medikamente in der adipositastherapie

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Medikamente in der Adipositastherapie

Eine Chance mit Nebenwirkungen?Dr. Clarence P. DavisBergstrasse 8CH-8702 Zollikon

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Dr. C.P. DavisThemenDefinition, Epidemiologie und Pathogenese der AdipositasAdipositastherapie: Indikation, BehandlungsstrategienErnhrungstherapiePharmakotherapieVerhaltensmodifikation

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Dr. C.P. DavisDefinition der AdipositasAdipositas (Fettsucht, engl. Obesity)

ist gekennzeichnet durch eine kritische Vermehrung der Fettmassedie schliesslich zu ernsthaften Gesundheitsstrungen fhrt. ist eine chronische Erkrankungdie zur Behandlung, ein individuelles, langfristiges und komplexes therapeutisches Programm erfordert

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Dr. C.P. DavisKlassifikation der Adipositas[Grsse (m)]2Gewicht (kg)BMI=

Normalgewicht: BMI 18.5-24.9bergewicht: BMI>25

BMI 25-29.9 Pr-AdipositasBMI 30-34.9 Adipositas Klasse 1BMI 35-39.9 Adipositas Klasse 2BMI >40Adipositas Klasse 3

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Dr. C.P. DavisRisikoKlassifikationBMI kg/m2Risiko von Begleiterkrankungen*Taillenumfang102 cm (Mnner) 88 cm (Frauen)Untergewicht40.0Sehr hochSehr hoch*bezogen auf Normalgewicht und normalen Taillenumfang , Krankheitsrisiko fr Typ-2-Diabetes, Hypertonie und KHK.

NIH/NHLBI The Practical Guide, Identification, Evaluation and Treatment of Overweight and Obesity in Adults, October 2000.

6WHR >=1 fr Mnner, >=0.8 fr Frauen erhhtes Risiko

Dr. C.P. Davis19961991

Obesity Trends* Among U.S. AdultsBRFSS, 1991, 1996, 2004

(BMI 30)No Data or = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.

Publication Types: Meta-Analysis

PMID: 11169969 [PubMed - indexed for MEDLINE]

Dr. C.P. DavisEinfluss eines normalen BMI auf die Krebshufigkeit in EUIn Europa knnten jhrlich ca. 70000 Krebsflle verhindert werden, wrden die Leute einen normalen BMI von /=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS: Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). CONCLUSIONS: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].

Publication Types: Clinical Trial Randomized Controlled Trial

PMID: 14693982 [PubMed - indexed for MEDLINE]

Dr. C.P. DavisXenical ZusammenfassungIn der DiabetesprophylaxeSignifikant weniger Typ 2 Diabetes:Xenical senkt das relative Risiko, an T2D zu erkranken, um 37%Bei Patienten mit Typ 2 Diabetes, die mit SH, Metformin oder Insulin behandelt werden, hat Xenical gezeigt, dass es:die Gewichtsreduktion verbessertdie glykmische Kontrolle verbessertdie metabolischen Risikofaktoren verbessertHufige Nebenwirkungen:Weiche Sthle, hufigere Stuhlfrequenz, Meteorismus, SteatorrhoeVerminderte Absorption fettlslicher Vitamine bei 5-15% der Patienten (klinische Bedeutung unklar!)

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Dr. C.P. DavisReductil im berblick1988Erste Prsentation von klinischen Daten zu Sibutramin und Depression1991Erste Prsentation von klinischen Daten zu bergewicht1997Erstzulassung von Reductil in den USA1999Einfhrung von Reductil in der Schweiz2006Kassenzulssigkeit fr BMI > 35

15 Millionen Patienten weltweit mit Reductil behandelt

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Dr. C.P. DavisWirkmechanismus: Reuptake InhibitorAdaptiert von Ryan et al. Obesity Res. 1995;3(suppl 4):553S559S.

RascheresSttigungsgefhl

Noradrenalin

Serotonin

MAOCatabolismReleaseMAOCatabolism

S

Release

S

S

SSibutraminNoradrenalinSerotonin

S

REUPTAKEREUPTAKEGesteigerterGrundumsatzEssen von Kohlehydraten

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Dr. C.P. DavisReductil: Langzeitgewichtsreduktion

0-2-4-6-8-10-16-12-141-1023Treatment Month*p85% of the weight loss achieved at the end of the open weight loss phase. [[Reference James]]

Lancet. 2000 Dec 23-30;356(9248):2119-25.Related Articles, Links Comment in: Lancet. 2001 Apr 21;357(9264):1287-8. Lancet. 2001 Apr 21;357(9264):1287; author reply 1288.

Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance.

James WP, Astrup A, Finer N, Hilsted J, Kopelman P, Rossner S, Saris WH, Van Gaal LF.

