Table 2.

Overview of FDA-approved and key emerging pharmacotherapies for chronic weight management in adults

Medication Class	Agent(s)	Mechanism of Action	Typical Placebo-Subtracted Weight Loss (%)	Key Common Adverse Events	Important Considerations/Contraindications	Representative Citations
Lipase Inhibitor	Orlistat	Inhibits gastric and pancreatic lipases, reducing dietary fat absorption by ~ 30%	3–5%	GI: Steatorrhea, oily spotting, fecal urgency	Malabsorption of fat-soluble vitamins; caution with history of kidney stones (oxalate nephropathy), cholestasis.	[54]
GLP-1 Receptor Agonist	Liraglutide 3.0 mg	Activates GLP-1 receptors; increases satiety, slows gastric emptying, enhances glucose-dependent insulin secretion	4–6%	GI: Nausea, vomiting, diarrhea, constipation	Risk of pancreatitis, gallbladder disease; Boxed warning: thyroid C-cell tumors (rodents); contraindicated in MTC/MEN2 history.	[55–57]
GLP-1 Receptor Agonist	Semaglutide 2.4 mg	Activates GLP-1 receptors (as above)	12–15%	GI: Nausea, vomiting, diarrhea, constipation	As above for Liraglutide. Cardiovascular benefits in patients with CVD and obesity.	[58, 59]
Dual GLP-1/GIP Receptor Agonist	Tirzepatide	Activates both GLP-1 and GIP receptors	18–21%	GI: Nausea, vomiting, diarrhea, constipation	As above for GLP-1 RAs (pancreatitis, gallbladder, thyroid C-cell tumor warning).	[45, 60]
Opioid Antagonist/Antidepressant	Naltrexone ER/Bupropion ER	Affects hypothalamic appetite pathways and brain reward systems	4–5% (RCTs); ~4% (real-world at 6mo)	Nausea, constipation, headache, vomiting, insomnia, dizziness	Boxed warning: suicidal thoughts/behaviors (bupropion); ↑BP/HR; contraindicated in uncontrolled HTN, seizures, MAOI use, opioid use, eating disorders. CV safety ongoing.	[61–65]
Sympathomimetic/Anticonvulsant	Phentermine/Topiramate ER	Phentermine suppresses appetite; topiramate enhances satiety (multiple mechanisms)	7–10%	Paresthesia, dry mouth, constipation, insomnia, dizziness	↑HR; Topiramate risks: metabolic acidosis, kidney stones, glaucoma, cognitive effects; Category X (teratogenic - oral clefts); taper on discontinuation.	[59, 66–69]
Emerging: Oral GLP-1 RA	Orforglipron	Oral non-peptide GLP-1 receptor agonist	~ 8–15% (Phase 2/3 data)	GI: Nausea, vomiting, diarrhea (similar to injectables) Potential for thyroid C-cell tumors (class effect). Full Phase 3 for obesity pending.		[70, 71]
Emerging: GLP1/GIP/Glucagon RA	Retatrutide	Activates GLP-1, GIP, and glucagon receptors	Up to ~ 22–24% (Phase 2 data)	GI: Nausea, vomiting, diarrhea (similar to incretins) Potential for thyroid C-cell tumors (class effect). Phase 3 ongoing.		[72, 73]
Emerging: Amylin/GLP-1 RA Combo	Cagrilintide + Semaglutide	Combines amylin analogue (satiety) and GLP-1 RA effects	~ 16–23% (Phase 3 data)	GI: Nausea, vomiting, diarrhea (similar to GLP-1 RAs) Potential for thyroid C-cell tumors (semaglutide component). Regulatory filing planned.		[74, 75]

Weight loss percentages are approximate mean values from key clinical trials or reviews, typically representing additional weight loss compared to placebo over 1 to 1.5 years, unless otherwise specified. Individual results may vary

ER = Extended Release; GI = Gastrointestinal; GLP−1 RA = Glucagon−like Peptide−1 Receptor Agonist; GIP = Glucose−dependent Insulinotropic Polypeptide; MTC = Medullary Thyroid Carcinoma; MEN2 = Multiple Endocrine Neoplasia syndrome type 2; BP = Blood Pressure; HR = Heart Rate; HTN = Hypertension; MAOI = Monoamine−Oxidase Inhibitor; CVD = Cardiovascular Disease

Emerging agents are investigational and not yet FDA−approved for obesity; efficacy and safety data are based on reported trial results and may evolve

All AOMs should be used as an adjunct to a reduced−calorie diet and increased physical activity