Uses of anorectics drugs
Anorectic drugs (appetite suppressants) are used primarily to help reduce food intake in the management of obesity. They work through various mechanisms - some act centrally on the hypothalamus to suppress appetite, others increase satiety signals or reduce fat absorption.
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Here is a thorough, textbook-based overview of anorectic (antiobesity / appetite-suppressant) drugs:
Anorectic (Antiobesity) Drugs
Anorectics are agents that suppress appetite or reduce caloric absorption and are used to treat obesity. Drug therapy is considered when BMI > 30 kg/m², or > 27 kg/m² with obesity-related comorbidities (hypertension, type 2 diabetes, dyslipidemia), and when diet, exercise, and behavioural therapy alone have been insufficient.
Classification & Mechanisms
1. Sympathomimetic Amines (Centrally Acting - Noradrenergic)
These drugs act in the CNS (hypothalamus) to increase norepinephrine (NE) and dopamine release, suppressing appetite.
| Drug | Notes |
|---|---|
| Phentermine | Most widely used; approved short-term (<12 weeks) due to addiction potential and cardiovascular toxicity. Dose: 30-37.5 mg/day PO. |
| Diethylpropion | Similar mechanism; increases NE/dopamine, approved for short-term use. |
| Phentermine + Topiramate (Qsymia) | Combination - phentermine suppresses appetite; topiramate increases GABA and adds satiety. Dose: 3.75-15 mg / 23-92 mg PO. Contraindicated in pregnancy. |
Adverse effects: Increased blood pressure and heart rate, arrhythmias, insomnia, anxiety, dry mouth, headache.
- Lippincott Illustrated Reviews Pharmacology, p. 757
2. GI Lipase Inhibitor (Peripherally Acting)
| Drug | Notes |
|---|---|
| Orlistat (Xenical, Alli) | Inhibits gastric and pancreatic lipases → reduces dietary fat absorption by ~30% → decreases caloric intake. Dose: 60-120 mg TID PO. The only drug approved for long-term use and available OTC. |
Adverse effects: Oily spotting, flatulence, fecal urgency/incontinence, decreased absorption of fat-soluble vitamins (A, D, E, K) - supplement required.
- Katzung's Basic and Clinical Pharmacology, 16th Edition
3. GLP-1 Receptor Agonists (Incretin-Based)
These agents slow gastric emptying and increase satiety signals.
| Drug | Notes |
|---|---|
| Liraglutide (Saxenda) | GLP-1 agonist; subcutaneous injection. FDA-approved for chronic weight management. |
| Semaglutide (Wegovy) | Dose: 2.4 mg/week SC or daily oral form. Most effective current pharmacotherapy for obesity. |
| Tirzepatide | Dual GLP-1 and GIP agonist (insulinotropic); shown to produce greater weight loss than semaglutide in Phase 3 trials. |
Adverse effects: Nausea, vomiting, pancreatitis, hypoglycemia, acute gallbladder disease, elevated heart rate.
- Lippincott Illustrated Reviews Pharmacology, p. 757
4. Combination Opioid Antagonist + Antidepressant
| Drug | Notes |
|---|---|
| Naltrexone + Bupropion (Contrave) | Bupropion stimulates POMC neurons in the hypothalamus; naltrexone blocks autoinhibitory feedback on the melanocortin system → combined appetite suppression via the mesolimbic reward pathway. Dose: 32 mg / 360 mg PO. |
Adverse effects: Nausea, headache, dizziness, dry mouth, constipation, suicidal ideation (black box warning).
- Lippincott Illustrated Reviews Pharmacology, p. 757
5. Melanocortin Agonist
| Drug | Notes |
|---|---|
| Setmelanotide | Melanocortin-4 receptor agonist; corrects rare genetic deficiencies in the leptin-melanocortin pathway (e.g., POMC deficiency, LEPR deficiency). Not a general-population drug. |
Adverse effects: Nausea, skin reactions (injection site).
- Katzung's Basic and Clinical Pharmacology, 16th Edition
6. Withdrawn / Historically Used Drugs
| Drug | Reason Withdrawn |
|---|---|
| Lorcaserin (5-HT2C agonist) | Withdrawn due to possible carcinogenicity |
| Sibutramine | Withdrawn due to increased cardiovascular events (MI, stroke) |
| Fenfluramine / Dexfenfluramine | Withdrawn due to cardiac valvulopathy and pulmonary hypertension |
Indications Summary
| Indication | Recommended Agent(s) |
|---|---|
| Obesity (BMI >30) - short-term | Phentermine, diethylpropion |
| Obesity (BMI >30) - long-term | Orlistat, liraglutide, semaglutide, naltrexone/bupropion, phentermine/topiramate |
| Obesity with hypertension | Avoid phentermine; prefer orlistat, GLP-1 agonists |
| Obesity with diabetes | GLP-1 agonists (semaglutide, liraglutide, tirzepatide) - dual benefit |
| Rare genetic obesity (POMC/LEPR deficiency) | Setmelanotide |
Key Contraindications
- Phentermine / sympathomimetics: Uncontrolled hypertension, cardiovascular disease, glaucoma, hyperthyroidism, history of drug abuse, MAOIs.
- Phentermine/topiramate: Pregnancy (teratogenic - oral clefts).
- Orlistat: Chronic malabsorption syndrome, cholestasis.
- GLP-1 agonists: Personal/family history of medullary thyroid carcinoma, MEN type 2.
- Naltrexone/bupropion: Seizure disorders, eating disorders (anorexia/bulimia), MAOIs.
Recent Evidence Note
A 2026 Cochrane systematic review (PMID: 42318855) examined the long-term effects of weight-reducing drugs specifically in patients with hypertension, reinforcing that agent selection must account for cardiovascular risk profile.
Sources: Katzung's Basic and Clinical Pharmacology 16e | Lippincott Illustrated Reviews Pharmacology | Textbook of Family Medicine 9e | Kaplan & Sadock's Comprehensive Textbook of Psychiatry
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