Resident Editor: Joseph R. Cartwright, M.D., M.Ed.

Faculty Editor: Michelle Guy, M.D.

Bottom Line:

• Obesity is increasingly prevalent chronic disease that must be directly addressed.
• Even modest weight loss (5-10%) improves both metabolic (e.g. DM2) and fat mass disease (e.g. CHF, OSA, GERD, OA).
• Diet, exercise, and behavior modification form the foundation of any weight loss program.
• Since 2012, four weight loss medications (lorcaserin, naltrexone-bupropion, liraglutide, and phentermine-topiramate) have been approved by the FDA for long-term use for obesity, and early outcomes research shows significant and durable weight loss.
• Bariatric procedures are the most effective treatment, and interested patients with BMI>40 or BMI >35 with obesity-related comorbid diseases (e.g. DM2) should be referred for consultation with a surgical program.

Background

• Obesity is a chronic disease.
• Obesity prevalence is increasing: 40% in US adults and 18.5% in youths (2015-2016).
• Obesity is associated with increased risk of cardiovascular disease, metabolic disorders and greater than 200 other comorbidities.
• Even modest weight loss (5-10%) improves both metabolic and fat mass disease.
• There is no one-size-fits all approach to weight loss.
• Effective interventions are multimodal and combine the following:
  • nutritional intervention
  • physical activity
  • behavioral strategies
  • pharmacotherapy (if appropriate)
  • bariatric procedures (if appropriate)
• Since 2012, multiple new anti-obesity drugs have been approved by the FDA for long-term use for obesity, and the early outcomes research shows that these medications help patients achieve significant and durable weight loss.
• Unfortunately, there are many barriers to optimal care for patients with obesity, including discrimination and stigma, inadequate provider education, and insurance coverage challenges.
  • Less than 25% of patients attending primary care visits have their BMI measured.
  • Less than 20% of patients with obesity have a documented diagnosis.
  • Among 41 surveyed internal medicine primary care clinicians (NPs and MDs) at Richard Fine People’s Clinic at ZSFGH, there were a number of perceived barriers to optimal care for patient with obesity.
    • Only 24% (10) of providers felt “very comfortable” discussing obesity/weight loss in some way during a patient encounter.
    • 59% (n=24) felt “very uncomfortable” or “uncomfortable” prescribing medications for weight loss.

Barrier to Prescribing Weight Loss Medications (among ZSFGH Primary Care Clinicians)
Barrier	Percentage (n) of providers who answered “moderate barrier” or “strong barrier”
Provider knowledge of medications	82% (32)
Insurance coverage issues	75% (30)
Provider attitude (e.g. preference for non-pharmacologic methods)	66% (27)
Clinic Infrastructure	51% (21)
Contraindications e.g. renal/hepatic impairment	39% (16)
Patient attitudes e.g. fear, stigma, misunderstanding	27% (11)

Sequelae

• Obesity leads to comorbid disease via several main pathways.
  • Metabolic Disease / Sick Fat Disease (“Adiposopathy”) secondary to endocrinological and immunological responses:
    • hyperglycemia/diabetes mellitus
    • hypertension
    • dyslipidemia
    • fatty liver disease
    • polycystic ovarian syndrome
    • other metabolic diseases
  • Fat Mass Disease secondary to pathologic physical forces:
    • CARDIOVASCULAR:
      • CHF or cor pulmonale
      • varicose veins
      • thromboembolic disease (DVT/PE/CVA/MI)
      • HTN
    • PULMONARY:
      • dyspnea
      • OSA
      • OHS
      • asthma
  • NEUROLOGICAL:
    • intracranial hypertension (aka pseudotumor cerebri)
    • stroke
    • nerve entrapments (e.g. meralgia paresthetica, carpal tunnel syndrome)
  • MUSCULOSKELETAL:
    • Immobility (e.g. fatigue/deconditioning)
    • Stress of weight-bearing joints (e.g. osteoarthritis)
    • Low back pain
    • Myalgias
    • Altered center of gravity
    • Impaired balance
  • GASTROINTESTINAL:
    • GERD
    • Hernias
  • DERMATOLOGICAL:
    • striae (e.g. skin stretch marks)
    • stasis pigmentation
    • venous statis ulcers
    • cellulitis
    • skin tags
    • intertrigo
    • carbuncles
  • Psychosocial sequelae:
    • depression
    • hopelessness
    • low self-esteem
    • low lidibo
    • decreased productivity
  • Bias (from society, family, workplace, providers, insurance companies, etc)
    • bias → self-stigmatization → increased mental stress → maladaptive behaviors, adiposopathic stress responses and metabolic disease

