and susceptibility to weight gain: individual variability in response to a high-fat diet. Physiol Behav 86(5):614–622CrossRefPubMed
6.
Nijs IM, Muris P, Euser AS, Franken IHA (2010) Differences in attention to food and food intake between overweight/obese and normal-weight females under conditions of hunger and satiety. Appetite 54(2):243–254CrossRefPubMed
7.
Massey A, Hill AJ (2012) Dieting and food craving. A descriptive, quasi-prospective study. Appetite 58(3):781–785CrossRefPubMed
8.
Warren C, Cooper PJ (1988) Psychological effects of dieting. Br J Clin Psychol 27(3):269–270CrossRefPubMed
9.
Keys A, Brožek J, Henschel A, Mickelsen O, Taylor HL (1950). The biology of human starvation.(2 vols)
10.
Jasinska AJ, Yasuda M, Burant CF et al (2012) Impulsivity and inhibitory control deficits are associated with unhealthy eating in young adults. Appetite 59(3):738–747CrossRefPubMedPubMedCentral
11.
Locke AE, Kahali B, Berndt SI et al (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature 518(7538):197–206CrossRefPubMedPubMedCentral
12.
Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826):889–894CrossRefPubMedPubMedCentral
13.
Wardle J, Carnell S, Haworth CMA, Farooqi IS, O’Rahilly S, Plomin R (2008) Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 93(9):3640–3643CrossRefPubMed
14.
Llewellyn CH, Trzaskowski M, van Jaarsveld CHM, Plomin R, Wardle J (2014) Satiety mechanisms in genetic risk of obesity. JAMA pediatr 168(4):338–344CrossRefPubMedPubMedCentral
15.
Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CNA (2008) An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 359(24):2558–2566CrossRefPubMed
16.
Wardle J, Llewellyn CH, Sanderson S, Plomin R (2009) The FTO gene and measured food intake in children. Int J Obes 33(1):42–45CrossRef
17.
Tanofsky-Kraff M, Han JC, Anandalingam K et al (2009) The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am J Clin Nutr 90(6):1483–1488CrossRefPubMedPubMedCentral
18.
van Jaarsveld CH, Boniface D, Llewellyn CH, Wardle J (2014) Appetite and growth: a longitudinal sibling analysis. JAMA pediatr 168(4):345–350CrossRefPubMed
19.
Syrad, H, Llewellyn CH, Johnson L et al. (2016) Meal size is a critical driver of weight gain in early childhood. Scientific Reports 6
20.
Welbourn R, Dixon J, Barth JH et al (2016) NICE-accredited commissioning guidance for weight assessment and management clinics: a model for a specialist multidisciplinary team approach for people with severe obesity. Obes Surg 26(3):649–659CrossRefPubMed
21.
Cabou C, Burcelin R (2011) GLP-1, the gut-brain, and brain-periphery axes. Rev Diabet Stud 8(3):418–431CrossRefPubMedPubMedCentral
22.
Katsurada K, Yada T (2016) Neural effects of gut-and brain-derived glucagon-like peptide-1 and its receptor agonist. J Diabetes Investig 7(S1):64–69CrossRefPubMedPubMedCentral
23.
Krieger JP, Arnold M, Pettersen KG, Lossel P, Langhans W, Lee SJ (2016) Knockdown of GLP-1 receptors in vagal afferents affects normal food intake and glycemia. Diabetes 65(1):34–43PubMed
24.
Kanoski SE, Rupprecht LE, Fortin SM, De Jonghe BC, Hayes MR (2012) The role of nausea in food intake and body weight suppression by peripheral GLP-1 receptor agonists, exendin-4 and liraglutide. Neuropharmacology 62(5):1916–1927CrossRefPubMed
25.
Secher A, Jelsing J, Baquero AF et al (2014) The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Investig 124(10):4473–4488CrossRefPubMedPubMedCentral
26.
Alhadeff AL, Rupprecht LE, Hayes MR (2011) 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 153(2):647–658CrossRefPubMedPubMedCentral
27.
Khera R, Murad MH, Chandar AK et al (2016) Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA 315(22):2424–2434CrossRefPubMed
28.
Inoue K, Maeda N, Kashine S et al (2011) Short-term effects of liraglutide on visceral fat adiposity, appetite, and food preference: a pilot study of obese Japanese patients with type 2 diabetes. Cardiovasc Diabetol 1(10):109. doi:10.​1186/​1475-2840-10-109 CrossRef
29.
Horowitz M, Flint A, Jones KL et al (2012) Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes. Diabetes Res Clin Pract 97(2):258–266CrossRefPubMed
30.
Flint A, Kapitza C, Zdravkovic M (2013) The once-daily human GLP-1 analogue liraglutide impacts appetite and energy intake in patients with type 2 diabetes after short-term treatment. Diabetes Obes Metab 15(10):958–962CrossRefPubMed
31.
van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WHM (2014) 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 38(6):784–793CrossRef
32.
Farr OM, Sofopoulos M, Tsoukas MA et al (2016) GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia 59(5):954–965CrossRefPubMedPubMedCentral
33.
Button KS, Ioannidis JPA, Mokrysz C et al (2013) Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci 14(5):365–376CrossRefPubMed
34.
Goldstein MG (1998) Bupropion sustained release and smoking cessation. J Clin Psychiatr 59(4):66–72
35.
Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O’neil PM (2002) Bupropion SR enhances weight loss: a 48-week double-blind placebo-controlled trial. Obes Res 10(7):633–641CrossRefPubMed
36.
Caixas A, Albert L, Capel I, Rigla M (2014) Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date. Drug Des Dev Ther 8:1419CrossRef
37.
Lee MW, Fujioka K (2009) Naltrexone for the treatment of obesity: review and update. Expert Opin Pharmacother 10(11):1841–1845CrossRefPubMed
38.
