Obesity
Clinical Snapshot
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.
Recognize the Condition
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).
Risk Factors
- 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.
Red Flags & Refer
Most red flags in this chapter relate specifically to patients on GLP-1 or dual GIP/GLP-1 receptor agonist therapy — these agents carry a real, if low-frequency, risk of pancreatitis, gallbladder disease, and bowel obstruction/gastroparesis, so know these triggers before prescribing, not only when a patient calls with symptoms.[3]
- Severe, persistent abdominal pain (with or without radiation to the back) in a patient on a GLP-1/GIP agonist — evaluate urgently for acute pancreatitis and discontinue the agent immediately if suspected; do not restart if pancreatitis is confirmed.
- Signs of gallbladder disease — right-upper-quadrant pain, jaundice, or fever with abdominal pain — GLP-1/GIP agonists increase the risk of gallstones and cholecystitis.
- Personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type 2 (MEN 2) — this is an absolute contraindication to starting any GLP-1 or dual GIP/GLP-1 receptor agonist (semaglutide, liraglutide, or tirzepatide); screen for this before initiating, not after.
- Severe gastrointestinal intolerance preventing adequate oral intake or hydration — assess for dehydration and acute kidney injury, and hold or discontinue the agent rather than continuing to escalate the dose.
- Signs of bowel obstruction — severe abdominal distension, persistent vomiting, or absence of bowel movements/flatus — a rare but serious effect of slowed GI motility with these agents.
- New or worsening suicidal ideation or significant mood change on any weight-loss medication — evaluate urgently and involve mental health support.
- Symptoms of an acute obesity-related complication requiring its own emergency pathway — chest pain/ACS symptoms, decompensated heart failure, or severe hypoxemia from obstructive sleep apnea — refer through the appropriate acute pathway rather than managing as routine obesity follow-up.
Assessment & Diagnosis
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.
The 4Ms of root-driver assessment
Mechanical
Physical issues that limit activity or contribute to weight gain — joint pain, mobility limitations, obstructive sleep apnea.
Mental
Mood, anxiety, binge eating or other disordered eating patterns, ADHD, insomnia, and internalized weight bias.
Metabolic
Endocrine and metabolic contributors — hypothyroidism, PCOS, and medications associated with weight gain (see the medication table below).
Milieu (social)
Social and environmental context — food access and affordability, support systems, culture, and insurance/coverage for obesity treatment.
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 | Assessment of weight-related health, mental health, and function |
|---|---|
| 0 | No obesity-related risk factors, physical symptoms, psychological symptoms, or functional limitations. |
| 1 | Subclinical risk factors (e.g., borderline hypertension, impaired fasting glucose), mild physical symptoms not yet requiring treatment, or mild psychological symptoms or impairment of well-being. |
| 2 | Established obesity-related comorbidities requiring medical intervention (e.g., hypertension, type 2 diabetes, sleep apnea, osteoarthritis), or moderate psychological symptoms or functional limitations. |
| 3 | Significant end-organ damage (e.g., diabetic complications, heart failure), significant psychological symptoms, or significant functional limitations. |
| 4 | Severe, potentially end-stage disability from obesity-related comorbidities, or severe psychological or functional impairment. |
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
| Category | BMI (kg/m2) |
|---|---|
| Overweight | 25.0 to 29.9 (lower in several Asian-ancestry populations — use ethnicity-specific thresholds where applicable) |
| Obesity, class I | 30.0 to 34.9 |
| Obesity, class II | 35.0 to 39.9 |
| Obesity, class III (severe) | 40 or greater |
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]
| Class / indication | Example drugs | Mechanism | Possible lower-weight-gain alternatives |
|---|---|---|---|
| Antidepressants | Amitriptyline, mirtazapine, and other tricyclic/tetracyclic agents | Attenuated serotonin-mediated signal transduction and reduced basal metabolic rate; degree varies by agent and duration of use. | Bupropion, fluoxetine, sertraline |