Evaluation

• USPSTF recommendation: screen all patients for obesity by measuring their body mass index (BMI). (Note: different BMI cut-offs may be more appropriate for patients of different gender, race, ethnicity, or menopausal status).
• Initial assessment: gather information on dietary intake, activity level, possible secondary causes of obesity (including hypothyroidism, Cushing syndrome and medication effects), as well as identification of existing comorbidities.

CLASSIFICATION	BMI
Underweight	<18.5 kg/m2
Normal Weight	18.5 – 24.9 kg/m2
Overweight	25 – 29.9 kg/m2
Obesity (Class 1)	30 – 34.9 kg/m2
Obesity (Class 2)	35 – 39.9 kg/m2
Extreme Obesity (Class 3)	> 40 kg/m2

• Review necessity of medications that may promote weight gain:
  • glucocorticoids (prednisone)
  • second-generation antipsychotics (risperidone, olanzapine, clozapine, quetiapine)
  • antiepileptics (gabapentin, carbamazepine, valproic acid)
  • antidepressants (any SSRIs or TCAs)
  • lithium
  • beta-blockers (propranolol, atenolol, metoprolol)
  • calcium-channel blockers (dihydropyridines subclass e.g. amlodipine)
  • certain diabetes medications (insulin, thiazolidinediones [pioglitazone], sulfonylureas)
  • alpha-agonists (prazosin, terazosin)
  • chemotherapies (tamoxifen, methotrexate, anastrazole)
  • hypnotics (diphenhydramine)
• Waist circumference: Consider measuring waist circumference to determine central adiposity. This may be especially helpful in patients who do not meet BMI criteria for obesity, who in whom you suspect metabolic disease.
  • Technique: measure over iliac crest
  • High risk if >35 inches (88cm) for women or >40 inches (102cm) for men.
• Laboratory evaluation: Screen for diabetes (fasting glucose or Hemoglobin A1c), dyslipidemia (fasting lipids), thyroid dysfunction (TSH), and fatty liver disease (liver function tests).

Treatment

• There is no one-size-fits-all approach to weight loss.
• Modest weight loss (reduction in 5-10%) reduces burden of comorbid medical conditions.
• Weight loss is best achieved with a combination of dietary therapy, physical activity, behavioral modifications, and, where appropriate, medications or bariatric surgery.

Dietary Therapy: Decreased daily caloric intake that results in an energy deficit can lead to weight loss. Individuals should be referred to a nutritionist for guidance and creation of a personalized treatment plan. Some special diets are described below.

• Very low calorie diet (VLCD, <800 kcal/day).
  • Administered under close medical supervision among obese individuals with major health risks.
  • Duration: typically 1-3 months.
• Low calorie diet (LCD, <1200 kcals/day).
  • Goal: achieve approximately 500 kcal energy deficit each day (a deficit of 3500 kcal equals one pound lost).
  • Duration: typically 1-3 months. 
• Meal replacement programs (e.g. Weight Watchers®, Jenny Craig®, Nutrisystem®):
  • Reduces portion sizes and makes calorie counting easier.
  • Mixed results in achieving sustainable weight loss.
  • Integration of such programs into a primary care or weight management practice can improve the degree and durability of weight loss achieved.
  • Duration: variable.
• General Principles of Diet Programs:
  • Durability of weight loss after VLCD/LCD can be enhanced by anti-obesity drugs, subsequent diet plan, and exercise after the initial intense diet (which is usually carried out over 1-3 months).
  • Cognitive behavioral therapy as an adjunct to dietary changes has been shown to improve weight loss (compared to dietary changes alone)
  • Calorie-controlled diets demonstrate more sustainable weight loss than low carbohydrate or low fat diets. 

Physical Activity: Physical activity can lead to weight loss by increasing energy expenditure. Data show that physical activity is especially important for maintaining weight loss. Patients can begin by increasing the frequency and/or duration of their current activities, and then increasing the intensity of these activities over time.

