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