Drugs approved for weight loss in Canada: Important considerations

Obesity is a chronic disease with multiple causes: biological factors, psychological influences (stress, eating disorders), an obesogenic environment and often a hereditary component. 

Visit canadian standards 2025 The new guidelines state that pharmacotherapy is becoming an important component in the management of obesity when weight impairs health. Six drugs are now authorized by Health Canada for long-term weight management:

1. liraglutide,
2. naltrexone/bupropion,
3. orlistat,
4. semaglutide,
5. tirzepatide
6. and setmelanotide.

The aim is not to «make people skinny», but to improve metabolic, mechanical and mental health.

Category 1: naltrexone/bupropion: acts on appetite and reward

How does it work?

The first class comprises Contrave®, a fixed combination of naltrexone and bupropion. In the brain, bupropion stimulates pro-opiomelanocortin neurons in the hypothalamus, reducing appetite and increasing energy expenditure. Naltrexone blocks certain opioid receptors involved in reward and addiction; this action complements that of bupropion and reduces the compulsive urge to eat. Imaging studies have shown that the naltrexone/bupropion combination attenuates the hypothalamus' reactivity to food signals, while strengthening brain regions involved in self-control. The result is a reduction in hunger and cravings, with no stimulant effect.

Prescription conditions

The pharmacotherapeutic guide 2025 recommends this medication in adults with a BMI ≥ 27 kg/m² with comorbidity or ≥ 30 kg/m², in association with lifestyle modification. Contraindications include opioid use, uncontrolled hypertension, epilepsy, eating disorders (anorexia or bulimia), pregnancy and abrupt discontinuation of alcohol or sedatives. Titration is progressive to minimize adverse effects: an initial dose of 8/90 mg per day is increased weekly to 16/180 mg twice daily.

Efficacy and side effects

A randomized study of 1,742 patients showed that the naltrexone/bupropion combination, combined with behavioral changes, resulted in an average weight loss of 6.1 % in 56 weeks versus 1.3 % with placebo. Common side effects included nausea, headache, constipation, dizziness and dry mouth; 20 % of participants discontinued treatment due to adverse effects. To manage these, it is advisable to take the tablets with food (not fat) and to increase the dosage slowly; discontinuation should be gradual to avoid withdrawal symptoms. It is important to monitor blood pressure and mood, as bupropion can cause agitation and insomnia.

Category 2: incretin analogues: mimicking natural intestinal hormones

GLP-1 and GIP: mechanisms and authorized molecules

Incretins are hormones produced after a meal to signal satiety. Analogues of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) extend this response. In pharmacology, These molecules slow gastric emptying, stimulate insulin when blood sugar levels are high, inhibit glucagon secretion and act on the brain to increase the sensation of satiety. In this way, they help to reduce calorie intake without stimulating the basic metabolism.

GLP-1 drugs

• Liraglutide (Saxenda®) daily injection. In a trial involving 3731 adults, a dose of 3 mg/day combined with behavioral support resulted in an average weight loss of 8 % in 56 weeks, compared with 2.6 % in the placebo group. Frequent side effects (nausea, diarrhea, constipation) can be mitigated by gradually increasing doses and eating smaller meals. Rarely, gallstones or pancreatitis have been reported.
• Semaglutide (Wegovy®) weekly injection. In the STEP 1 study (1961 participants with BMI ≥ 30 or ≥ 27 with comorbidity), a weekly dose of 2.4 mg resulted in a weight loss of 14.9 % in 68 weeks versus 2.4 % with placebo. The main side effects are transient nausea, vomiting and diarrhea; gallstones and pancreatitis are rare. Health Canada has also approved semaglutide to reduce cardiovascular events in adults with cardiovascular disease and BMI ≥ 27 kg/m².
• Tirzepatide (Zepbound®) GIP/GLP-1 dual agonist, weekly injection. In a trial involving 2539 adults without diabetes, mean weight loss was 15 % to 20.9 % depending on dose (5 to 15 mg/week), compared with 3.1 % with placebo. Side effects are mainly gastrointestinal (nausea, diarrhea, constipation) and occur mainly with dose escalation. Cholecystitis is rare.

Prescribing conditions and precautions

Incretin analogues are indicated in adults with a BMI ≥ 30 kg/m² or ≥ 27 kg/m² with adiposity-related complications (hypertension, dyslipidemia, prediabetes, sleep apnea, etc.). Contraindications include pregnancy, breastfeeding and a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Dose escalation should be cautious to reduce nausea; eating smaller, low-fat meals can limit digestive symptoms. Biliary and pancreatic functions should be monitored.

Orlistat: lipase inhibitor

L’orlistat (Xenical®) is a reversible inhibitor of gastric and pancreatic lipases. By binding to the serine of their active site, it prevents the hydrolysis of triglycerides; the absorption of fatty acids and monoglycerides is reduced and part of the dietary fat is eliminated. eliminated in the stool. Orlistat is taken at a dose of 120 mg three times a day with fat-containing meals. In a meta-analysis involving over 10,000 participants, orlistat produced an additional weight loss of around 2.9 % after one year, compared with placebo. Side effects are mainly digestive (oily stools, fecal urgency and greasy spots) and occurred in 15 to 30 % of participants; they can be mitigated by reducing fat intake. Orlistat is contraindicated in cases of malabsorption syndrome., cholestasis and during pregnancy.

