Lorcaserin (Belviq ) Rimonabant 2008 Sibutramine (Reductil, ) (World Health organization, WHO) 1996 WHO Orlistat (Xenical, )
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1 (World Health organization, WHO) 1996 WHO (Body mass index, BMI)2427 kg/m 2 27 kg/m 2 25% 30% %(48.9%38.3%) (AACE/ACE) BMI 27 kg/m 2 BMI 35 kg/m 2 (The Food and Drug Administration, FDA)1992 fenfluramine/ phentermine Rimonabant 2008Sibutramine (Reductil, ) Orlistat (Xenical, ) FDA (1) (2) 35% 2 FDA Lorcaserin (Belviq, 2012 ) Topiramate/Phentermine (Qsymia, 2012 )Naltrexone/bupropion (Contrave, 2014 )Liraglutide (Saxenda, 2014) Lorcaserin (Belviq, ) Lorcaserin (Belviq, 2012 ) Topiramate/ Phentermine (Qsymia, 2012) Naltrexone/ bupropion (Contrave, 2014 ) Lorcaserin (Belviq ) Lorcaserin
2 Phentermine5-HT2A 5-HT2B 5-HT2C Lorcaserin (pro-opiomelanocortin, POMC) 5-HT2C -MSH(melanocyte stimulating hormone) (cocaine-amphetamine regulated transcript, CART) (paraventricular nucleus) Lorcaserin5-HT2Creceptor BLOSSOM, BLOOM and BLOOM-DM 2,3 BLOSSOM(4008)BLOOM(3182 ) Lorcaserin 10mgQD, 10mg BID 52.4%5%20.2% 10% (BLOOM-DM)Lorcaserin (HbA1C) Bridging study 4 (1) % 22.7% LDL FDA 2 () 2 () Lorcaserin 10mg12 5% Lorcaserin (16%)(13%) (8%) 5 (neuroleptic malignant syndrome) Topiramate / Phentermine (Qsymia ) 36
3 (Norepinephrine) Phentermine m 37.5mgPhentermine Topiramate (voltage-dependent sodium channels)gaba (dose-dependent) Topiramate 6 CONQUER 7 EQUISEQEL 8 CONQUER 2487 BMI kg/m 2 2 phentermine 7.5 mg/topiramate 46 mgphentermine 15 mg/ topiramate 92 mg 5%62% 70%10% 37%48% CONQUER2 SEQEL 10.5% FDABMI30 kg/m 2 ()27kg/m 2 () phentermine3.75 mg/ topiramate23 mg2 phentermine 7.5 mg/topiramate 46 mg % phentermine 15 mg/topiramate 92 mg 125% (20%) (21%)(17%)(19.9%) (10.6 %)(9.4 %)(9%) /14 MAOI Bupropion/naltrexone, Contrave Bupropion 9 Bupropion
4 POMC (-melanocyte stimulating hormone,-msh ) (-endorphin)-msh (paraventricular nucleus)4 (melanocortin-4 receptor (MC4R)) Naltrexoneopioid antagonist -endorphinpomc (inhibitory -opioid receptor (MOP-R))POMC NaltrexoneMOP-R antagonistpomc Contrave COR-I 10 COR-IICOR- BMODCOR-DiabetesCOR-I BMI30 45 kg/m² BMI kg/m² naltrexone 32 mg/bupropion 360mg naltrexone 16 mg /bupropion 180mg 5% 39%48% 10%20% 25% Naltrexone/bupropion for obesity: An investigational combination pharmacotherapy for weight loss. Pharmacological Research 84 (2014) 1 11 Naltrexone/Bupropion FDA BMI30 kg/m 2 27 kg/ m 2 ( ) Naltrexone/Bupropion 8/90 mg
5 212 5% (33%) (19%)(18%)(11%)(10%) ( 0.6mmHg)(1 beat/min) GABA 14 (MAOI) Liraglutide, Saxenda Victoza Liraglutide 1.8mg/day 3mg/day (Incretin) Glucagonlike peptide-1(glp-1) Glucose-dependent insulinotropic polypeptide (GIP) GLP-1GLP-1 Liraglutide GLP-1 agonist SCALE MaintenanceSCALE Diabetes SCALE Obesity and PrediabetesSCALE Obesity and Prediabetes BMI30 kg/m²bmi27 kg/m² Liraglutide 3mg Liraglutide 3mg3 5%49.6% 10%24.8% SCALE Diabetes 12 Liraglutide(3.0mg) Liraglutide(1.8 mg) Sulfonylurea FDA BMI30 kg/ m 2 ()27 kg/m 2 ( ) 0.6mg/day 0.6mg3.0mg
