Obesity Management

Principles of Therapy

Treatment Goals  

The treatment goals in managing obesity are to reduce health risks and improve health, by preventing further weight gain and obesity-related complications, preventing, or managing existing comorbidities, and restoring positive body image and self-esteem. It is also important to address the principal cause of weight gain (treat primary and secondary causes of obesity) and focus management on both weight loss and patient-centered health outcomes (eg improved mental wellbeing, physical and social functioning, and fitness). 

The short-term goal is a loss of 5-15% of body weight over 6 months with long-term goal of weight maintenance. Depending on the severity of obesity and obesity-related comorbidities, eg poorly controlled diabetes mellitus despite best medical treatment, nonalcoholic steatohepatitis and obstructive sleep apnea may require ≥10% weight loss. The regain of <3 kg in 2 years and sustained reduction of waist circumference of at least 4 cm are also essential.  

Strategy  

It is important to aim for realistic goals (ie 10% body weight reduction over 6 months or not exceeding 0.5-1 kg/week) to maintain weight and prevent weight gain. Multidisciplinary approach (combination of dietary change, physical activity, and behavioral modification) is recommended. Intensive interventions should be considered in obese patients with type 2 diabetes mellitus or poorly controlled obesity-related comorbidities (eg use of very low-calorie diet, anti-obesity agents, or bariatric metabolic surgery). Reduction of the global cardiovascular risk (eg diet modification, physical activity, weight loss, smoking cessation and control of blood glucose, blood pressure, and serum lipids) should be undertaken by patients with obesity and type 2 diabetes mellitus or hypertension.  

Advantages of Weight Loss  

Weight loss promotes reduction in blood pressure, lipid levels (eg total cholesterol, TG, and LDL), risk of type 2 diabetes mellitus and all-cause mortality. The goal is a decrease in blood pressure by <130/80 mmHg, an LDL of <3.4 mmol/L, and fasting blood glucose of ≤6 mmol/L. Since the improvement in LDL-C is modest with weight loss, CVD risk may be reduced with early interventions that prevent and/or treat excess adiposity and increased levels of atherogenic cholesterol (eg LDL-C and/or non-HDL-C).

Weight loss also improves the patient’s cardiovascular disease risk profile with weight loss of >10-15%, produces clinical benefits in obesity-related comorbidities such as diabetes mellitus prevention or remission, ovulation, and regularization of menses in polycystic ovarian syndrome, reduction in inflammation and fibrosis in MAFLD, improved symptomatology in obstructive sleep apnea, osteoarthritis, urinary stress incontinence, asthma, and gastroesophageal reflux disease.  

Pharmacological therapy

Pharmacotherapy may aid compliance with dietary restriction, augment diet-related weight loss program, and help achieve weight maintenance after weight loss. The risks, side effects, previous obesity treatments, and patient preferences are considered when choosing therapeutic options. 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 the presence of risk factors or obesity-related illnesses such as hypertension, dyslipidemia, diabetes mellitus, and obstructive sleep apnea. The greatest effect of anti-obesity medications is on reducing TG levels with neutral to increases in HDL-C levels and marginal reductions in LDL-C levels. It is also considered in patients who have not lost 1 lb/week after combination with non-pharmacological therapy.

It is important to check for the 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 to 1 year, together with lifestyle modifications and physical activity, produces an average weight loss of 3.1-8.4% above placebo. 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 proposed the need for chronic pharmacological therapy. The United States Food and Drug Administration (US FDA)-approved agents for chronic weight management include Orlistat, Phentermine or Topiramate, Naltrexone or Bupropion, Liraglutide, Semaglutide, and Tirzepatide. If there are no safety concerns with long-term use, continue treatment as long as benefit outweighs risk. It is important to prioritize the treatment of acute illness (eg markedly increased blood glucose and/or blood pressure, severe dyslipidemia, acute thrombosis, cardiovascular disease, or cancer) with concomitant treatment of obesity. Medications which are not associated with weight gain for the treatment of other health conditions must be chosen.  