Side effects: what to look out for and how to manage them

Prescription drugs versus «natural» supplements: why caution is called for

Prescription weight-loss products are intended for people whose weight represents a health risk, and must be used under medical supervision, with physical activity and calorie reduction. So-called «natural» or over-the-counter products are not subject to the same rigor: some supplements contain undeclared ingredients or contaminants, while others are mixed with prescription drugs. Online purchases of unauthorized weight-loss products, or the combination of several products, can lead to serious adverse effects. The belief that a product is safe because it is «natural» is false; Health Canada reports that concentrated plant extracts such as ephedra or bitter orange can cause severe cardiovascular reactions. It is therefore essential to take only evaluated and approved treatments, and to discuss them with a healthcare professional.

Treatment duration and discontinuation management

Anti-obesity drugs should be considered as long-term treatments. Trials show that stopping an incretin after several months results in rapid weight regain: in the semaglutide study, participants who stopped the drug after a 20-week «run-in» regained 6.9 % of their weight in 48 weeks, while those who continued therapy continued to lose weight. A similar pattern was observed with tirzepatide: participants who stopped treatment regained 14 % of their weight in one year.. The duration of treatment therefore depends on tolerance, efficacy and the patient's objectives. Discontinuation should be planned with a doctor and accompanied by intensive lifestyle monitoring to minimize weight regain.

Integration into an overall weight loss program

Medication can never replace work on lifestyle habits. Treatment must be part of a personalized program that includes :

• Adapted nutrition A balanced diet, rich in fiber and low in ultra-processed foods, adjusted according to energy needs and preferences. Adequate protein intake promotes satiety and preserves muscle mass.
• Physical activity Aim for at least 150 minutes of moderate activity per week. Activity increases energy expenditure, improves insulin sensitivity and reduces cravings.
• Psychological support Treatments such as cognitive-behavioral therapy, mindfulness or hypnosis (mentioned by Dr. Mazur) help to understand the emotional triggers of cravings and to develop strategies for coping with them. Hypnosis can reinforce adherence to habit changes and alleviate food dependency.
• Regular medical check-ups These include evaluating drug efficacy, adjusting dosage, monitoring metabolic parameters (blood pressure, blood sugar, lipids), detecting adverse effects and supporting motivation.

What are the prospects for new-generation drugs?

Innovation continues. Molecules that combine several satiety hormones are showing promise. Retatrutide, a GLP-1, GIP and glucagon receptor agonist, showed in phase 2 a weight loss of 24 % in 48 weeks. This triple therapy may improve lipid burning by increasing fatty acid oxidation in the liver, decreasing lipogenesis and stimulating lipolysis via GIP receptors. Trials also suggest a reduction in hepatic steatosis and improved insulin sensitivity. Cagrilintide, an amylin analogue, mimics another hormone produced after meals; combined with semaglutide (the «CagriSema» formula), it is in development and could offer superior weight loss to GLP-1 alone. These treatments are not yet available in Canada, but are generating debate about access, cost and the ethics of using powerful weight-loss drugs versus traditional public health approaches.

Precautions and refusal to prescribe

Before prescribing, doctors carefully weigh up the benefits and risks. Some patients may want a specific medication, but it may be contraindicated (e.g. pregnancy, unstabilized psychotic illness, opioid use, history of pancreatitis). In such cases, the healthcare professional must explain why the requested option is unsuitable, and suggest alternatives. A relationship of trust is essential; the patient remains the final decision-maker, but the aim is to protect his or her health. It is common practice to reschedule a second meeting to allow the patient to reflect and the clinician to review the patient's file and test results.

Realistic results and objectives

Dr. Mazur reminds us that goals must be realistic and individualized. The following benchmarks are taken from Canadian guides:

• BMI 25-30 without comorbidity Weight loss: a weight loss of around 5 % is often enough to reduce the risk of disease; maintenance can be achieved without medication.
• BMI 25-30 with prediabetes Aiming for 5 to 10 % of loss helps prevent progression to diabetes.
• BMI 30-40 or BMI ≥ 27 with comorbidities A loss of 5 to 10 % improves blood pressure, dyslipidemia and sleep apnea, and reduces joint pain; above 10 %, there's better resolution of sleep apnea syndromes and a reduction in antihypertensive medication.
• BMI ≥ 27 with type 2 diabetes A 15 % reduction in weight can lead to remission of diabetes.
• BMI ≥ 35 with comorbidities For example, weight loss targets of 20 to 30 % may be necessary to improve health, without aiming for a «normal» weight.

Weight loss must be accompanied by regular monitoring. The ultimate goal is to achieve a weight at which the person feels comfortable and which improves their health, not necessarily to enter an «ideal» weight range. Continuity of care, self-acceptance and sustainability of changes take precedence over obsession with thinness.

Conclusion

Pharmacotherapy for obesity has entered a new era. Six drugs are approved in Canada: naltrexone/bupropion, orlistat, liraglutide, semaglutide, tirzepatide and setmelanotide. Each acts through a different mechanism - modulation of reward circuits, inhibition of fat absorption or mimicking of gut hormones - and should be prescribed after careful evaluation and in association with lifestyle modifications. Side effects, although often transient, require monitoring and dose adjustment. New agents such as retatrutide or amylin analogues herald major advances, but are already raising debate about the accessibility and proper use of these therapies.

By choosing to follow a drug treatment, people living with obesity gain an additional option for achieving realistic health goals. This tool should be used with caution, with proper information and professional guidance, and as part of an overall program of diet, physical activity and psychological support.