| Antipsychotics | Loxapine (first-generation); olanzapine, clozapine, quetiapine, risperidone (second-generation) | Dopamine D2 and serotonin receptor blockade increases appetite; effect is agent- and dose-dependent. | Aripiprazole, ziprasidone |
| Corticosteroids | Prednisone, dexamethasone | Stimulates appetite and causes hyperinsulinemia, promoting fat deposition. | Use the lowest effective dose and shortest duration; no like-for-like drug substitute within the corticosteroid class itself. |
| Hormonal therapy | Medroxyprogesterone acetate (injectable) and other estrogen/progesterone/androgenic agents | Possible increased appetite or altered body fat distribution; mechanism not fully defined. | For contraception specifically: a barrier method or a copper IUD avoids hormonal exposure entirely. |
| Antihyperglycemic agents | Insulin, sulfonylureas (glyburide, gliclazide), pioglitazone | Reduced glycosuria and increased insulin exposure promote fat mass accumulation. | Metformin, acarbose, a DPP-4 inhibitor, a GLP-1 receptor agonist (see Drug Tables), an SGLT2 inhibitor |
| Mood stabilizers / anticonvulsants | Lithium carbonate, valproic acid, carbamazepine | Varies by agent — lithium causes polydipsia and sodium/water retention; valproate enhances GABA activity and stimulates carbohydrate intake. | Topiramate, lamotrigine (both weight-neutral-to-weight-reducing options where psychiatrically appropriate) |
Treatment Targets
- 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.
Choose Initial Treatment
Who is a pharmacotherapy candidate
Offer pharmacotherapy, as an adjunct to behavioural/lifestyle intervention (never as monotherapy), to adults with a BMI of 30 kg/m2 or greater, or a BMI of 27 kg/m2 or greater with at least 1 weight-related comorbidity (e.g., hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea, or established cardiovascular disease) — use ethnicity-adjusted BMI thresholds where applicable.[2]
First-line pharmacotherapy
1st line semaglutide (Wegovy) 2.4 mg subcutaneously weekly or tirzepatide (Zepbound) up to 15 mg subcutaneously weekly — both are co-equal first-line options given their substantially greater efficacy compared with older agents.[2] The choice between them is generally guided by patient preference, tolerability, cost/coverage, and any obesity-related comorbidity where one agent has specific supporting evidence — semaglutide is also authorized to reduce the risk of non-fatal myocardial infarction in patients with established cardiovascular disease[6], while tirzepatide is also authorized for moderate to severe obstructive sleep apnea in patients with obesity.[7]
Alternative pharmacotherapy
Alternative liraglutide (Saxenda) 3 mg subcutaneously daily, naltrexone-bupropion, or orlistat — use when a GLP-1/GIP agonist is contraindicated, not tolerated despite slow titration, or not accessible because of cost or coverage. Match the specific alternative to the patient: naltrexone-bupropion is a reasonable option in a patient also working on smoking cessation given bupropion’s dual role, but is contraindicated in seizure disorder; orlistat avoids injections entirely but requires strict fat-intake counselling to be tolerable.
Special-situation pharmacotherapy
Special situation phentermine, authorized in Canada for short-term (a few weeks) monotherapy only — useful as a brief adjunct in a specific, limited circumstance, never as a substitute for long-term chronic-disease pharmacotherapy and never combined with any other weight-loss drug.
Absolute contraindication — do not use any GLP-1 or dual GIP/GLP-1 receptor agonist (semaglutide, liraglutide, or tirzepatide, at any dose or for any indication) in a patient with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) — select orlistat or naltrexone-bupropion instead if pharmacotherapy is otherwise appropriate for this patient.
Titrate to tolerability
Always start GLP-1/GIP agonist therapy at the lowest initiation dose and follow the specific titration schedule in Drug Tables — the great majority of gastrointestinal adverse effects are transient and dose-related, and slow, guideline-directed titration (not a fixed calendar) is the main tool for keeping a patient on effective therapy.
