Obesity

Description
  • Obesity has become common in Canada-approximately 59% of the population is overweight and 23% are obese.

  • The obesity rate in children has risen significantly over the last 10 years.

  • Current evidence supports the view that obesity is a disease, although it is also a societal issue.

  • Being obese increases the risk of many chronic disease and health conditions such as: coronary heart disease, stroke, hypertension, insulin resistance, type 2 diabetes, dyslipidemia, gallbladder and liver disease, osteoarthritis, and respiratory diseases.

  • Colon cancer and hormonally related cancers such as prostate, endometrial and breast cancer, have been associated with obesity.

  • For more information, go to:

Signs and Symptoms
  • The most widely accepted classifications of obesity are from the World Health Organization (WHO) and are based on body mass index (BMI). The WHO designations are as follows:
    • Grade 1 overweight: BMI of 25-29.9 kg/m2
    • Grade 2 overweight (commonly called obesity): BMI of 30-39.9 kg/m2
    • Grade 3 overweight (commonly called severe or morbid obesity): BMI ≥40 kg/m2
  • BMI is a measure of body fat based on height and weight that applies to adult men and women.  The formula for BMI is weight in kilograms divided by height in meters squared.
  • BMI calculators are available at:
  • Visceral adiposity, as determined by waist measurement, increases morbidity associated with obesity.  Waist circumference of > 88 cm or 35 inches in women and > 102 cm or 40 inches in men is indicative of increased cardiometabolic risk.
  • All cause, metabolic, cancer and cardiovascular morbidity begin to rise when BMIs are >25 kg/m2.
Differential Assessments

Before proceeding to treatment, consider the following conditions which can cause or contribute to obesity:

  • Elevated BMIs associated with increased muscle mass rather than obesity, as seen in body builders and athletes
  • Medication-induced weight gain, for example: insulin, antipsychotics, corticosteroids
  • Anxiey, depression - may alter eating habits
  • Type 2 diabetes mellitus
  • Excess fluid retention
  • Endocrine diseases such as hypothyroidism, polycystic ovarian syndrome, Cushing's disease, antipsychotics syndrome, central hypothyroidism and hypothalamic disorders – may cause or worsen obesity
  • Insulinoma - tumor of the pancreas that secretes insulin.  Sudden weight gain may occur
When to Refer
  • BMI >35 with comorbidities or BMI > 40 – patient may be a candidate for bariatric surgery
  • Less than 5% of weight loss after adequate trial of orlistat (3 months recommended)
  • Intolerance to orlistat and insufficient weight loss with lifestyle modification
  • Suboptimal treatment of any differential diagnosis condition
  • Patients should be referred to a dietitian if they ask for or require advice on nutrition and / or diet programs. Access information for Saskatchewan registered dietitians is available at https://www.saskdietitians.org/about-dietetics/how-can-i-access-an-rd/
Treatment

Non-pharmacologic treatment:                                                                                                                                

  • Adults: treatment of obesity should start with lifestyle modification: diet, exercise and behaviour modification.  This requires a highly motivated patient and, preferably, a team of health professionals. 
    • Diet: Reduce energy intake by 500-1000 kcal/day.  Many diets are effective.  Consultation with a dietitian is required.
    • Exercise: Start with 30 minutes of moderate intensity exercise 3-5 times/week and increase to 60 minutes or more on most days.  Add endurance exercise training. Always consult with physician before starting exercise regimen.
    • Behaviour modification: Cognitive behavior therapy, group weight-loss programs, on-site or telephone counseling.
    • Weight loss goals should be realistic and well-defined. 
  • Children: the goal is not to cause weight loss, but to reduce the rate of weight gain to fit normal growth curves.
    • Modify diet
    • Increase exercise
    • Decrease time spent in sedentary activities eg watching TV, playing computer games
    • Behaviour modification
  • Bariatric surgery should be considered for patients with BMIs of 35 kg/mand comorbidity or BMI over 40 kg/m2 in addition to lifestyle modification

 Over-The Counter medications:

  • There is insufficient evidence to recommend for or against the use of herbal remedies, dietary supplements or homeopathy for weight management in the obese person
  • Many OTC and herbal products are marketed for weight loss.  Many contain vitamins and may not be harmful.  Others may have serious deleterious effects.  The pharmacist should always check ingredients for safety, suitability, drug interactions, contraindications and duplication of therapy
  • Fibre products might be useful to give feeling of satiety although the commonly used agents, guar gum and psyllium, do not produce weight loss

Prescription Medications: 

  • In patients with comorbid conditions, medications that promote weight loss or are weight neutral are preferred and should replace medications causing weight gain if appropriate. 
  • Preferred medications for the obese patient:

Class of Medication

Specific Medication

Reason for preference

Antidiabetic agents

Metformin

GLP-1 analogs: exenatide, liraglutide

SGLT-2 inhibitors: canaglifozin, dapagliflozin, empaglifozin

 

Promote weight loss

DPP-4 inhibitors: alogliptin, linagliptin, saxagliptin

α-glucosidase inhibitor: acarbose

Weight neutral

Basal insulin

Less weight gain than insulin alone or insulin with sulfonylureas

Antipsychotics

Ziprasidone

Promotes weight loss

Aripiprazole

Weight neutral

Antiepileptic agents

Topiramate

Zonisamide

Promote weight loss

Lamotrigine

Levetiracetam

Phenytoin

Weight neutral

Antihypertensives in

T2DM

ACE inhibitor

Angiotensin receptor blocker

Calcium channel blocker

Preferred over beta-

blockers

Contraceptives

Hormonal contraceptives

Low dose - less likely to cause weight gain

Weighf gain reported with injectable medroxyprogesterone acetate

Antidepressants

Bupropion

Fluoxetine

Weight loss reported

Anti-inflammatories

NSAIDs

DMARDs

Recommended over corticosteroids which often cause weight gain

 

  • In patients with BMI ≥ 27 kg/m2  plus risk factors or BMI ≥ 30 kg/m2 , the use of approved weight loss medications is suggested if unsatisfactory weight loss after a trial of lifestyle changes for at least six months.
  • There are three prescription agents with the indication for weight loss in Canada:

1. Xenical™ (orlistat)

  • Indications:
    • Obesity management including weight loss and weight maintenance
    • Reducing the risk of weight regain in obese patients after prior weight loss
  • MOA
    • GI lipase inhibitor which reduces dietary fat digestion and absorption
    • Averages a 6.5 to 7.5 lb/year weight loss over and above weight loss associated with diet and exercise
  • Contraindications:
    • Malabsorption syndromes, cholestasis
    • Caution in patients with pre-existing disease of the bowel or rectum
  • Dosage:
    • 120mg po tid (during or up to 1 hour after each meal).
      • Omit dose if meal is skipped or meal contains no fat.
      • Orlistat should be taken with a mildly reduced-calorie diet that contains no more than 30% of calories from fat.  If greater percentage of calories are from fat, there is greater chance of GI side effects.
  • Side effects:
    • GI side effects include:  flatus with discharge (40%), oily spotting (33%), fecal urgency (30%), and fecal incontinence (12%).  More likely to occur when orlistat is taken with high fat meals.
    • Other side effects: irregular menstrual periods, headache and anxiety.
    • Orlistat may reduce absorption of fat-soluble vitamins (A,D,E,K) and beta-carotene - supplementation may be required.
      • Separate doses – take at least 2 hours before or after administration of orlistat.
    • Patients with a history of oxalate kidney stones may develop increased levels of oxalate in their urine, which may increase the risk of kidney stones
    • Severe liver injury with hepatocellular necrosis or acute hepatic failure have been reported in postmarketing reports.  Monitor liver function tests if hepatic dysfunction is suspected
    • Monitor glycemic control in diabetics as weight decreases
  • Drug interactions:
    • Decreased vitamin K absorption may increase anticoagulation with warfarin.  Increased INR monitoring is warranted.
    • Orlistat may decrease the absorption of cyclosporine,  levothyroxine, anti-epileptic drugs and antiretrovals – separate dosing times by 3-4 hours and monitor for reduced efficacy.
  • Not recommended in pregnancy and lactation
    • Weight loss during pregnancy is not recommended.
    • Unlikely to be excreted in breast milk so would not affect the infant directly but could cause vitamin deficiencies in the mother that might adversely affect the infant.
  • Prescribing for children < 18 years of age is out of pharmacists' prescribing scope.

2. Liraglutide (Not currently in scope for pharmacist prescribing)

  • Doses of 2.4 mg and 3 mg injected SC once daily were found to be significantly more effective than orlistat (approximately 8 kg weight loss through 2 years of therapy) for the management of obesity in nondiabetic patients.
  • Expensive - > $400/month.

3. Bupropion / naltrexone (Not currently in scope for pharmacist prescribing)

  • Reduces appetite, decreases cravings
  • Target dose of two 90/8 extended release tablets twice daily reduces weight by approximately 5 kg over 1 year
  • Expensive -  $300/month.

