Obesity Treatment

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 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-HT_2C 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

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