Risultati long-term della terapia medicochirurgica sul controllo metabolico e sul peso corporeo IL COMPORTAMENTO ALIMENTARE E L’ACCUMULO DI TESSUTO ADIPOSO sono REGOLATI da NUMEROSE molecole tra cui: enzimi, ormoni, MEDIATORI e RELATIVI RECETTIORI Badman MK and Flier JS Science 2005 INDICAZIONI ALLA TERAPIA FARMACOLOGICA IMC >30 Kg/m2 IMC >27 Kg/m2 In associazione ad altri fattori di rischio: Senza fattori di rischio o malattie concomitanti • ipertensione arteriosa • dislipidemia • cardiopatia ischemica • diabete mellito di tipo 2 • sleep apnea Farmaci approvati in Italia per il trattamento a lungo termine del sovrappeso-obesità ORLISTAT FDA OKs first obesity drug in 13 years July 17, 2012 Jul 19, 2012 Why New Diet Drugs, Belviq and Qsymia, Are Just in Time The FDA’s approval of the anti-fat pills Qsymia and Belviq provides usable remedies as the number of obese people rises to more than onethird of the U.S. population, and some 300,000 Americans die each year of related complications. Food and Drug Administration (FDA) 27 giugno 2012 15 Luglio 2012 ha approvato l’uso di lorcaserina, un farmaco che agisce sul sistema serotoninergico, e di fentermina -topiramato , una combinazione di un farmaco ad azione noradrenergica e di un farmaco impiegato nel trattamento dell'epilessia e nella profilassi dell'emicrania TRATTAMENTO DELL’ECCESSO PONDERALE pazienti con BMI uguale o superiore a 30 Kg/m2 o pazienti con BMI uguale o superiore a 27 Kg/m2 in presenza di comorbilità. QSYMIA (FENTERMINA-TOPIRAMATO) Fentermina HCl • molecola anoressizzante ad azione noradrenergica (negli USA il più venduto farmaco dimagrante, con circa 6,1 milioni di prescrizioni scritte nel 2009) agisce nelle prime fasi del giorno prontamente assorbita nel tratto gastrointestinale Topiramato farmaco antiepilettico a rilascio controllato DOSI: Unica somministrazione giornaliera fentermina 3,75 mg / topiramato 23 mg fentermina 7,5 mg/topiramato 46 mg fentermina 15 mg/topiramato 92 mg M MGadde Gaddeet etal., al.,Lancet Lancet2011 2011 M Gadde et al., Lancet 2011 profilo lipidico in soggetti con ipertrigliceridemia pressione arteriosa in soggetti ipertesi M Gadde et al., Lancet 2011 profilo glucidico in soggetti con prediabete profilo glucidico in soggetti con diabete M Gadde et al., Lancet 2011 Effetti collaterali M Gadde et al., Lancet 2011 ©2012 by American Society for Nutrition W Timothy Garvey et al., Am J Clin Nutr 2012 Smith et al., NEJM 2010 Smith et al., NEJM 2010 C. Fidler et al., J Clin Endocrinol Metab, October 2011 On 18 October 2012 the Committee for Medicinal Products for Human Use (CHMP) recommend the refusal of the marketing authorisation 21 February 2013 the CHMP re-examined the initial opinion, and confirmed the refusal of the marketing authorisation On Topiramate Fentermina Effects on the heart and blood vessels Depression and anxiety, reduction cognitive effects Liraglutide, analogo once-daily del GLP-1 LIRAGLUTIDE GLP-1 7 Degradazione enzimatica di DPP-4 9 His Ala Glu Gly Thr Phe Thr Ser Asp Val C-16 acido grasso(palmitico) his Ala 7 Glu Gly Thr Phe Thr Ser Val 9 Ser Glu Asp Lys Ala Ala Gln Gly Glu Leu Tyr Ser Glu Ser Lys Ala Ala Gln Gly Glu Leu Tyr Ser Ile Glu 36 Phe Ile Ala Trp Leu Val Lys Gly Arg Gly 37 Phe Ala Trp Leu Val Arg Gly Arg - 97 % omologia con GLP-1; - Formazione in eptameri - Legame reversibile con albumina ; T½=1.5–2.1 min > (T½=13 h) Gly STUDIO SCALE Effect of Liraglutide on body weight in