• Consider exercise stress testing in high-risk (age >50, multiple cardiac risk factors) patients before an intense exercise regime is begun.
• 30 minutes or more of continuous aerobic exercise at least 5 times a week is recommended (150-250 minutes/week) for weight maintenance. 
• >250 minutes/week should be a goal for long-term weight loss strategies. 
• Resistance training should also be incorporated to preserve muscle mass and sustain an individual’s resting metabolic rate. 

Behavioral Modification: Behavior modification strategies are designed to improve eating habits and increase physical activity as a means of achieving sustainable weight loss goals. Simple strategies of planning and record keeping should be encouraged. More sophisticated behavioral therapy requires an individualized plan developed with the patient by a trained professional in a personal or group setting and close long-term follow-up.  Smart-phone applications and online resources are becoming more popular; however, very few have been studied in randomized control trials (see resources below). 

Pharmacotherapy (e.g. Anti-Obesity Drugs): Consider in patients with BMI > 30 or BMI > 27 with comorbidities. A number of new medications have been approved by the FDA since 2012. While long-term durability of medication-assisted weight loss is an actively researched area at this time, the early results appear promising. The side effect profile and dual indications (e.g. liraglutide for diabetes) should be considered. Medication must produce at least 5% weight loss after 12-16 weeks to be deemed effective.  If effective, consider continuing long-term. 

• FDA-Approved for Long-Term Use:

FDA-Approved Weight Loss Medications (for Long-Term Use)
Medication	Mechanism	Side Effects (and Contraindications)	Mean Weight Loss in Excess of Placebo at 1 year (JAMA 2016)	Pearls	Dosing
Orlistat (Xenical®, Alli®)	Inhibits pancreatic lipase, reducing fat absorption	Side effects: -oily, malodorous stools -fecal incontinence -cholelithiasis -kidney stones (oxalate) -liver injury (rare) -decreased fat-soluble vitamin absorption (A, D, E, K)   Absolute contraindications: none Relative contraindications: none Pregnancy Category: X (do not use)	2.63 kg	Available OTC (Alli®).   Rx with multivitamin.	60mg-120mg PO TID with fat-containing meals.   Take other meds >1h before or after orlistat.
lorcaserin (Belviq®)	selective agonist of serotonin (5HT2c) receptor, regulating appetite	Side effects: -serotonin syndrome -headache -fatigue -cough -memory disturbance -hypoglycemia in type II diabetics   Absolute contraindications: none Relative contraindications: co-administration of serotonergic agents (safety not established) Pregnancy Category: X (do not use)	3.25 kg	Difficult to get covered by most insurances.	10mg PO BID   Caution if CrCl 30-50   Avoid if CrCl <30
naltrexone- bupropion (Contrave®)	opioid antagonist / dopamine+norepinephrine reuptake inhibitor	Side effects: -headache -constipation -insomnia -suicidality (rare)   Absolute contraindications: opioid use, seizure disorder, anorexia/bulimia Relative contraindications: uncontrolled HTN Pregnancy Category: X (do not use)	4.95 kg		2 tabs PO BID   Start 1 tab daily to 4 tabs daily slowly over 4 weeks.   Caution in CKD1-2. Max 1 tab BID in CKD 3-4. Avoid in CKD5.   Max 1 tab qAM in hepatic impairment.
liraglutide (Saxenda®)	glucagon-like peptide-1 (GLP-1) receptor agonist; increases satiety and decreases gastric emptying	Side effects: -nausea and vomiting (dose dependent) -diarrhea -hypoglycemia -hyperlipasemia   Absolute contraindications: personal or family history of MEN2 syndrome or medullary thyroid cancer Relative contraindications: none Pregnancy Category: “not recommended”	5.24 kg	Excellent first choice for diabetics.   May require trial of metformin before insurance authorization.   Start at  0.6mg SQ daily and uptitrate weekly  to max of 3.0mg daily.	3.0mg SQ daily   Start at 0.6mg and uptitrate by 0.6mg weekly.
phentermine- topiramate (Qsymia®)	norepinephrine-release combined with  GABA-receptor modulation	Side effects: -dry mouth -paresthesia -tachycardia -insomnia -increased creatinine   Absolute contraindications: glaucoma, MAOi use, pregnancy Relative contraindications: CKD (dose adjust), HTN, drug abuse hx, alcohol abuse, nephrolithiasis Pregnancy Category: X (do not use)	8.8 kg	Requires controlled rx.   May be more affordable to patient if rx’d as two medications instead of the combination.	7.5mg/46mg - 15mg/92mg PO qAM   Start at 3.25mg/23mg x 14 days.   Max dose 7.5mg/46mg if CrCl <50 or Child-Pugh B.   Undefined in HD or Child-Pugh C.