Centrally Acting Anti-Obesity Agents¹  

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists  

Example drugs: Liraglutide, Semaglutide  

GLP-1 receptor agonists are approved for the treatment of diabetes and were found to be associated with weight loss. They act centrally through the GLP-1 receptors in the brain to induce postprandial satiety and to decrease hunger and prospective food intake.  

They may be used as adjunct to a reduced calorie diet and increased physical activity for chronic weight management of patients with a BMI of ≥30 kg/m², or patients with a BMI of ≥27 kg/m² to <30 kg/m² with at least 1 weight-related comorbidity (eg type 2 diabetes, dyslipidemia or hypertension).  

Liraglutide can be used for weight management for up to 2 years. Liraglutide reduced HbA1c, blood pressure, insulin resistance, lipid levels, risk of stroke and the use of oral glucose lowering agents in patients with type 2 diabetes mellitus. Studies showed a statistically significant reduction in body weight after 68 weeks of treatment with Semaglutide compared with placebo. Semaglutide reduces HbA1c, blood pressure, lipid levels, and the risk of stroke.  

GLP-1 Receptor and Glucose-dependent Insulinotropic Polypeptide (GIP) Receptor Agonist  

Example drug: Tirzepatide  

Tirzepatide is indicated for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial BMI of ≥30 kg/m² or ≥27 kg/m² with at least 1 weight-related comorbid condition (eg hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea, or cardiovascular disease). Patients are advised regarding the potential risk of medullary thyroid carcinoma and symptoms of thyroid tumors.  

Naltrexone or Bupropion  

Naltrexone is an opioid receptor antagonist while Bupropion is a dopamine and norepinephrine reuptake inhibitor. They are adjuncts to a reduced-calorie diet and increased physical activity for weight management of patient with a BMI of ≥30 kg/m² or ≥27 kg/m² with at least 1 weight-related comorbid condition (eg type 2 diabetes mellitus, dyslipidemia, or hypertension).  

Anorectic effect may be a result of sustained activation of anorexigenic neurons in the hypothalamus. Both medications reduce food craving and may be used in patients with obesity and depressed mood.  They also decrease glucose levels, insulin resistance, and lipid levels, and decreases the requirement for glucose lowering drugs in type 2 diabetes mellitus. Treatment should be discontinued if the patient has not lost ≥5% of total body weight after 12 weeks of therapy.

Norepinephrine Agents²  

Example drugs: Mazindol, Phentermine, Phentermine/Topiramate 

Norepinephrine agents enhance catecholamine neurotransmission leading to increased sympathetic activity and reduced appetite. They are not recommended in patients with uncontrolled hypertension or a history of heart disease.  

Phentermine is the most commonly used noradrenergic agent for the treatment of obesity. It does not affect dopamine neurotransmission, hence, there is little potential for abuse. It is recommended for short-term use (<12 weeks) only and is no longer recommended for long-term treatment of obesity.  It reduces total cholesterol and LDL-C. It should be used with caution in patients with anxiety disorders and should closely monitor for changes in behaviors and moods. Severe mental depression may result from abrupt discontinuation after prolonged high-dose intake; hence, it is recommended to gradually withdraw Phentermine therapy.  

Phentermine/Topiramate is associated with greater mean weight loss than the other weight loss preparations. It is approved for the long-term use in the management of obesity. Perform a pregnancy test prior to initiation of therapy and monthly thereafter as fetal toxic effects are linked to Topiramate. 

¹Lorcaserin has been withdrawn from the market after a safety clinical trial demonstrated an increased occurrence of cancer in treated patients.
²Amphetamines 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.  

Peripherally Acting Anti-Obesity Agent  

Orlistat  

Orlistat is the only lipase inhibitor approved for the management of weight loss. It works by inhibiting pancreatic lipase, preventing fat hydrolysis into absorbable fatty acid and thereby decreases fat absorption.  

It is indicated for the treatment of patients with a BMI of ≥30 kg/m², or patients with a BMI of ≥28 kg/m² with associated risk factors (eg type 2 diabetes, hyperlipidemia, and hypertension). It may be used in patients who prioritize modest amount of weight loss and are not bothered by the possibility of gastrointestinal adverse effects.  

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. It has been shown that it reduced blood pressure and glucose levels and improved lipid profile with greater reductions in LDL-C level. 

