Physiopathology and Treatment of Obesity and Overweight: A Proposal for a New Anorectic

Table 2

Mechanism of action and main side effects of FDA-approved antiobesity medications for long-term​ use.

Drug	Mechanism of action	Adverse events
Bupropion-naltrexone	Opioid receptor antagonist	Nausea, constipation, headache, vomiting, dizziness, dry mouth, diarrhea, sleep disorder
	DA and NE reuptake inhibitor
Liraglutide	GLP-1 analog	Increased heart rate, hypoglycemia, constipation, diarrhea, nausea, vomiting, headache
Orlistat	Gastric and pancreatic lipase inhibitor	Oily rectal leakage, abdominal distress and pain, flatulence with discharge, fecal urgency and incontinence, steatorrhea
Phentermine-topiramate	NE agonist/GABA agonist glutamate antagonist	Elevation in heart rate, mood and sleep disorders, cognitive impairment, metabolic acidosis, paresthesia, dry mouth
Semaglutide	GLP-1 analog	Nausea, vomiting, diarrhea, abdominal pain, constipation, headache
Setmelanotide	MC4R agonist	Injection site reactions, hyperpigmentation, nausea, headache, diarrhea, vomiting, abdominal pain
Tirzepatide	GIP/GLP-1 dual agonist	Nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, abdominal pain

DA, dopamine; GABA, gamma-aminobutyric acid; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide 1; MC4R: melanocortin-4 receptor; NE, norepinephrine. Only for people aged 6 and older who have obesity due to inherited conditions: (i) pro-opiomelanocortin deficiency; (ii) proprotein subtilisin-kexin type 1 deficiency; (iii) leptin receptor deficiency.