Obesity

Obesity is a chronic, progressive, and relapsing disease characterized by the accumulation of excess or abnormal body fat (adiposity) that impairs health.^[1] The World Obesity Federation and the Canadian Medical Association both classify obesity as a chronic medical disease, not a lifestyle choice or a failure of willpower — this reframing matters clinically because it is the basis for treating obesity pharmacotherapy the way any other chronic disease medication is treated: started when indicated, titrated to effect, and continued long-term rather than stopped once a weight target is reached. Body mass index (BMI) remains the most widely used screening measure, but weight distribution and organ-level (ectopic) fat matter as much as total adiposity, and BMI alone systematically under- or overestimates health risk in several populations — young adults who have not finished growing, very muscular adults, adults over 65, and people of Asian, Black, or Indigenous ancestry, for whom cardiometabolic risk begins at a lower absolute BMI.^[2] This chapter focuses on pharmacotherapy: incretin-based GLP-1 and dual GIP/GLP-1 receptor agonists are now the preferred pharmacologic option for most candidates, with older agents (orlistat, naltrexone-bupropion, phentermine) reserved for specific situations, alongside brief context on bariatric surgery for patients whose disease severity exceeds what medication alone can address.

Anthropometric recognition

Overweight and obesity are most often first identified from BMI (weight in kg divided by height in m squared) at a routine visit, or from a patient presenting specifically for weight management. Waist circumference (measured at the midpoint between the lowest rib and the iliac crest) should be measured alongside BMI in every patient being assessed for obesity-related risk, since central (visceral) adiposity carries more cardiometabolic risk than the same BMI with a more peripheral fat distribution.^[1] Use ethnicity-specific BMI and waist-circumference thresholds where applicable — several Asian-ancestry populations reach clinically relevant adiposity risk at BMI and waist-circumference values below the standard cut-offs.^[2]

Physical signs of adiposity-related complications

• Acanthosis nigricans (velvety hyperpigmentation, typically at the neck or axillae) — a sign of insulin resistance.
• Hepatomegaly or other signs suggesting metabolic dysfunction-associated steatotic liver disease (MASLD).
• Abdominal wall hernias and intertrigo (skin-fold irritation/infection).
• Reduced joint mobility or gait changes suggesting osteoarthritis, particularly of the knees and hips.
• Large neck circumference, daytime somnolence, or witnessed apneic episodes suggesting obstructive sleep apnea.
• Elevated blood pressure, and other findings of the metabolic syndrome cluster (dyslipidemia, hyperglycemia).

• Family history of obesity and a genetic predisposition to weight gain — genetic risk does not mean weight cannot be managed, though it can make management more difficult.
• An obesogenic environment: energy-dense food availability, sedentary occupational and leisure patterns, and reduced sleep duration/quality.
• Chronic stress and inadequate sleep, both of which alter appetite-regulating hormones.
• Endocrine conditions that predispose to weight gain: hypothyroidism, Cushing syndrome, and polycystic ovary syndrome.
• Mental health conditions, including depression and binge eating disorder, and the medications used to treat them (see Assessment & Diagnosis for the specific medication list).
• Life-stage transitions associated with weight gain: pregnancy, menopause, and smoking cessation.
• Lower socioeconomic status and reduced access to affordable healthy food, safe spaces for physical activity, or obesity treatment coverage.
• Prior weight-loss attempts followed by regain ("weight cycling"), which is common and should not be treated as a sign of nonadherence.

History: identify the root drivers

A useful history goes beyond diet and exercise to identify what is actually driving a given patient’s weight, using Obesity Canada’s 4M framework.

A complete history also covers prior weight-loss attempts and their outcomes, precipitating events (pregnancy, injury, smoking cessation), readiness for change, and the patient’s own health and quality-of-life goals — obesity management works best when the plan is built around what the patient actually wants to achieve, not an externally imposed weight target.

Physical examination

• Vital signs, including blood pressure.
• Waist circumference, measured consistently at the midpoint between the lowest rib and the iliac crest.
• Target-organ signs: hepatomegaly, abdominal wall hernias, acanthosis nigricans, intertrigo.
• Assessment for genetic or syndromic causes of obesity when the history suggests one (early-onset severe obesity, hyperphagia, developmental delay).