When pharmacotherapy alone is not enough
Refer for bariatric surgery assessment in patients with a BMI of 40 kg/m2 or greater, or a BMI of 35 kg/m2 or greater with a significant obesity-related comorbidity, particularly when an adequate trial of pharmacotherapy plus lifestyle intervention has not achieved the treatment targets — bariatric surgery remains the most effective option for eligible patients with severe obesity and should be raised as a parallel option, not only a last resort after medication has been exhausted.
Non-Pharmacologic Treatment
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]
The 5 steps
Ask
Ask permission to discuss weight, non-judgmentally, and explore readiness for change before proceeding.
Assess
Assess BMI, waist circumference, Edmonton Obesity Staging System stage, and root drivers (4Ms) — BMI alone should never be the sole basis for the assessment.
Advise
Advise on health risks, the benefit of even modest weight loss, the need for a long-term strategy, and the available treatment options.
Agree
Agree on realistic weight-loss expectations and a specific treatment plan the patient actually wants to pursue.
Assist
Assist in identifying and addressing barriers, connect the patient with appropriate resources and providers, and arrange regular follow-up.
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.
Special Populations
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.
Monitoring & Follow-Up
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.
Common Errors to Avoid
- 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.
Clinical Decision Algorithm
Drug Tables
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.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Semaglutide (Wegovy) | Initiation: 0.25 mg SC once weekly x4 weeks Titration: 0.5 mg weekly x4wk, then 1 mg weekly x4wk, then 1.7 mg weekly x4wk Maintenance: 2.4 mg SC once weekly Pediatrics/adolescents: Not established for this product -- confirm current Health Canada labelling before considering use under 18 years | Nausea, vomiting, diarrhea, constipation (most common, dose-related); rare acute pancreatitis, cholelithiasis/cholecystitis, gastroparesis, bowel obstruction | Delays gastric emptying, may affect absorption of concurrent oral drugs including oral contraceptives; additive hypoglycemia risk with insulin/sulfonylurea | Distinct product/dose from Ozempic (diabetes indication, max 2 mg weekly). Also authorized to reduce the risk of non-fatal myocardial infarction in patients with established cardiovascular disease and elevated BMI. |
| Liraglutide (Saxenda) | Initiation: 0.6 mg SC once daily x1 week Titration: Increase by 0.6 mg at intervals of at least 1 week (1.2 mg, 1.8 mg, 2.4 mg) Maintenance: 3 mg SC once daily Adolescents (12 years and older): Same titration schedule to the 3 mg SC daily maintenance dose -- confirm current eligibility criteria | Nausea, vomiting, diarrhea, constipation, decreased appetite, injection-site reactions | Delays gastric emptying, may affect absorption of concurrent oral drugs including oral contraceptives; additive hypoglycemia risk with insulin/sulfonylurea | Distinct product/dose from Victoza (diabetes indication, max 1.8 mg daily). Daily injection -- lower adherence than the once-weekly agents. Evaluate after 12 weeks on the 3 mg maintenance dose; discontinue if under 5% baseline weight loss. |
Dual GIP/GLP-1 receptor agonist (weight-management dose)
Personal/family history of medullary thyroid carcinoma or MEN 2 is an absolute contraindication.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Tirzepatide (Zepbound) | Initiation: 2.5 mg SC once weekly x4 weeks (initiation dose only, not intended for weight-loss efficacy) Titration: Increase in 2.5 mg increments at intervals of at least 4 weeks as tolerated Maintenance: Individualized, 5 mg to a maximum of 15 mg SC once weekly Pediatrics: Not established under 18 years of age | Nausea, vomiting, diarrhea, constipation, injection-site reactions; rare acute pancreatitis, cholelithiasis/cholecystitis, gastroparesis, bowel obstruction | Delays gastric emptying, may affect absorption of concurrent oral drugs including oral contraceptives; additive hypoglycemia risk with insulin/sulfonylurea | Distinct product from Mounjaro (diabetes indication). Also authorized for moderate to severe obstructive sleep apnea in adults with obesity. Co-equal 1st-line option with semaglutide. |