Greenway FL, Whitehouse MJ, Guttadauria M et al (2009) Rational design of a combination medication for the treatment of obesity. Obesity 17(1):30–39CrossRefPubMed
39.
Greenway FL, Fujioka K, Plodkowski RA et al (2010) 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(9741):595–605CrossRefPubMed
40.
Apovian CM, Aronne L, Rubino D et al (2013) A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity 21(5):935–943CrossRefPubMedPubMedCentral
41.
Wadden TA, Foreyt JP, Foster JD et al (2011) Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity 19(1):110–120CrossRefPubMed
42.
Wang GJ, Tomasi D, Volkow MD et al (2014) Effect of combined naltrexone and bupropion therapy on the brain’s reactivity to food cues. Int J Obes 38(5):682–688CrossRef
43.
Halford JCG, Boyland EJ, Blundell JE, Kirkham TC, Harrold JA (2010) Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol 6(5):255–269CrossRefPubMed
44.
Heisler LK, Jobst EE, Sutton GM et al (2006) Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51(2):239–249CrossRefPubMed
45.
Smith S, Weissman NJ, Anderson CM et al (2010) Behavioral modification and lorcaserin for overweight and obesity management (bloom) study group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 363(3):245–256CrossRefPubMed
46.
O’neil PM, Smith SR, Weissman NJ et al (2012) Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity 20(7):1426–1436CrossRefPubMed
47.
Fidler MC, Sanchez M, Raether B et al (2011) A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 96(10):3067–3077CrossRefPubMed
48.
Martin CK, Redman LM, Zhang J et al (2010) Lorcaserin, a 5-HT2C receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J Clin Endocrinol Metab 96(3):837–845CrossRefPubMedPubMedCentral
49.
Farr OM, Upadhyay J, Gavrieli R et al (2016) Lorcaserin administration decreases activation of brain centers in response to food cues and these emotion-and salience-related changes correlate with weight loss effects: a four week long randomized, placebo-controlled, double-blinded clinical trial. Diabetes 65(10):2943–2953CrossRefPubMed
50.
Allison DB, Gadde KM, Garvey WT et al (2012) Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity 20(2):330–342CrossRefPubMed
51.
Rothman RB, Baumann MH, Dersch CM et al (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39(1):32–41CrossRefPubMed
52.
Li Z, Maglione M, Tu W et al (2005) Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 142(7):532–546CrossRefPubMed
53.
Hendricks EJ, Greenway FL, Westman EC, Gupta AK (2011) Blood pressure and heart rate effects, weight loss and maintenance during long-term phentermine pharmacotherapy for obesity. Obesity 19(12):2351–2360CrossRefPubMed
54.
Bray GA, Hollander P, Klein S et al (2003) A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 11(6):722–733CrossRefPubMed
55.
Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M (2004) A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes 28(11):1399–1410CrossRef
56.
Gadde KM, Allison DB, Ryan DH et al (2011) 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(9774):1341–1352CrossRefPubMed
57.
Li QS, Lenhard JM, Zhan Y et al (2016) A candidate-gene association study of topiramate-induced weight loss in obese patients with and without type 2 diabetes mellitus. Pharmacogenet Genom 26(2):53–65CrossRef
58.
Hauner H, Meier M, Jöckel K-H, Frey UH, Siffert W (2003) Prediction of successful weight reduction under sibutramine therapy through genotyping of the G-protein β3 subunit gene (GNB3) C825T polymorphism. Pharmacogenet Genom 13(8):453–459CrossRef
59.
Houben K, Nederkoorn C, Jansen A (2014) Eating on impulse: the relation between overweight and food-specific inhibitory control. Obesity 22(5):6–8CrossRef
60.
Brunstrom JM, Shakeshaft NG, Scott-Samuel NE (2008) Measuring ‘expected satiety’ in a range of common foods using a method of constant stimuli. Appetite 51(3):604–614CrossRefPubMed
61.
Cappelleri JC, Bushmakin AG, Gerber RA et al (2009) Evaluating the Power of Food Scale in obese subjects and a general sample of individuals: development and measurement properties. Int J Obes 33(8):913–922CrossRef
62.
de Boer SA, Lefrandt JD, Petersen JF, Boersma HH, Mulder DJ, Hoogenberg K (2016) The effects of GLP-1 analogues in obese, insulin-using type 2 diabetes in relation to eating behaviour. Int J Clin Pharm 38(1):144–151CrossRefPubMed
63.
Framson C, Kristal AR, Schenk JM, Littman AJ, Zeliadt S, Benitez D (2009) Development and validation of the mindful eating questionnaire. J Am Diet Assoc 109(8):1439–1444CrossRefPubMedPubMedCentral
64.
van Bloemendaal L, IJzerman RG, Jennifer S et al (2014) GLP-1 receptor activation modulates appetite-and reward-related brain areas in humans. Diabetes 63(12):4186–4196CrossRefPubMed
65.
Batterink L, Yokum S, Stice E (2010) Body mass correlates inversely with inhibitory control in response to food among adolescent girls: an fMRI study. Neuroimage 52(4):1696–1703CrossRefPubMedPubMedCentral

Be confident that your patient care is up to date

Medicine Matters is being incorporated into Springer Medicine, our new medical education platform. 

Alongside the news coverage and expert commentary you have come to expect from Medicine Matters diabetes, Springer Medicine's complimentary membership also provides access to articles from renowned journals and a broad range of Continuing Medical Education programs. Create your free account »