Rowett Research Institute, Aberdeen, UK. [email protected]

BACKGROUND: Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and to enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 2 years. METHODS: Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates. 467 (77%) patients with more than 5% weight loss were then randomly assigned 10 mg/day sibutramine (n=352) or placebo (n=115) for a further 18 months. Sibutramine was increased up to 20 mg/day if weight regain occurred. The primary outcome measure was the number of patients at year 2 maintaining at least 80% of the weight lost between baseline and month 6. Secondary outcomes included changes in uric acid concentrations and glycaemic and lipid variables. Analysis was by intention to treat. FINDINGS: 148 (42%) individuals in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 sibutramine-treated individuals who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 individuals in the placebo group (odds ratio 4.64, p102 cm (40 in) for men and >88 cm (35 in) in women, i.e. the diagnostic criterion for abdominal obesity defined by NCEP/ATP III.1 In addition, in RIO Diabetes the patients had a average HbA1c of 7.5% at screening and the time since diabetes diagnosis was 5 years . The mean age in the four studies were 45-56 years (45 years in RIO NA and EU, 48 years in RIO Lipids and 56 years in RIO Diabetes). The number of patients completing 12 month of the study varied between 53-66%.

1. National Cholesterol Education Program. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Institutes of Health/National Heart Lung and Blood Institute. Available at www.nhlbi.nih.gov/guidelines/cholesterol.

Dr. C.P. Davis

Rimonabant: Vernderung des HftumfangsPooled data from:L.Van Gaal, Lancet 2005; 365: 1389-97, X. Pi-Sunyer, Circulation 2005:111(13);1727Circulation 2005, JP. Desprs, Int J. Obes. Relat Metab Disod 2004, 28 (Suppl1) pS28; T5:O2-005-10-8-6-4-200481216202428323640444852LOCF

-4.5cm* -8.5cm*

Waist circumference change (cm)Weeks

* For RIO EU, completersRIO~EuropePlacebo

R 20 mg

RIO~LipidsPlacebo

R 20 mg

RIO~NAPlacebo

R 20 mg

122Consistent changes in WC Abdominal obesity, as measured by high waist circumference, is known to predict the risk of metabolic abnormalities and CVD beyond BMI.1 The health threat posed by abdominal obesity is largely due to excess intra-abdominal adiposity, which plays a major role in the development of dyslipidaemia, metabolic syndrome, insulin resistance, type 2 diabetes, inflammation and thrombosis all factors leading to cardiovascular disease.The effects of rimonabant on waist circumference in RIO-Lipids, RIO-North America and RIO-Europe were highly consistent, with an overall mean reduction from baseline of approximately 8.5 cm in patients receiving rimonabant 20 mg for 1 year (p 35.012.677.5920.138.8Taillenumfang80909511273879511112.13.25.711.52.66Leibliche ElternLeibliche MtterLeibliche Vter22.52423.525.22525.524.826AdoptivmtterAdoptivvter23.82524.225.224.524.923.8924.2Gewichtszunahme1213.615.415.9Essens-Portionen1977 - 19781989 - 19911994 - 1996Salzsnacks132199225Desserts316334357Softdrinks144157193Fruchtsfte139152189Pommes Frittes188247256Hambuger389392486Kseburger397547533Pizza487556476Mexikanisch408446541

Tabelle100000

Relative Risk of Type 2 Diabetes among Women in the NHI

Tabelle200000000

Taillenumfang (cm)RRNHANES III Survey

Tabelle300000000

AdoptivmtterAdoptivvter

000000000

2Baseline fast-food frequency (times per week)Weight gain (kg)15-year change in fast-food frequency (times per week)3'031 Personen, 18-30 Jahre, 15 Jahre Beobachtung

000000000000000000000000000

1977 - 19781989 - 19911994 - 1996Energy Intake, kcalTrends in Energy Intake

Diagramm511.811.913.612.513.215.413.413.815.9


Tabelle1BMI< 23.023.0-24.925.0-29.930.0-34.9> 35.012.677.5920.138.8Taillenumfang80909511273879511112.13.25.711.52.66Leibliche ElternLeibliche MtterLeibliche Vter22.52423.525.22525.524.826AdoptivmtterAdoptivvter23.82524.225.224.524.923.8924.2Gewichtszunahme1213.615.415.9

Tabelle1


Tabelle2


Tabelle3



Diagramm711.661.842.162.87

TV-StundenRR37918 nicht diabetische MnnerFragebogen, 10 Jahre Follow-up

Tabelle1BMI< 23.023.0-24.925.0-29.930.0-34.9> 35.012.677.5920.138.8Taillenumfang80909511273879511112.13.25.711.52.66Leibliche ElternLeibliche MtterLeibliche Vter22.52423.525.22525.524.826AdoptivmtterAdoptivvter23.82524.225.224.524.923.8924.2Gewichtszunahme1213.615.415.9Essens-Portionen1977 - 19781989 - 19911994 - 1996Salzsnacks132199225Desserts316334357Softdrinks144157193Fruchtsfte139152189Pommes Frittes188247256Hambuger389392486Kseburger397547533Pizza487556476Mexikanisch408446541TV-und Diabetesbis 112-101.6611-201.8421-402.16>402.87

Tabelle100000


Tabelle200000000


Tabelle300000000


000000000


000000000000000000000000000

1977 - 19781989 - 19911994 - 1996Energy Intake, kcalTrends in Energy Intake

00000

TV-StundenRR37918 nicht diabetische Mnner, Fragebogen, 10 Jahre Follow-up

Diagramm81.42.43.24.23.81.62.12.42.831.91.82.432.31.723.222.611.73.41.82.2

>3019-308.25-18.751.75-8.03019-308.25-18.751.75-8.03019-308.25-18.751.75-8.03019-308.25-18.751.75-8.0

medikamente in der adipositastherapie

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