Conservative Treatment of Obesity in Patients With T2DM

8/9/2019 Conservative Treatment of Obesity in Patients With T2DM

1/29

in patients with Type 2 Diabetes Me

Conservative treatmentobes

UNIVERSITY OF IOANNINA

FACULTY OF LIFE SCIENCES

DEPARTMENT OF MEDICINE

Georgios Lavasidis

4th

-year student


2/29

Mokdad AMo

Mok

Obesity: Significant risk factor for T2


3/29

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


4/29

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


5/29

Reduced-calorie diet

Physical activity

Lifestyle modification!

Principles and Nonpharmacologic Management of Obesity in Adults, Kushner


6/29

Without lifestyle modification the resumediocre

=224

Randomized trial of lifestyle modification and pharmacotherapy for obesity, Wadden et al, N En


7/29

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


8/29

Physicians contribution is vital

Principles and Nonpharmacologic Management of Obesity in Adults, Kushner

Assess

Advise

Agree

Assist

Arrange


9/29

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



10/29

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


11/29

In Greece (and in Europe) there is only:

Orlistat

FDA approval (new medicines):

Lorcaserin

Phentermine/extended release topiramate

Medicines for obesity



12/29

Orlistat

Pharmacology, H

Gastric and pancreatic lipase inhibitor Reduces TG dissolve in the G

therefore reduces the dietary fat absorption as well


13/29

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)


14/29


15/29

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


Case reports


16/29


17/29

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


18/29

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


19/29

BLOOM-DM Study(RCT)

Secondary results: Lorcaserin and glycemic parameters (decrease

attributed to weight loss)



20/29

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


Under investigation


21/29

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


22/29

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


23/29

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


24/29

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


25/29

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


26/29

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


27/29

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


28/29

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


29/29

Documents

Conservative Treatment of Obesity in Patients With T2DM