Body weight regulation goes beyond diet and exercise. Many medications and supplements can increase or decrease body weight by affecting digestion, appetite, hormones, or metabolism. Some are prescribed directly for weight management, while others cause weight changes as side effects.
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Below are two sections—Weight Gain and Weight Loss—with their mechanisms explained.
Medications & Supplements Linked to Weight Gain
These agents often increase appetite, promote fat storage, or reduce activity.
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1. Antihistamines
Examples: Cyproheptadine (Periactin), diphenhydramine, cetirizine.
Mechanism:
Block histamine H1 receptors, which normally contribute to satiety signaling in the brain.
Result: increased appetite and food intake.
Sedative effects reduce energy expenditure.
Note: Older (first-generation) antihistamines and some newer ones (cetirizine) are more likely to cause weight gain than non-sedating options (loratadine, fexofenadine).
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2. Appetite Stimulants
Cyproheptadine (Periactin): Dual antihistamine/serotonin-blocking action → strong appetite boost.
Megestrol (Megace): Synthetic progestin, often used in cancer or HIV cachexia to promote weight gain.
Mirtazapine (Remeron): Antidepressant that antagonizes histamine & serotonin receptors → increased appetite and carb craving.
Dronabinol (Marinol): Synthetic THC, activates cannabinoid receptors → appetite stimulation (“munchies” effect).
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3. CorticosteroidsÂ
Examples: Prednisone, dexamethasone.
Mechanism:
Increase appetite.
Stimulate glucose production and fat storage.
Cause fluid retention and body fat redistribution (“moon face,” abdominal fat).
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4. Antidepressants & Antipsychotics
SSRIs: Paroxetine, sertraline may increase appetite.
Tricyclics (Amitriptyline, Nortriptyline): Increase cravings for carbohydrates.
Antipsychotics (Olanzapine, Clozapine, Risperidone): Strongly associated with significant weight gain, partly due to histamine and dopamine receptor effects.
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5. Diabetes Medications That Promote Weight Gain
Insulin therapy: Directly promotes glucose uptake into fat and muscle → storage.
Sulfonylureas (Glipizide, Glyburide): Stimulate insulin release → risk of weight gain.
Thiazolidinediones (Pioglitazone, Rosiglitazone): Improve insulin sensitivity but cause fat accumulation and fluid retention.
-Omega-3 fatty acids: Can help restore appetite in certain illness-related malnutrition.
-Vitamin D & B-complex: Support metabolism and energy balance; useful if deficiencies are present (not direct weight-gain agents).
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Medications & Supplements Linked to Weight Loss
These work by suppressing appetite, blocking nutrient absorption, or boosting energy expenditure.
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1. Anti-Diabetic Medications (Weight-Loss Promoting)
Metformin:
Reduces liver glucose production.
Improves insulin sensitivity.
May reduce appetite → modest weight loss.
GLP-1 Receptor Agonists (Ozempic/Semaglutide, Saxenda/Liraglutide, Tirzepatide/Mounjaro):
Mimic GLP-1 hormone, slowing gastric emptying and enhancing satiety signals.
Result: less food intake + improved blood sugar control.
Very effective in both diabetes and obesity.
SGLT2 Inhibitors (Empagliflozin, Dapagliflozin):
Block glucose reabsorption in kidneys → excess sugar excreted in urine.
Result: calorie loss and modest weight reduction.
Acarbose:
Inhibits enzymes that break down carbs.
Delays absorption, reduces blood sugar spikes → less fat storage.
Side effects: bloating, gas.
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2. Prescription Weight-Loss Drugs
Orlistat (Xenical, Alli): Blocks fat absorption (~30%). Side effect: oily stools, fat-soluble vitamin loss.
Phentermine: Stimulates CNS, suppresses hunger, may increase BP/HR.
Phentermine/Topiramate (Qsymia): Combination therapy for enhanced effect.
Naltrexone-Bupropion (Contrave): Works on appetite and reward centers.
Diethylpropion & Phendimetrazine: Older stimulant-based appetite suppressants.
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3. Acid-Reducing Drugs & Digestion
Proton Pump Inhibitors (Omeprazole, Pantoprazole, Lansoprazole, Dexlansoprazole):
Evidence for weight changes is mixed; some show mild weight gain.
Long-term use can reduce absorption of B12, magnesium, calcium and alter gut microbiota, which may indirectly influence metabolism.
Hydrochloric Acid (HCl) deficiency: Leads to maldigestion and nutrient malabsorption, sometimes contributing to unintentional weight loss.
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4. Supplements That Support Weight Loss
Caffeine: Boosts metabolism and fat oxidation.
Green Tea Extract (EGCG): Modestly increases calorie burn.
L-Carnitine: Assists in fat transport into mitochondria (effects modest).
Fiber (psyllium, glucomannan): Increases satiety → reduces intake.
Capsaicin (chili extract): Small thermogenic effect.
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Conclusion
Weight Gain Drivers: Antihistamines, corticosteroids, insulin, sulfonylureas, antipsychotics, antidepressants, anabolic hormones, and specific appetite stimulants.
Mechanism: Block satiety signals, increase appetite, stimulate fat storage, or cause fluid retention.
Weight Loss Drivers: Anti-diabetic drugs (metformin, GLP-1 agonists, SGLT2 inhibitors, acarbose), appetite suppressants, fat blockers (Orlistat), and metabolic boosters (caffeine, fiber, green tea).
Mechanism: Suppress appetite, block nutrient absorption, increase calorie burn, or waste glucose through urine.