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. It also inhibits digestion of TG. Current data noted rare cases of severe liver injury with the use of this medication. It can be used for long-term (up to 4 years) weight management.  

Others  

Antidiabetic Medications in Patients with Type 2 Diabetes Mellitus Who are Overweight or Obese  

Antidiabetic medications can result in weight loss (eg GLP-1 receptor agonists, Tirzepatide, Metformin, sodium-glucose linked transporter 2 [SGLT2] inhibitors) or are weight neutral (eg dipeptidyl peptidase-4 [DPP-4] inhibitors and Acarbose). Both GLP-1 receptor agonists and SGLT2 inhibitors reduce the risk of cardiovascular disease events. The optimal medication dose for patients with obesity and type 2 diabetes mellitus would be the dose most available to the patient if the medication has proven benefits for weight reduction, improvement of glycemic control, and cardiovascular disease risk reduction.  

Contraception or active precautions against pregnancy should be advised before and during treatment with antidiabetic medications. One may consider consulting a specialist regarding stopping antidiabetic medications before a planned pregnancy.  

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  

Lisdexamfetamine and Topiramate may be considered as adjunctive therapeutic agents to psychological treatment in overweight or obese patients with binge-eating disorder.  

Dietary Supplements and Herbal Preparations  

There is insufficient evidence to recommend dietary supplements and herbal preparations for the management of obesity. They may contain unpredictable amounts of active ingredients, have unpredictable efficacy, and unknown safety profiles. 

Nonpharmacological

Lifestyle Modification

Diet or Calorie Restriction  

Energy expenditure should be more than total energy intake (caloric deficit). Patients are generally advised to decrease the portion size of food, choose low energy-dense foods and drinks, avoid between-meal snacks, ultra-processed food, sugar-sweetened beverages, or refined carbohydrates, limit sodium and alcohol intake, not to skip breakfast and to avoid nighttime eating, and reduce binge eating. Emphasize the need for a balanced, reduced caloric intake and adherence to dietary therapy for initial weight loss and maintenance. Consumption of low-fat, reduced-calorie diets are important for a successful weight loss for 12 months.  

A calorie reduction of 500-1000 kcal/day from the usual intake should be done to achieve a weight loss of 0.5-1 kg/week (1-2 lb/week). Every 24 kcal/day reduction will result in the long term in approximately 1 kg loss in body weight, or a 15-30% reduction from habitual caloric intake can result in 5-10% weight loss and long-term maintenance. An intake of 1200-1500 kcal/day for most women and 1500-1800 kcal/day for most men can help achieve the treatment goals. Calorie reduction may also be simplified by using a 9-inch plate with half of the plate composed of vegetables and fruits and the other half divided between carbohydrates and protein.  

The amount of fat reduced will depend on each specific country’s national standard. Total fat should be ≤30% of the total calories (trans fat <1%, saturated fat 7-10%, monosaturated fat up to 15% of total calories) and with most fats coming from fish, nuts, and vegetable oils.  

Carbohydrates should comprise 55% of the total calories. Complex carbohydrates from fruits, vegetables, and whole grains are preferred.  

Protein should be ≤15% of the total calories. It should be derived from plant sources or lean animal sources.  

Fiber should get ≥25-35 g/day. It delays gastric emptying causing a feeling of fullness and decreased appetite or hunger. It also helps decrease absorption of fat and cholesterol. It may be obtained from oatmeal, whole wheat bread, rice, beans, citrus fruits, carrots, cauliflower, strawberries, peaches, and apple with skin.  

For vitamins and minerals, the following are the recommended daily intakes:

• Calcium: 1000 mg/day total daily intake which can be derived from diet with or without supplementation (especially for women at risk of osteoporosis)
• Vitamin D: 10-20 mcg/day

Modified Diets  

Clinically meaningful weight loss and improvement in the function of the adipose tissue can be achieved with reduced calorie intake regardless of macronutrients.  

Low-Calorie Diet (LCD) is a food-based approach intended to lower caloric intake by 500 kcal/day from the maintenance requirement regardless of macronutrient composition. The energy content is 800-1200 kcal/day and may require meal replacements to meet caloric and nutritional targets. An average of 8-10% reduction in total body weight was noted over a 6-month period.  