Investigations

• Screen for the common obesity-related comorbidities: type 2 diabetes, dyslipidemia, hypertension, and gout.
• Liver enzymes, with liver ultrasound where MASLD is suspected clinically.
• Routine TSH screening is not indicated in an asymptomatic patient being assessed for obesity — test only when clinical findings suggest thyroid dysfunction.
• Sleep study where obstructive sleep apnea is suspected from history (snoring, witnessed apnea, daytime somnolence) or examination (large neck circumference).
• ECG, exercise testing, and echocardiography where cardiovascular risk or symptoms warrant them.
• Assess for gastroesophageal reflux and gallbladder disease where symptomatic.

Staging beyond BMI: the Edmonton Obesity Staging System

BMI alone should not be used to decide who needs treatment or how urgently. The Edmonton Obesity Staging System stages mortality and morbidity risk based on obesity-related medical, functional, and psychological impact, and is a better predictor of long-term outcomes than BMI alone.^[4]

Stage 2 or higher is the general threshold at which more aggressive treatment (pharmacotherapy, and bariatric surgery in eligible patients) is considered, rather than staged lifestyle intervention alone.

BMI classification

Medication history: drugs associated with weight gain

A focused medication review is one of the highest-yield, most pharmacist-relevant steps in the work-up of unexplained or accelerating weight gain — and in ongoing management, since starting one of these agents can undermine an otherwise-effective obesity treatment plan.^[5]

• Improve health outcomes and function related to adiposity — treat the complications, not just the number on the scale.
• Achieve at least 5% total body weight loss as the threshold generally associated with meaningful metabolic improvement, with further clinical benefit continuing at greater degrees of weight loss.
• Prevent, improve, or reverse specific obesity-related complications: type 2 diabetes/prediabetes, hypertension, dyslipidemia, obstructive sleep apnea, MASLD, knee osteoarthritis, and cardiovascular risk.
• Address the specific root drivers identified in the 4M assessment, not only caloric intake.
• Sustain results long-term — obesity management is planned as an ongoing chronic-disease strategy, never toward a fixed stop date.
• Set goals collaboratively with the patient, prioritizing function and quality of life alongside weight-related targets.

The 5As of obesity management

Obesity Canada’s 5As framework structures a weight-management conversation around the tenets of chronic disease management: patient education, self-management, and ongoing follow-up and support.^[1]

Nutrition

All structured, calorie-restricted diets produce comparable short-term weight loss in patients who adhere to them — no single named diet is superior, so the best diet for a given patient is the one that is culturally acceptable, affordable, nutritionally adequate, and sustainable for them. Refer to a dietitian for individualized planning where available. Caution patients that caloric restriction itself triggers neurobiological changes that favour increased appetite and weight regain — this is physiology, not a failure of discipline, and is part of why pharmacotherapy targets these same appetite-regulating pathways.

Physical activity

• Encourage at least 30 minutes of continuous or accumulated (minimum 10-minute bouts) activity on most days of the week; patients can start with 5- to 10-minute bouts and build up frequency, duration, and intensity over time.
• Exercise alone is not an effective primary weight-loss strategy, but it reduces visceral fat, improves cardiovascular fitness, helps preserve lean body mass during weight loss, and supports long-term weight maintenance.
• Resistance training is particularly important when combined with GLP-1/GIP pharmacotherapy, to help preserve lean muscle mass during rapid weight loss.
• A treadmill stress test should be considered before starting an exercise program in patients with elevated cardiovascular risk.

Psychological support

Cognitive behavioural therapy and related behavioural approaches (goal-setting, cognitive restructuring, relapse prevention) support adherence to lifestyle change, and are particularly useful for addressing internalized weight bias (reframing obesity as a medical condition, not a moral failure), setting realistic expectations, and preparing patients for the expected weight-loss plateau.

Counselling on GLP-1/GIP gastrointestinal tolerability

• Eat slowly, stop when full, and favour smaller, more frequent meals during dose escalation.
• Reduce high-fat and very large meals, which worsen nausea and delayed gastric emptying.
• Maintain adequate hydration, particularly if vomiting or diarrhea occurs.
• Reassure patients that GI symptoms are most prominent around each dose increase and typically ease within days to a couple of weeks — this is the main reason to titrate slowly rather than stopping therapy at the first sign of nausea.

