obesity
OBESITY
Obesity is the accumulation of abnormal or excessive body fat that presents as a risk to health.
Primary cause is a chronic 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

  • To reduce health risks and improve health 
  • 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 5-15% of body weight over 6 months with long-term goal of weight maintenance 
    • Depends on the severity of obesity and obesity-related comorbidity (ORC), eg poorly controlled DM despite best medical treatment, nonalcoholic steatohepatitis and obstructive sleep apnea may require ≥10% weight loss
  • 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 interventions should be considered in obese patients with T2DM or poorly controlled ORC (eg use of very low-calorie diet, anti-obesity agents or bariatric metabolic surgery) 

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 kg/m2 or a BMI of ≥27 kg/m2 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

Liraglutide

  • A glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of diabetes that was found to be associated with weight loss 
    • Acts centrally through the GLP-1 receptors in the brain to increase postprandial satiety and to decrease hunger and prospective food intake 
  • Liraglutide can be used for weight management for up to 2 years

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

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
    • Use with caution in patients with anxiety disorders and closely monitor for changes in behaviors and moods
    • Severe mental depression may result from abrupt discontinuation after prolonged high-dose intake; it is recommended to gradually withdraw Phentermine therapy
  • 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 

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

  • Indicated in patients with T2DM who are overweight or obese 
  • The following antidiabetic agents can be considered in patients with T2DM and overweight/obesity as they can cause weight loss: Metformin, sodium-glucose linked transporter 2 (SGLT2) inhibitors and GLP-1 receptor agonists 
    • Dipeptidyl peptidase-4 (DPP-4) inhibitors and Acarbose are weight neutral
  • Promote weight loss, reduce visceral adipose tissue, and prevent weight regain
  • 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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