Lipase inhibitor
Non-systemic mechanism -- reduces dietary fat absorption rather than acting centrally on appetite.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Orlistat | Adults: 120 mg PO with each fat-containing meal, up to 3 times daily (during or up to 1 hour after the meal) Pediatrics: Not established for routine pediatric use -- specialist-directed only | Oily spotting, fecal urgency, flatus with discharge, steatorrhea -- worse with high-fat meals | Reduces absorption of fat-soluble vitamins (A, D, E, K); separate cyclosporine dosing by at least 2 hours from orlistat | Take a multivitamin at least 2 hours before or after orlistat, or at bedtime. Contraindicated in chronic malabsorption syndrome or cholestasis. Minimal systemic absorption. |
Opioid antagonist / aminoketone antidepressant combination
A non-incretin oral option; screen carefully for the specific contraindications below before prescribing.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Naltrexone / Bupropion (Contrave) | Week 1: 1 tablet (8 mg/90 mg) PO each morning Week 2: 1 tablet PO BID Week 3: 2 tablets each morning + 1 tablet each evening Maintenance (week 4 onward): 2 tablets PO BID (16 mg/180 mg BID) Renal/hepatic adjustment: 1 tablet PO BID in moderate-severe renal impairment or with a CYP2B6 inhibitor; 1 tablet PO once daily in mild-moderate hepatic impairment Pediatrics: Not established | Nausea, headache, insomnia, dizziness, dry mouth, constipation, increased blood pressure/heart rate that may offset some of the cardiovascular benefit of weight loss | Contraindicated with MAOIs, thioridazine, and concurrent opioid therapy (precipitates opioid withdrawal); requires 7 opioid-free days before starting | Contraindicated in seizure disorder, uncontrolled hypertension, severe hepatic impairment, and end-stage renal disease. Avoid or minimize alcohol given seizure-threshold effects. |
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.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Phentermine (Ionamin) | Adults: 15-30 mg PO once daily, before breakfast or 10-14 hours before bedtime; short-term use only (a few weeks) Pediatrics: Not established | Insomnia, dry mouth, restlessness, irritability, tremor, headache, increased heart rate/blood pressure | Contraindicated with MAOIs (within 14 days) -- hypertensive crisis risk; additive stimulation with other sympathomimetic agents | Do not combine with any other anti-obesity drug. Contraindicated in cardiovascular disease, uncontrolled hypertension, hyperthyroidism, glaucoma, and a history of drug abuse. |
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.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Setmelanotide (Imcivree) | Adults and children 6 years and older: Individually titrated, up to 3 mg SC once daily | Injection-site reactions, nausea, skin hyperpigmentation, headache | None significant | For confirmed monogenic/syndromic obesity only, in adults and children 6 years and older, under specialist direction -- not for the general obesity population covered by the rest of this chapter. |
References
- Obesity in adults: a clinical practice guideline — CMAJ, Obesity Canada (Wharton S, Lau DCW, Vallis M, et al.). CMAJ 2020;192(31):E875-E891
- Pharmacotherapy for obesity management in adults: 2025 clinical practice guideline update — CMAJ, Obesity Canada (Pedersen SD, Manjoo P, Dash S, et al.). CMAJ 2025;197(27):E797-E809
- Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss — JAMA (Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M). JAMA 2023;330(18):1795-1797
- A proposed clinical staging system for obesity — International Journal of Obesity (Sharma AM, Kushner RF). Int J Obes (Lond) 2009;33(3):289-295
- Medications that cause weight gain and alternatives in Canada: a narrative review — Diabetes, Metabolic Syndrome and Obesity (Wharton S, Raiber L, Serodio KJ, Lee J, Christensen RAG). Diabetes Metab Syndr Obes 2018;11:427-438
- Semaglutide and cardiovascular outcomes in obesity without diabetes — New England Journal of Medicine (Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.). N Engl J Med 2023;389(24):2221-2232
- Tirzepatide once weekly for the treatment of obesity — New England Journal of Medicine (Jastreboff AM, Aronne LJ, Ahmad NN, et al.). N Engl J Med 2022;387(3):205-216
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.