Counselling on the chronic-disease treatment paradigm

Set expectations before starting pharmacotherapy: obesity medications are intended for long-term, ongoing use, and clinical trial evidence consistently shows weight regain and loss of associated health benefits when treatment is stopped, even with continued healthy lifestyle habits.^[2] Frame this the same way as continuing a statin or an antihypertensive — stopping is not a "graduation," and a planned discontinuation should be discussed with the prescriber rather than done unilaterally.

Breastfeeding

GLP-1 and dual GIP/GLP-1 receptor agonists are not recommended during breastfeeding — as large protein molecules they are expected to transfer into breast milk only in very small amounts and would likely be degraded in the infant’s GI tract, but human lactation data are not available to confirm this. Orlistat is not recommended during breastfeeding: systemic absorption is minimal, but it can cause fat-soluble vitamin deficiency, which is undesirable while breastfeeding. Naltrexone-bupropion is not recommended given limited transfer data and case reports of possible seizure in breastfed infants of patients taking bupropion.

Pediatrics and adolescents

Liraglutide (Saxenda) is approved for weight management in adolescents 12 years and older with obesity. Confirm the current adolescent-specific eligibility and dosing for any GLP-1/GIP agent before prescribing in this population, since pediatric obesity indications are expanding rapidly and should be verified against the current product monograph rather than assumed from the adult indication. Manage pediatric obesity within a dedicated pediatric obesity pathway with family involvement, not as a scaled-down adult protocol.

Renal and hepatic impairment

No dose adjustment is required for semaglutide, liraglutide, or tirzepatide based on renal function alone, but monitor renal function closely given the risk of dehydration-related acute kidney injury from GI adverse effects. Naltrexone-bupropion requires a reduced dose (1 tablet twice daily) in moderate-to-severe renal impairment or with a concomitant CYP2B6 inhibitor, a reduced dose (1 tablet once daily) in mild-to-moderate hepatic impairment, and is contraindicated in severe hepatic impairment or end-stage renal disease. Orlistat requires no dose adjustment in renal or hepatic impairment given minimal systemic absorption, but is contraindicated in chronic malabsorption syndrome or cholestasis.

Post-bariatric surgery drug review

Pharmacists reviewing medications after bariatric surgery should flag and adjust: oral bisphosphonates and NSAIDs (GI irritants, poorly tolerated and potentially harmful after gastric reduction), and sulfonylureas or insulin (high hypoglycemia risk as caloric intake and insulin sensitivity change rapidly post-operatively). Routine supplementation typically includes a complete multivitamin plus calcium, iron, vitamin B12, and vitamin D — confirm the specific regimen with the surgical/bariatric team, since requirements differ by procedure type.

Record baseline weight, BMI, and waist circumference at treatment initiation. During GLP-1/GIP dose titration, reassess tolerability at each scheduled dose-escalation step (approximately every 4 weeks); once a stable maintenance dose is reached, follow-up every 3 months is reasonable for most patients, more often if a comorbidity is being actively managed. Assess efficacy once the patient has been on the maintenance dose for approximately 12 weeks: continued treatment is generally reasonable if the patient has lost at least 5% of baseline body weight and is tolerating therapy; an inadequate response at this point should prompt the reassessment described in Treatment Failure & Next Steps.^[2] Recheck labs relevant to the patient’s specific comorbidities (HbA1c and lipid panel where diabetes or dyslipidemia is present, renal function periodically given the GI adverse-effect profile). For a patient on orlistat, monitor for fat-soluble vitamin deficiency and reinforce multivitamin timing at each visit. For a patient after bariatric surgery, coordinate ongoing nutritional and metabolic monitoring (CBC, ferritin, vitamin B12, calcium, vitamin D, bone density) with the surgical/bariatric follow-up program rather than duplicating it in isolation. At every visit, reinforce that this is a long-term treatment plan, and revisit the patient’s functional and quality-of-life goals alongside the weight-related ones.