non-diabetic obese subjects or overweight subjects with co-morbidities Number of subjects to be included: Global target 4800 subjects screened 3600 subjects randomised Target in Italy 82 subjects at 7 centres Novo Nordisk Says Trial Shows Victoza Helps Patients Lose Weight Mar 18, 2013 People suffering from type 2 diabetes, the most common form of the disease, LOST 6 PERCENT of their weight when treated with a three-milligram dose of Victoza, a diabetes drug already on the market that isn’t yet approved for weight management, Novo Nordisk said in an e-mailed statement today. NALTREXONE BUPROPIONE Antagonista del R degli oppioidi Antidepressivo • Inibisce il reuptake della dopamina e della noradrenalina Greenway et al., Lancet 2010 A randomized,phase 3 Trial of Naltrexone SR/Bupropion SR on weight and obesity-related risk factors (COR-II). Apovian et al., 2013 Feb 14 [Epub ahead of print] February 1, 2011 F.D.A. Declines to Approve Diet Drug The FDA has declined to approve yet another prescription diet pill, vanquishing nearly any prospect that a new obesity medicine will be available to overweight Americans this year. Orexigen Therapeutics, Inc. (OREX) recently provided an update on its obesity candidate, Contrave. The company, which had received a complete response letter (CRL) from the US Food and Drug Administration (FDA) in Jan 2011 for Contrave, said that it could be in a position to resubmit the NDA for Contrave in the second half of 2013. Table 1. Current status of anti-obesity drugs and drug combinations Name or code Monotherapies Lorcaserin (ADP359) Company Type of agent or combination Current status Arena Pharma 5-HT2C receptor agonist FDA approved 2012, following re- le ATHX-105 Athersys 5-HT2C receptor agonist Phase II BVT.74316 Biovitrum 5-HT6 receptor antagonist Phase I PRX-07034 EPIX Pharma 5-HT6 receptor antagonist Phase I Shinogi Neuropeptide Y5 receptor antagonist Phase II; abandoned 2011 TM30339 7TM Neuropeptide Y4 agonist Phase I Cetilistat Alizyme/Takada Lipase inhibitor Phase III; abandoned? Amylin analogue Amylin Amylinomimetic Phase I KRP-204 Kyorin Selective 3-adrenoceptor agonist Phase II GlaxoSmithKline Sodium glucose transporter-2 (SGLT-2) antagonist Phase I; abandoned 2010 TKS 1225 Thiakis Oxyntomodulin analogue Phase I; sold to Wyeth 2008* SLx-4090 Surface Logix Mitochondrial transfer protein inhibitor Phase II; abandoned 2010 Polytherapies Tesofensine NeuroSearch 5-HT/DA/NA reuptake blocker Phase III Dov 21947 Dov Pharmaceuticals 5-HT/DA/NA reuptake blocker Phase II Obinepitide 7TM Neuropeptide Y2 + Y4 receptor agonist Phase II Contrave Orexigen Bupropion + naltrexone Declined FDA 2011; cardiovascular concerns; company re- le probable Empatic Orexigen Bupropion + zonisamide Phase II Vivus Phentermine + topiramate FDA approved 2012, following re- le Amylin Amylinomimetic/leptin Phase II; programme terminated 2011; antibody generation S-2367 Remogo ozin etabonate (GSK 189075) Qnexa Pramlintide/metreleptin Based on previous research (Cooke and Bloom, 2006; Wilding, 2007; Heal et al., 2009; Sargent and Moore, 2009; Vickers et al., 2 011). This table is not intended as an exhaustive list of all agents in development. *Wyeth have since been bought out by P zer: plans for molecule unknown. DA, dopamine; NA, noradrenaline; 5-HT, 5-hydroxytryptamine. R. John Rodgers et al., Disease Models & Mechanisms (2012) Kirilly et al., Acta Physiologica 2012 Grazie per l’attenzione