• FDA-Approved for Short-Term Use (up to 12 months):
  • Phentermine (Adipex®, Suprenza™): A sympathomimetic drug that works as an anorexiant and is approved by the FDA for short-term use as monotherapy (up to 12 months; Schedule IV drug). Can cause hypertension, tachycardia, and has potential for dependence and abuse.
  • Diethylpropion (Tenuate®), Phendimetrazine (Bontril®), Benzphetamine (Didrex®): All sympathomimetic drugs that work as anorexiants, but are not commonly used.  They are approved by the FDA for short-term use (typically <12 weeks; Schedule III or IV drug). Side effects include hypertension, tachycardia, GI disturbances, insomnia, and the potential for dependence and abuse.
• Adjuvant Medications for Weight Loss:
  • Metformin: first-line oral antidiabetic drug that increases insulin sensitivity while decreasing hepatic glucose production and intestinal glucose absorption. Weight loss of 2.8kg at 1 year. A trial of this agent may be required before insurances will approve the more efficacious liraglutide.

Bariatric Surgery: Bariatric surgery is far and away the most effective treatment for obesity, and recent literature demonstrates that these procedures yield substantial weight loss that endures at 10 years post-operatively.  Eligible patients include those with a BMI≥40 or a BMI ≥35 kg/m² plus obesity-related comorbidities (e.g. DM, OSA). Consider referral for eligible and interested patients who have failed diet and exercise, or for individuals with BMI ≥35 kg/m² who have obesity-related comorbidities.

• Sleeve Gastrectomy (SG)
  • Restriction/Resection and Metabolic
  • Ideal Candidate:
    • BMI 35‐55 kg/m2
    • Needs to lose 80‐150 lbs
  • Benefits:
    • Excess Weight Loss 70‐90%
    • 1‐2 hour procedure
    • Recovery ranges from days to weeks
    • Patients report early and lasting fullness
    • Intestines stay intact—No malabsorption
    • May cure diabetes
  • Considerations/Risks
    • Removal of a portion of the stomach is permanent
    • The remaining pouch may expand over time
• Roux-en-Y Gastric Bypass (aka “Bypass” or RYGB or RNY)
  • Restrictive/Malabsorptive & Metabolic
  • Most common procedure performed
  • Ideal Candidate:
    • BMI 35-55 kg/m2
    • Needs to lose 100-150+ lbs
    • May have severe or prolonged medical conditions
  • Benefits
    • Excess Weight Loss 70-90%
    • 2 hour procedure
    • Recovery of days to weeks
    • Very effective for curing diabetes
    • Approximately 100-200 calories per day lost through malabsorption
    • Procedure is reversible
  • Considerations/Risks
    • Greater risk for vitamin deficiencies
    • Dumping syndrome
    • Smoking, EtOH, NSAIDS use may lead to ulcers
• Biliopancreatic Diversion with or without Duodenal Switch (BPD/DS)
  • Restriction, Resection, Malabsorptive & Metabolic
  • Ideal Candidate
    • BMI > 60 kg/m2
    • Poorly controlled diabetic
  • Benefits Has the highest cure rate for diabetes
    • Excess Weight Loss  80‐90%
    • 3‐4 hour procedure
    • 200‐400 cal lost from malabsorption
  • Considerations/Risks
    • Not offered by most surgeons (including UCSF)
    • Stomach removal is permanent but bypass may be reversed
    • Highest risk for vitamin and protein deficiencies, diarrhea and intestinal blockages
• General Complications of Bariatric Surgery:
  • Peri-operative mortality rate: varies by procedure but ranges from 0.1% in some studies to up to 2% in older, sicker patients. 
  • Complications: incisional hernia, nutritional deficiency, pulmonary embolism, obstruction, port/tubing malfunction, pouch/esophageal dilation, esophagitis, and infection. 
  • Risk of vitamin deficiency. Typically require multivitamin, vitamin B12, iron, calcium and vitamin D.  PPI should be considered due to high-acid production post-procedure.
• Obesity Treatment Devices (FDA-Approved):
  • Lap-Band Adjustable Gastric Banding System: band restricts entry of food into stomach. This procedure is falling out of favor as a the sole intervention for weight loss as of 2018 due to low efficacy and high rate of device removal.
  • Maestro Rechargeable System: electrical stimulator placed in abdomen to block nerve activity between brain and stomach.
  • Gastric Balloon Systems (ReShape, ORBERA, Obalon): inflatable balloons take up space.
  • Gastric Emptying Systems (AspireAssist): percutaneous tube used to drain food after eating.