1. Confirm adherence and correct injection technique/timing before assuming the medication itself is ineffective — a missed or improperly administered dose is a common, correctable cause of apparent treatment failure.
2. Assess response after approximately 12 weeks on the maintenance dose: if the patient has lost under 5% of baseline body weight despite confirmed adherence, the current agent is unlikely to produce clinically meaningful further benefit — discuss switching to a different agent/class or evaluating for bariatric surgery, rather than continuing indefinitely on an ineffective dose.
3. If gastrointestinal intolerance is the problem rather than lack of efficacy, extend the current titration step by an additional interval, or step back to the last-tolerated dose and re-attempt escalation more slowly, before concluding the agent has failed.
4. If GI intolerance persists despite genuinely slow titration, switch to an alternative agent within the GLP-1/GIP class, or to a different mechanism entirely (orlistat, naltrexone-bupropion), depending on what is driving the intolerance.
5. If weight regain occurs despite confirmed adherence, look specifically for a new medication-induced contributor (see the medication table in Assessment & Diagnosis), a change in one of the patient’s 4M root drivers, or a physiologic weight-loss plateau — a plateau is expected and, on its own, is not a reason to change an otherwise-tolerated, otherwise-effective therapy.
6. If the patient now meets bariatric-surgery eligibility criteria and an adequate trial of pharmacotherapy plus lifestyle intervention has not achieved the treatment targets, refer for surgical assessment rather than escalating pharmacotherapy indefinitely.

• Confusing a diabetes-dose GLP-1/GIP product (Ozempic, Victoza, Mounjaro) with its weight-management counterpart (Wegovy, Saxenda, Zepbound) — these have different maximum doses and titration schedules and, in Canada, are distinct authorized products; never substitute one for the other.
• Starting a GLP-1/GIP receptor agonist without first asking about a personal or family history of medullary thyroid carcinoma or MEN 2.
• Escalating the dose faster than the recommended schedule to "speed up" results — this worsens GI intolerance and adherence; the correct response to nausea is a slower titration, not a faster one.
• Treating obesity pharmacotherapy as a fixed-duration course rather than a long-term chronic-disease treatment, and being surprised when weight returns after stopping.
• Missing a medication-induced contributor to weight gain (a new antipsychotic, a corticosteroid course, insulin/sulfonylurea intensification) during a routine medication review.
• Recommending orlistat without counselling on fat-intake restriction and multivitamin timing, leading to severe, preventable GI adverse effects and early discontinuation.
• Using BMI alone, without waist circumference or a functional/complications-based assessment such as the Edmonton Obesity Staging System, to decide who needs treatment or how urgently.
• Missing naltrexone-bupropion contraindications (seizure disorder, uncontrolled hypertension, concurrent or recent opioid use) during a medication review.
• Recommending or dispensing compounded, unregulated, or non-Health-Canada-authorized weight-loss preparations rather than an approved product.

How to use this table: doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page. Weight-management-dose GLP-1/GIP products (Wegovy, Zepbound, Saxenda) are distinct, separately authorized products from the same molecules' diabetes-dose counterparts (Ozempic, Mounjaro, Victoza) -- confirm the patient is dispensed the correct product.

Human GLP-1 receptor agonists (weight-management dose)

Personal/family history of medullary thyroid carcinoma or MEN 2 is an absolute contraindication to every drug in this class.

Dual GIP/GLP-1 receptor agonist (weight-management dose)

Personal/family history of medullary thyroid carcinoma or MEN 2 is an absolute contraindication.

Lipase inhibitor

Non-systemic mechanism -- reduces dietary fat absorption rather than acting centrally on appetite.

Opioid antagonist / aminoketone antidepressant combination

A non-incretin oral option; screen carefully for the specific contraindications below before prescribing.

Noradrenergic appetite suppressant

Authorized in Canada for short-term (a few weeks) monotherapy only -- not a long-term chronic-disease treatment the way the incretin-based agents above are. The fixed-dose combination phentermine-topiramate (Qsymia) is not authorized for sale in Canada.

Melanocortin-4 receptor agonist (rare monogenic/syndromic obesity only)

Reserved for obesity caused by specific confirmed genetic conditions -- Bardet-Biedl syndrome, or POMC, PCSK1, or LEPR deficiency -- and outside the scope of the general algorithm in this chapter; specialist-initiated.