6 16 4% (39.3 %) (15.7%)(13.6 %)(23 %) 2(MEN II) liraglutide?? (JAMA) Phentermine/topiramateLiraglutide Naltrexone/bupropionLorcaserinOrlistat 5% Phentermine/topiramate Lorcaserin AACE/ACE2016 AACE/ACE (BMJ) (RR= 0.82, 95% CI ) 3-10% FDAOrlistat (Xenical, ) Lorcaserin (Belviq, ) Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events A Systematic Review and Meta-analysis. JAMA June 14, 2016 Volume 315, Number
7 1. W. Timothy Garvey, MD, FACE; Jeffrey I. Mechanick, MD, FACP, FACE, FACN, ECNU; Elise M. Brett, MD, FACE, CNSC, ECNU, et al: comprehensive Clinical practice guidelines for medical care of patients with obesity. AACE/ACE Aronne L, Shanahan W, Fain R, et al: Safety and efficacy of lorcaserin: a combined analysis of the BLOOM and BLOSSOM trials. Postgrad Med 2014; 126: O'Neil PM, Smith SR, Weissman NJ, et al: Phentermine/ Topiramate ER Naltrexone ER/ Bupropion ER Liraglutide Xenical Belviq Qsymia Contrave Saxenda, 13, 12, 11, mg 20 mg 7.5 mg/ 15 mg/ 46 mg 92 mg 32 mg/360 mg 3 mg (%) (kg) (cm) n/a n/a BMI (%) (%) ITT LOCF %(in %) ITT LOCF %(in %) 28.6 ITT LOCF comprehensive Clinical practice guidelines for medical care of patients with obesity AACE/ACE ITTintent-to-treat () LOCFlast observation carried forward () Orlistat Locaserin
8 Belviq Qsymia Contrave Saxenda Lorcaserin Topiramate 5HT-2C agonist Bupropion ER Liraglutide Noradrenalin GLP-1 analog Dopamine and Noradrenaline convulsant reuptake inhibitors ( ) (MAOI) GABA (MAOI) Liraglutide X X comprehensive Clinical practice guidelines for medical care of patients with obesity AACE/ACE
9 Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring) 2012; 20: Belviq Taiwan Bridging Study Greenway FL, Shanahan W, Fain R, et al: Safety and tolerability review of lorcaserin in clinical trials. Clin Obes 2016; 6: ; 30(4): 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 2011; 377: Garvey WT, Ryan DH, Look M, 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 Feb; 95(2): Sonja K. Billes a, Puspha Sinnayahb, Michael A. Cowleyc. Naltrexone/bupropion for obesity: An investigational combination pharmacotherapy for weight loss. Pharmacol Res 2014; 84: Prof Frank L Greenway, MD, Ken Fujioka, MD, Prof Raymond A Plodkowski, MD, et al: Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2010; 376: 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 randomized, double-blind trial. Lancet 2017; 389: 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: Rohan Khera, MD; Mohammad Hassan Murad, MD, MPH; Apoorva K. Chandar, MBBS, MPH et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events A Systematic Review and Meta-analysis. JAMA 2016; 315: Chenhan Ma,1 Alison Avenell,1 Mark Bolland, et al: Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ 2017; 359: j
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