Very Low-Calorie Diet (VLCD) comprised of a caloric intake of <800 kcal/day regardless of macronutrient composition. It uses calorie-controlled, nutritionally balanced, vitamin or mineral-fortified pre-prepared meal replacements utilized as the only nutrient source. It is used for a maximum of 12-16 weeks and monitored by experienced practitioners. It can be extended or used intermittently over longer periods of time at the discretion of the supervising healthcare provider.  

VLCD is indicated in moderately to severely obese patients who are motivated but have failed with conservative methods, or in patients with BMI of 27-30 kg/m² who have medical conditions that might respond to rapid weight loss. Weight regain after rapid weight loss is not faster than gradual weight loss.  

Modified diets can be done by a certified nutritionist or dietitian, and they need to be clinically supervised. Physicians should also consult with nutrition professionals when prescribing a particular weight loss diet, including individualized medical nutrition therapy, that will address the patient’s needs. Patients with obesity-related comorbidities need to work with their physicians to adjust chronic medications.  

Other Dietary Strategies  

The Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean diet are safe and recommended for individuals wanting to lose weight. DASH diet was developed to reduce blood pressure and it emphasizes intake of foods low in sodium, cholesterol, and saturated fats (eg fruits, vegetables, and low-fat dairy foods). The Mediterranean diet requires a high consumption of olive oil, legumes, grains, cereals, fruits, vegetables, and moderate to high consumption of fish and dairy products.  

Intermittent fasting involves fasting and non-fasting periods (eg eating normally for 5 days and then taking in much less energy/calories on the remaining 2 days of the week). A time-restricted feeding is also a form of intermittent fasting wherein food intake is limited to ≤8 hours daily. Fasting-related concerns include mood changes, fatigue, or dizziness. Cardiovascular events can be provoked and aggravated in the elderly. It shows promise for obesity treatment, but further research is needed before using it in the long-term.  

Carbohydrate-limiting diets such as the Atkins and ketogenic diets derive a major portion of the caloric intake from fat sources. Adverse effects include potential increase in LDL cholesterol levels and development of kidney stones.  

Paleo diet, also referred to as the caveman-like diet, is high in protein and low in carbohydrates and usually excludes grains, legumes, and dairy products. It may encourage consumption of large amounts of meat while inadequate intake of other foods which may lead to the development of anemia, osteoporosis, type 2 diabetes mellitus, or hypertension.  

Patients are recommended to seek professional advice before starting any form of diet.  

Physical Activity Interventions  

There is very strong evidence supporting the role of regular physical activity in the prevention and management of risk factors for cardiovascular disease and diabetes mellitus. The benefits of physical activity include reduced weight and fat mass, improved metabolic profile, increased cardiovascular fitness, and improved well-being.  

It can be done in the form of daily unstructured physical activity or structured physical activity featuring aerobic and/or resistance training. Moderate- to vigorous-intensity aerobic exercises (eg swimming, table tennis, 4.3-6.4 kph brisk walking, 16 kph cycling) are recommended for 30-60 minutes, 5 days/week (>150 minutes a week) and could be done as:

• 30 minutes/day for cardiovascular fitness
• At least 150 minutes/week combined with resistance exercise 3 times/week to increase muscle strength
• ≥150 minutes/week to maintain health and prevent diseases
• 150-420 minutes/week to achieve weight loss since a dose-response relationship exists between volume of exercise and the amount of weight loss
• 200-300 minutes/week to maintain weight loss
• A total of 10-60 minutes/day is recommended with gradual increase over time for unfit or inactive individuals

Resistance training using the major muscle groups in single-set exercises may also be advised 2-3 times/week to maintain weight or modestly increase mobility and muscle or fat-free mass. One may consider 5,000-10,000 steps per day as a starting aerobic physical activity in those who are physically inactive or with limited mobility. Appetite is suppressed during and immediately after exercise but increases after an hour. Activity should be tailored to the patient’s age, ability (eg fitness level, physical impairments), and cardiovascular risk. An increase in daily activity and reduction in sedentary time should also be encouraged (eg walking, climbing stairs). 