4. Medications used off-label (Not currently in scope for pharmacist prescribing)

  • Methylphenidate - several anecdotal reports indicate variable success for weight loss.
  • Topiramate - has been associated with weight loss on an average of 5-7% of initial weight. The amount of weight loss appears to be greater with higher baseline weights.
  • Metformin - improves insulin resistance. It's use is associated with weight neutrality or mild weight loss.
  • Bupropion - associated with minimal to moderate weight loss in obese patients.
General Advice / Monitoring

General Advice

  • Orlistat is an adjunct to lifestyle measures for weight loss. Diet, exercise and behavior modification should continue to be the major focus of the weight loss program.
  • Take one capsule (120 mg) during or just following each main meal (breakfast, lunch and dinner). Swallow the capsule whole along with some water. Take the capsule no later than 1 hour after the meal is eaten.
  • Combine with a mildly reduced calorie diet - average 20% decrease in daily calories, and no more than 30% of calories from fat. Intake of fat, carbohydrate and protein should be distributed over three main meals. (Recommend consulting a dietitian.)
  • Do not take a capsule if a main meal is missed or if a meal contains no fat.
  • Consider taking a multivitamin containing the fat-soluble vitamins once daily at least 2 hours after or before orlistat dose.
  • GI side effects are usually mild and short-lived.
    • More likely to be troublesome if large amounts of fatty foods are eaten.
  • Serious side effects are rare.  If any the following occur, contact your pharmacist or doctor:
    • Persistent nausea and vomiting
    • Severe abdominal or back pain
    • Blood in urine or stool
    • Itching, yellowing of the skin, dark urine, light colored stools
  • If you have diabetes, watch for symptoms of hypoglycemia as weight loss occurs.

Assess Benefit

  • Benefit is defined as weight loss of 5% or more of body weight at 3 months.
  • If beneficial, treatment should be continued and reassessed in 1 year.  FDA has approved use of orlistat for up to 2 years and studies have shown safety in up to 4 years of use.
  • If ineffective, (weight loss less than 5% at 3 months) or if there are safety or tolerability issues at any time, it is recommended that orlistat be discontinued. 

Assess for Adverse Effects

  • Follow-up with patient 2 weeks after initiation of orlistat therapy to determine tolerability.
  • Ask about GI side effects:  flatulence, fatty/oily/loose stool, increased defecation and fecal incontinence.  If a problem, recommend reducing fat content of meals and increasing fibre intake (e.g., psyllium).
  • Other side effects: irregular menstrual periods, headache and anxiety.
  • Monitor for hepatic impairment. Symptoms include: jaundice, pruritis, dark urine, anorexia, light colored stools and abdominal pain.
  • Monitor for development of kidney stones.
  • If diabetic, monitor for signs of hypoglycemia.
  • Poorly monitored weight loss and weight cycling can lead to complications such as:
    • Cardiac arrhythmias
    • Electrolyte imbalances - Hypokalemia is the most important of these
    • Hyperuricemia
    • Depression and the development of eating disorders (particularly binge-eating disorders)
    • Gallstones
Products
Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in RxTx - CPS from CPhA, RxTx (Internet), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).
This information should be routinely consulted before prescribing.

Drug

Dosage

Orlistat

120mg TID
Prescribing and Billing Details
  • Fee pseudoDIN 00951325; maximum of 1 claim per year
  • May prescribe a 1 year supply
  • Only products with an official indication from Health Canada for obesity and/or recommended by reputable and reliable guidelines are considered for these guidelines. Only the active ingredients in the "products" section are approved for pharmacist prescribing.
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Finally, a roadmap for managing obesity in primary care. Canadian Obesity Network.  Available at http://www.obesitynetwork.ca/5As.
  2. Hamdi O. Obesity Treatment and Management. In: Medscape online database. Available at http://emedicine.medscape.com/article/123702-treatment. (Free access with registration)
  3. Lau D, Douketis J, Morrison Katherine M.  2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ 2007;176, No. 8. Available at http://www.cmaj.ca/content/suppl/2007/09/04/176.8.S1.DC1/obesity-lau-onlineNEW.pdf.
  4. Jensen MD, et al. 2013 AHA/ACC/TOS Obesity Guideline 2013 AHA/ACC/TOS. Available at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/01.cir.0000437739.71477.ee/-/DC1.
  5. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline 2015. J Clin Endocrinol Metab 2015; 100:342–362. Available at http://press.endocrine.org/doi/pdf/10.1210/jc.2014-3415.
  6. Recommendations for prevention of weight gain and use of behavioural and pharmacologic interventions to manage overweight and obesity in adults in primary care - Canadian Task Force on Preventive Health Care 2015. CMAJ February 17, 2015;187:184-195. Available at http://www.cmaj.ca/content/187/3/184.full.pdf+html.
  7. Bray G. Obesity in adults: Overview of management, In: UpToDate online database. Available at www.uptodate.com (by subscription).
  8. Orlistat. In: Lexicomp Online®, Lexi-Drugs® , Hudson, Ohio: Lexi-Comp, Inc.; Accessed March 7, 2016 (by subscription)
Written by medSask
Posted May 2018; Updated Oct 2018