Table 1.

Currently available obesity medications [35−40]

Medication	Orlistat (Xenical® 120 mg; Alli® 60 mg)	Phentermine (Duromine® Metermine®)	Phentermine-topiramate ER (Qsymia®)	Naltrexone-Bupropion (Contrave® Mysimba®)	Liraglutide 3 mg (Saxenda®)	Semaglutide 2.4 mg (Wegovy®)
Regulatory approval	FDA, EMA, Australia Central and South America	FDA, Australia	FDA	FDA, EMA, Australia, Central and South America	FDA, EMA, Australia, Central and South America	FDA, EMA, Australia
Dosage form and dosing	60-120 mg three times a day, with meals, oral	15, 30, 37.5 (or 40) mg once daily, oral	Up to 15 mg phentermine–92 mg topiramate once daily, oral	16 mg naltrexone–180 mg bupropion twice a day, oral	3 mg, once daily, subcutaneous	2.4 mg once weekly, subcutaneous
Mechanism of action	Inactivation of gastric and pancreatic lipase	Stimulation of the release of noradrenaline, serotonin, and dopamine	Sympathomimetic and GABA receptor activation, carbonic anhydrase inhibition	Opioid receptor antagonist; dopamine and noradrenaline reuptake inhibitor	Central control of appetite and peripheral effects through GLP-1 receptor agonism in hypothalamus and hindbrain; also slows gastrointestinal transit and enhances glucose metabolism

Key indications	BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with at least one weight-related health condition
	>12 years of age*	>16 years of age*	>12 years of age*	>18 years of age*	>12 years of age*	>12 years of age*
Average placebo-subtracted weight loss at ~12 months (%)*	4% at 1 year (120 mg tds) [30]	6% at 20 weeks [31]	9% at 1 year [32]	5% at 1 year [33]	6% at 1 year [34]	12.5% at 68 weeks [35]
Proportion of participants with 5% and 10% weight loss at ~12 months*	73 and 41% (vs 45 and 21% with placebo)	Not reported	67 and 47% (vs 17 and 7% with placebo)	48 and 25% (vs 16 and 7% with placebo)	63 and 33% (vs 27 and 11% with placebo)	86 and 69% (vs 31 and 12% with placebo)
Contraindications	Pregnancy, lactation	Coronary artery disease, uncontrolled hypertension, cardiac arrhythmias, hyperthyroidism, glaucoma, MAOI, not recommended with SSRI, pregnancy, lactation	As for phentermine, plus glaucoma, history of renal stones, hyperthyroidism and within 14 days of treatment with monoamine oxidase inhibitors, pregnancy, lactation	Uncontrolled hypertension, seizure disorders, bipolar disorder, undergoing abrupt discontinuation of alcohol or anti-convulsant drugs, chronic opioid use, MAOI, pregnancy, lactation	Personal or family history of medullary thyroid carcinoma or MEN 2, pregnancy, lactation	As for liraglutide
Adverse effects	Steatorrhea, oily spotting, faecal urgency, fat-soluble vitamin deficiency	Dry mouth, insomnia, palpitations, tachycardia, hypertension, anxiety, dizziness, small risk of primary pulmonary hypertension	As for phentermine, plus paraesthesia, dysgeusia (altered taste), memory loss, depression, fetal abnormalities	Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhoea, hypertension, seizures, precipitation of mania	Nausea, diarrhea, constipation, vomiting, headache, dyspepsia, abdominal pain	As for liraglutide

(modified from Perdomo et al. [32] Lancet 2023;401:1116-30)

EMA European Medicines Agency, FDA Food and Drug Administration, GABA gamma-aminobutyric acid, MAOI monoamine oxidase inhibitor, MEN 2 Multiple endocrine neoplasia type 2, SSRI Selective serotonin reuptake inhibitors, T2D Type 2 diabetes

*indicates FDA age approval