Snapshot A 45-year-old obese woman is seeking weight loss options. She has tried multiple diet plans without much effect. Although she considered gastric bypass surgery, she is worried about the complications of surgery as her mother died after an abdominal surgery. She had heard a commercial about a miracle weight loss drug and asks her primary care physician about her options. Her doctor warns her that while this medication can induce weight loss, it can also have other side effects such as defecation urgency and abdominal pain. Glucagon-like peptide 1 (GLP) agonists Mechanism of action bind to GLP-1 receptors to cause glucose-dependent insulin release from pancreatic islet cells Clinical use type 2 diabetes obesity (considered first-line for weight loss) Adverse effects nausea vomiting diarrhea gastrointestinal effects tend to improve over time Orlistat Mechanism of action reversibly inhibits pancreatic lipase, causing decreased breakdown and absorption of fats causes a caloric deficit Clinical use obesity weight loss Adverse effects gastrointestinal upset flatulence frequent bowel movements defecation urgency anal discharge fat-soluble vitamin deficiencies Phentermine-topiramate Mechanism of action Phentermine acts as a sympathomimetic, which suppresses appetite and increases metabolic activity Mechanism of topiramate for weight loss is unknown Clinical use obesity Contraindications pregnancy known cardiovascular disease, including hypertension Adverse effects dry mouth constipation paresthesias psychiatric symptoms Bupropion-naltrexone Mechanism of action Stimulates pro-opiomelanocortin cells to suppress appetite and increase energy expenditure Clinical use obesity, especially in patients with comorbid smoking who wish to quit Contraindications pregnancy severe alcohol use disorder at risk of withdrawal seizures seizure disorders bupropion lowers the seizure threshold eating disorders Adverse effects nausea vomiting constipation insomnia headache Lorcaserin Removed from the market due to increased risk of cancer Mechanism of action selective serotonin receptor agonist (5-HT(2C) agonist) results in decreased food intake via increasing sensation of satiety Clinical use obesity in the presence of weight-related comorbidity Adverse effects gastrointestinal upset dizziness pharyngitis fatigue