Conseguenze cardiovascolari e pressorie della chirurgia bariatrica

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