obesity
OBESITY
Obesity is having an excessive amount of body fat in relation to lean body mass that may impair health.
The primary cause is an energy imbalance between calories consumed and expended.
Treatment goals include to lose 5-10% of body weight or 0.5-1 kg (1-2 lb)/week for 6 months and regain of <3 kg in 2 years and sustained reduction of waist circumference of at least 4 cm.
Strategies are aiming for realistic goals and a multidisciplinary approach that is a combination of dietary change, physical activity and behavioral modification.

Principles of Therapy

Treatment Goals

  • Loss of 5-10% of body weight or 0.5-1 kg (1-2 lb)/week for 6 months
  • 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)
  • Multidisciplinary approach (combination of dietary change, physical activity and behavioral modification) is recommended

Pharmacotherapy

  • Pharmacotherapy may aid compliance with dietary restriction, augment diet-related weight loss program, and to achieve weight maintenance after weight loss
  • Pharmacotherapy 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, DM and obstructive sleep apnea
  • Considered in patients who have not lost 1 lb/week after combination of non-pharmacological therapy
  • Check for efficacy and safety at least for the first 3 months of pharmacotherapy is suggested
  • 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
  • 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
  • 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, Lorcaserin, Phentermine/Topiramate, Naltrexone/Bupropion, and Liraglutide
  • The long-term safety of Phentermine and other anorexiants, as well as Orlistat, is unknown; more studies need to be done
  • There is limited data on the efficacy and safety of combination of anti-obesity drugs

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 5HT-serotonin antagonist, Lorcaserin has a low rate of adverse events and is well tolerated
    • Avoid use with monoamine oxidase inhibitors due to the risk of serotonin syndrome 
  • Used in patients with CVD who need weight loss medication  

Naltrexone/Bupropion  

  • Naltrexone is an opioid antagonist while Bupropion is a dopamine and norepinephrine reuptake inhibitor
  • Reduces food craving

Peripherally Acting Anti-Obesity Agent

Orlistat

  • The only lipase inhibitor approved for management of weight loss
  • Also indicated in patients with CVD who needs pharmacological therapy for weight loss
  • 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
  • Inhibits pancreatic lipase, prevents fat hydrolysis into absorbable fatty acid and thereby decreases fat absorption
  • 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, and decreases the absorption of vitamins A, D, E and K
    • Current data noted rare cases of severe liver injury with the use of this medication

Others

Antidiabetic Medications

  • Eg glucagon-like peptide-1 (GLP-1) analogs, eg Liraglutide; sodium-glucose-linked transporter-2 (SGLT-2) inhibitors
  • Indicated in patients with type 2 diabetes who are overweight or obese
  • Promote weight loss and reduce visceral adipose tissue

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)
  • Should include counseling, self-monitoring, portion control, stimulus control, contingency management, stress management, cognitive behavioral strategies, 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 CVD

Comorbidities

  • Prevention and treatment of comorbidities are recommended
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