When to Refer

• ...To a Medical Weight Management Program
  • It is appropriate to refer any patient with obesity (BMI>30) to a multidisciplinary weight management program.
  • Ideally, many pillars of an effective, multimodal weight management program can be conducted within a patient’s primary care home. However, should any of the following interventions be unattainable or suboptimal in the primary care practice, a referral to a medical weight management program is recommended:
    • nutrition education services
    • exercise counseling
    • behavioral therapy
    • weight loss pharmacotherapy prescription
    • progress monitoring
• ...To a Surgical Weight Management Program (“Bariatrics”)
  • It is appropropriate to refer interested patients with BMI>=40 or BMI>=35 with obesity-related comorbidities (e.g. diabetes) to a surgical weight management program as these patients meet the baseline eligibility requirements for bariatric surgery.
  • Bariatric surgeons typically ask that patients have attempted 3-6 months of medically supervised weight loss efforts prior to surgery. Documentation of these efforts by the primary care provider is sufficient and there is typically no absolute requirement for pre-surgical weight loss.  
  • Most insurances, including Medi-Cal, cover bariatrics for eligible patients. (note: Healthy SF is not technically insurance, and unfortunately does not cover bariatrics at this time.)

Additional weight management resources

• UCSF Weight Management Program: (415) 353-2105; offers spectrum of services from behavioral therapy to supervised VLCD: see referral guidelines below.
• ZSFG Weight Management Clinic, Bldg 90, 2^nd Floor; offers nutrition and behavioral education, weight loss pharmacotherapy, and assistance with referral to UCSF Bariatrics Surgery program. Director: Sarah Kim, MD (Endocrinologist).
• SFVAMC Move! Strength and Wellness Program; designed by the VA National Center for Health Promotion and Disease Prevention (NCP), this program offers physical fitness activities, nutritional info, and behavioral health coaching for veterans. HPDP Manager Sandra Smeeding, PhD, CNS, FNP, at (415) 221-4810, ext. 2-5269.
• Obesity Medicine Association: http://obesitymedicine.org. (the 2018 Obesity Algorithm is downloadable here).
• Overeaters Anonymous: http://www.oa.org, (505) 891-2664
• The Obesity Prevention Source @ Harvard MS (great links to all obesity resources). http://www.hsph.harvard.edu/obesity-prevention-source/
• Take Off Pounds Sensibly (TOPS): http://www.tops.org, (800) 932-8677
• Weight-control Information Network (NIH): http://win.niddk.nih.gov/
• Weight Watchers: www.weightwatchers.com,  (800) 562-6962

Table: Referral Guidelines for UCSF Weight Management Program

Insurance	Required Diagnosis	Weight Management Program	Nutritionist	Behavioral Counseling
HILL PHYSICIAN MEDICAL GROUP INSURANCE	“Obesity” or “Overweight” with medical co-morbidities listed	Select “Ambulatory Referral to Weight Management” in APeX; patients will see MD, nutritionist and participate in weekly evening group.	Choose “Ambulatory Referral to Nutrition Services” in APeX, add the name David Besio in comments.  All Hill patients get 10 nutrition visits/year with a medical diagnosis (any BMI).	May include behavioral counseling depending on insurance.
MEDICARE	“Abnormal weight gain” or any weight-related disease.  If DM or CKD listed, Nutrition is also covered.	Choose “Ambulatory Referral to Weight Management” in APeX.	Choose “Ambulatory Referral to Nutrition Services” in APeX, add the name David Besio in comments.	May include behavioral counseling depending on insurance.
MEDI-CAL	“Obesity” or “Abnormal weight gain.”	Choose “Ambulatory Referral to Weight Management” in Apex Patients will see MD and nutritionist. Will need to pay out of pocket to engage in weekly evening group.	Included, follow steps above.	Not a covered service.

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