Obesity_Management

• Enhancement of communication and avoidance of stigmatization
• Psychoeducation which emphasizes on achieving behavioral and psychological goals to improve health, function, and quality of life
• Motivational interviewing and behavioral interventions
  • Motivational interviewing includes patient engagement, focusing on 1 behavior at a time and evoking the patient's internal motivation
  • Behavioral strategies help improve adherence to lifestyle intervention programs
• Psychological interventions which include cognitive behavioral therapy (CBT) and Acceptance and Commitment therapy
  • CBT combined with diet or exercise resulted to a greater weight loss compared to diet or exercise alone
  • Acceptance and Commitment therapies center on value-directed actions and commitment to multicomponent behavioral interventions

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 tailoring, goal setting, self-monitoring, social support, and targeted feedback.  

Comorbidities  

Prevention and treatment of comorbidities are recommended. Regular screening for obesity-related cancers is advised in individuals with obesity.

Surgery

Bariatric and Metabolic Surgery  

Bariatric and metabolic surgery are considered the most effective method to reduce and maintain weight in severely obese patients. They are indicated for severely obese patients who were unable to maintain weight loss by non-surgical methods. They are associated with average weight losses of between 16-35% in up to 8 years depending on the type of surgical procedure. Laparoscopic approach is the first treatment of choice.  

Based on long-term data, surgery has been shown to reduce overall mortality over a 15-year period compared to conservative medical treatment. Surgery improves obesity-related comorbidities and quality of life and decreases cardiovascular mortality and morbidity. Metabolic surgery should be done in high-volume centers with well-informed and experienced multidisciplinary teams. Strict selection criteria should be applied. It may have partial weight regain in up to 35% of patients after 5 years in patients with BMI >35 kg/m².  

The 2022 American Society for Metabolic and Bariatric Surgery (ASMBS), the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO), and the 2024 American Diabetes Association (ADA) stated that metabolic surgery may be considered in the management of patients with BMI ≥30 kg/m² (≥27 kg/m² in Asian Americans) and obesity-related comorbidities (eg type 2 diabetes mellitus, hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, asthma, fatty liver, chronic kidney disease, gastroesophageal reflux disease, polycystic ovarian syndrome, and bone and joint diseases).  

The second Diabetes Surgery Summit (DSS-II) recommends metabolic surgery for the treatment of type 2 diabetes mellitus Asian patients with a BMI ≥37.5 kg/m² and a BMI 32.5-37.4 kg/m² when optimal lifestyle and medical treatment are inadequate to control hyperglycemia. It also considers metabolic surgery for patients with BMI 32.5-37.4 kg/m² with adequate glycemic control and BMI 27.5-32.4 kg/m² with poor glycemic control despite optimal lifestyle and medical treatment (including injectable medications and Insulin). 

The International Federation for the Surgery of Obesity and Metabolic Disorders - Asia Pacific Chapter (IFSO-APC) consensus statements in 2011 recommend bariatric surgery in the following Asian patients with:

• BMI ≥35 kg/m² with or without comorbidities 
• BMI ≥30 kg/m² inadequately controlled by lifestyle changes or medical therapy for the treatment of type 2 diabetes mellitus or metabolic syndrome
• BMI ≥27.5 kg/m² as non-primary treatment alternative for inadequately controlled type 2 diabetes mellitus or metabolic syndrome

The contraindications to bariatric or metabolic surgery are current alcohol or substance abuse, unstable psychological conditions, esophageal dysmotility, inflammatory bowel disease, chronic pancreatitis, bile duct pathology, portal hypertension, active malignancy, regular use of non-steroidal anti-inflammatory drugs (NSAIDs), and history of gastric cancer. Relative contraindication includes inability to comply with postoperative nutritional changes or follow-ups.  

The commonly performed bariatric surgery procedures in Asia include sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), adjustable gastric band (AGB), and biliopancreatic diversion with duodenal switch (BPD-DS). Endoscopic bariatric procedures include intragastric balloon and endoscopic sleeve gastroplasty (ESG). ESG results in about 15-20% weight loss at 12-24 months when combined with lifestyle modification.  

Obesity_Surgery