obesity
OBESITY
Obesity is having an excessive amount of body fat that may impair health.
The primary cause is an energy imbalance between calories consumed and expended.
Treatment goals include addressing the principal cause of weight gain and focusing management on both weight loss and patient-centered health outcomes.
A multidisciplinary approach, that is a combination of dietary change, physical activity and behavioral modification, is recommended.

Obesity Treatment

Principles of Therapy

Treatment Goals

  • Address the principal cause of weight gain and focus management on both weight loss and patient-centered health outcomes 
  • Short-term goal is loss of 5-10% of body weight over 6 months or may consider a loss of 1 kg/month until ideal body weight
  • Regain of <3 kg in 2 years and sustained reduction of waist circumference of at least 4 cm

Strategy

  • Aim for realistic goals (ie 10% body weight reduction over 6 months or not exceeding 0.5-1 kg/week)
  • Multidisciplinary approach (combination of dietary change, physical activity and behavioral modification) is recommended
    • Intensive lifestyle interventions should be considered in obese patients with T2DM

Pharmacotherapy

  • Pharmacotherapy may aid compliance with dietary restriction, augment diet-related weight loss program, and help achieve weight maintenance after weight loss
  • It may be recommended in patients who failed to achieve meaningful weight loss (ie >5% of total body weight) and to sustain weight loss and for patients with BMI ≥30 or a BMI of ≥27 with presence of risk factors or obesity-related illnesses such as hypertension, dyslipidemia, diabetes mellitus and obstructive sleep apnea
  • Considered in patients who have not lost 1 lb/week after combination with non-pharmacological therapy
  • Check for efficacy and safety at least monthly for the first 3 months of pharmacotherapy
    • Successful pharmacotherapy is considered if at least 2 kg (4.4 lb) weight loss is achieved in the first 4 weeks after starting treatment, otherwise, re-assessment should be considered
  • Pharmacotherapy when used for 6 months-1 year, together with lifestyle modifications and physical activity, produces an average weight loss of 10-15% of initial weight or 2-10 kg
  • For successful weight maintenance, weight regain should be <3 kg (6.6 lb) in 2 years and a sustained reduction in waist circumference of at least 4 cm
  • Since obesity is a chronic disease, some proposes the need for chronic pharmacological therapy; FDA-approved agents for chronic weight management include Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, and Liraglutide
    • If there are no safety concerns with long-term use, continue treatment as long as benefit outweighs risk

Centrally Acting Anti-Obesity Agents

Norepinephrine Agents

  • Eg Phentermine, Diethylpropion, Phendimetrazine, Benzphetamine, Mazindol
  • Enhances catecholamine neurotransmission leading to increased sympathetic activity and reduced appetite
  • Recommended for short-term use (≤12 weeks) because of their stimulant effect on central nervous system
  • Amphetamines are no longer recommended for treatment due to their potential for abuse
  • Some agents (eg Benzphetamine and Phendimetrazine) are considered to be of high potential for abuse and are not recommended
  • Phentermine and Diethylpropion are not recommended in patients with uncontrolled hypertension or a history of heart disease
  • Phentermine
    • Most commonly used noradrenergic agent for the treatment of obesity
    • Does not affect dopamine neurotransmission, hence, little potential for abuse
    • Decreases appetite causing weight loss of 2-10 kg after 12 weeks of use
  • Phentermine/Topiramate
    • Associated with greater mean weight loss than the other weight loss preparations  
    • Perform a pregnancy test prior to therapy and monthly thereafter as fetal toxic effects are linked to Topiramate 

Lorcaserin

  • A 5-HT2C receptor agonist used as an adjunct to lifestyle modifications for weight loss 
  • Withdrawn from the market after a safety clinical trial demonstrated an increased occurrence of cancer in treated patients 

Naltrexone/Bupropion  

  • Naltrexone is an opioid receptor antagonist while Bupropion is a dopamine and norepinephrine reuptake inhibitor
  • Anorectic effect may be a result of sustained activation of anorexigenic neurons in the hypothalamus
  • Reduces food craving

Peripherally Acting Anti-Obesity Agent

Orlistat

  • The only lipase inhibitor approved for management of weight loss
    • Inhibits pancreatic lipase, prevents fat hydrolysis into absorbable fatty acid and thereby decreases fat absorption
  • Indicated for the treatment of obese patients with a BMI of ≥30 kg/m2, or overweight patients with a BMI of ≥28 kg/m2 with associated risk factors, eg type 2 diabetes, hyperlipidemia and hypertension
  • Studies have shown that patients taking Orlistat as part of a nutritional program and physical activity changes had a weight loss of 3.9-10.6 kg after 1 year of treatment and 4.6-7.6 kg after 2 years of treatment
  • When 120 mg is taken immediately before, during or up to 1 hour after each main meal, 1/3 of dietary fat ingested is excreted in stool, reducing fat and calorie intake
    • Also inhibits digestion of TG
    • Current data noted rare cases of severe liver injury with the use of this medication
  • Can be used for long-term (up to 4 years) weight management

Others

Antidiabetic Medications

  • Eg glucagon-like peptide-1 (GLP-1) receptor agonists, eg Liraglutide; sodium-glucose linked transporter-2 (SGLT-2) inhibitors
  • Indicated in patients with T2DM who are overweight or obese
  • Promote weight loss, reduce visceral adipose tissue, and prevent weight regain
  • Liraglutide can be used for weight management up to 2 years
  • Consider giving Metformin and psychological therapy for weight gain prevention to patients with severe mental illness who are receiving antipsychotic drugs associated with weight gain 

Lisdexamfetamine and Topiramate

  • Considered as adjunctive therapeutic agents to psychological treatment in overweight or obese patients with binge-eating disorder

Dietary Supplements and Herbal Preparations

  • Not recommended for the treatment of obesity due to insufficient evidence
  • May contain unpredictable amount of active ingredients, have unpredictable efficacy and unknown safety profiles

Non-Pharmacological Therapy

Behavioral Therapy

  • Provides methods to overcome barriers to weight loss (ie socio-cultural beliefs, stress, denial), such as motivational counseling
  • Should include counseling, self-monitoring, portion control, stimulus control, contingency management, stress management, cognitive behavioral strategies and weight loss support groups
  • If weight loss of 2.5% within the 1st month of treatment was not achieved, intensification of behavioral intervention and support should be done 
  • There is evidence supporting that intensive, multicomponent behavioral interventions for obese patients can improve glucose tolerance and other physiologic factors for cardiovascular disease
  • Information and communication technology (ICT)-based weight loss tools (eg structured websites, internet-enabled mobile phone applications) which allow patients to track and monitor their behaviors online compared to standard non ICT-based interventions were found to significantly increase weight loss, decrease total energy and saturated fat intake, and have minimal but positive effect on physical activity
    • ICT-based interventions must include the following treatment components: Tailoring, goal setting, self-monitoring, social support and targeted feedback

Comorbidities

  • Prevention and treatment of comorbidities are recommended
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