conservative treatment of obesity in patients with t2dm
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in patients with Type 2 Diabetes Me
Conservative treatmentobes
UNIVERSITY OF IOANNINA
FACULTY OF LIFE SCIENCES
DEPARTMENT OF MEDICINE
Georgios Lavasidis
4th
-year student
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Mokdad AMo
Mok
Obesity: Significant risk factor for T2
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BMI and T2DMObesity (BMI 30)
Increased adipose tissue(endocrine-secretory organ)
Increased release of insulinresistance-provoking
adipokines (e.g. TNF-a andIL-6)
Decreased insulin sensitivity
Impaired glucose tolerance
Treating Diabetes and Prediabetes by Focusing on Obesity Management, Khaodhiar et
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Lifestyle modification
andCOMPLEMENTARY
Drug treatment
Conservative treatment of obesity
The pharmacological and surgical management of adults with obesity, Rya
Randomized trial of lifestyle modification and pharmacotherapy for obesity, Wadden et al, N En
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Reduced-calorie diet
Physical activity
Lifestyle modification!
Principles and Nonpharmacologic Management of Obesity in Adults, Kushner
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Without lifestyle modification the resumediocre
=224
Randomized trial of lifestyle modification and pharmacotherapy for obesity, Wadden et al, N En
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Look AHEAD (RCT)
In
diab
ed
N
ob
ca
ev
=5145
Follow-up:
10
Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes, Look AHEAD Research Group, N
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Physicians contribution is vital
Principles and Nonpharmacologic Management of Obesity in Adults, Kushner
Assess
Advise
Agree
Assist
Arrange
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As an adjunct to lifestyle interventions in patients with:
BMI 30 or
BMI 28 (27 for new medicines) with risk factors like:
T2DM
Hypertension
Dyslipidemia
Cardiovascular disease
Fatty liver disease
Obstructive sleep apnea
Drug treatment
The pharmacological and surgical management of adults with obesity, Rya
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Clinically-meaningful weight loss (5%) in one year
The results in the first12 weeks are predictive for thoutcome, thus the continuation or discontinuation omedicine is decided at this point
Targets
Long-term drug treatment for obesity: a system atic and clinical review, Yanovski
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In Greece (and in Europe) there is only:
Orlistat
FDA approval (new medicines):
Lorcaserin
Phentermine/extended release topiramate
Medicines for obesity
The pharmacological and surgical management of adults with obesity, Rya
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Orlistat
Pharmacology, H
Gastric and pancreatic lipase inhibitor Reduces TG dissolve in the G
therefore reduces the dietary fat absorption as well
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XENical in the prevention of diabetes in obese subjects (XENDOS) study: a ra ndomized s
changes for the prevention of type 2 diabetes in obese patients, Torgeson et a
N=3305
Follow-up:
4 years
XENDOS Study(RCT Orlistat+lifestyle vs. Placebo+lifestyle)
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Generally severe side effects are not common, howeare reports of:
Gastrointestinal disorders (very common, usual reason for trediscontinuation)
Headache, infections (very common)
Possible nephrotoxicity (Coutinho et al, 2013)
Hepatotoxicity in rare cases
The only anti-obesity drug indicated in adolescents
Safety
The pharmacological and surgical management of adults with obesity, Rya
Case reports
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Activation of 5-2C receptors on POMC neurons in arcuate n
hypothalamus
a-MSH release
Activation of MC4R in paraventricular nucleus
Feeling of satiety and appetite reduction
Mechanism of action
Lorcaserin: A novel antiobesity drug, Brashier et al, J Pharma
Lorcaserin for the treatment of obesity, Redman e t al, Drug
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BLOOM-DM Study(RCT)
N=604
patients
with T2DM
Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study, O'Neil et al, Obesit
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BLOOM-DM Study(RCT)
Secondary results: Lorcaserin and glycemic parameters (decrease
attributed to weight loss)
Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study, O'Neil et al, Obesit
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Well tolerated in general. Major side effects:
Headache (14-17%) Hypoglycemia in diabetics taking metformin (13%)
Back pain (11%)
Nasopharyngitis (11%)
Valvulopathies (5-2B)
Psychiatric disorders
Carcinogenesis
Serotonin syndrome
Safety
Lorcaserin: A novel antiobesity drug, Brashier et al, J Pharma
Lorcaserin for the treatment of obesity, Redman et al, Drug
Belviq, INN-Lorcaserin S
Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study, O'Neil et al, Obesit
Under investigation
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FDA approval: 2012
Phentermine:
In the USA it is also used as monotherapy for short-term obetreatment
Centrally acting sympathomimetic medicine
Upregulation of dopamine, noradrenaline, and serotonin actiappetite suppression
Increased energy expenditure
Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate, Sweeting et al, Diabetes M
Phentermine/Extended release topira
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Topiramate:
It is used as an antiepileptic and antimigraine medicine
GABA-agonist
Unclear mechanism of action
Increased energy expenditure, calorie intake reduction
Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate, Sweeting et al, Diabetes M
Medical treatment of obesity: the past, the present and the future, Bray GA, Best Pract Res Cli
Phentermine/Extended release topira
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EQUIP Study(RCT)
Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP), Allison et al, Obesit
N=126
The following were compared:
1. Phentermine/Topiramate-ER (high dose)
2. Phentermine/Topiramate-ER (low dose)
3. Placebo
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Major side effects:
Dry mouth
Constipation
Paresthesia
Dysgeusia
Insomnia
Dizziness
Contraindications: hyperthyroidism and glaucoma
Teratogenic (topiramate)
Safety
5%
Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate, Sweeting et al, Diabetes
The combination redu
thus the side effects,
separately
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Percentage of patients with 5% weight loss by med
Orlistat: 35-73%
Lorcaserin: 37-47%
Phentermine/Topiramate-ER (high dose): 67-70%
Comparison
Long-term drug treatment for obesity: a system atic and clinical review, Yanovski
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Sibutramine
Serotonin-noradrenaline reuptake inhibitor
Withdrawn in 2010 because of cardiovascular events (nonfatastroke SCOUT study)
Rimonabant
Cannabinoid-1 receptor antagonist
Withdrawn in 2008 because of psychiatric dissorders (mainly incidents of suicides were reported)
Old medicines
P
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The results are modest in comparison with the genepopulation:
Insulin and other antidiabetic drugs induce weight gain
Psychological reasons (long history of unsuccessful weight losintervention attempts)
Difficulties in exercise because of T2DM complications (arterineuropathy, heart disease)
Obesity treatment in patients with T
Weight loss in type 2 diabetic patients, Pi-Sunyer FX
Managing type 2 diabetes: balancing HbA1c and body weight, Mavian et al, P
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Obesity is an important risk factor for T2DM Conservative treatment of obesity includes lifestyle intervent
medicines
The only available drug for obesity in Europe isorlistat
In the USA there are alsolorcaserin andphentermine/topiram
The recent withdrawal of two drugs because of severe side efindicates the need for continuous safety check
The results of the treatment in diabetic patients are worse thgeneral population
Conclusions
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