Weight Loss Medications for Adults with Obesity

Pharmacological Interventions

The American Gastroenterological Association notes that phentermine is an adrenergic agonist that promotes weight loss by activating the sympathetic nervous system, decreasing food intake and increasing resting energy expenditure 1
The American College of Cardiology recommends semaglutide, a GLP-1 receptor agonist, as a first-line option for weight loss due to its superior efficacy, with a weight loss of 14.9% from baseline 2
The combination of phentermine with topiramate extended-release leads to additive weight loss by targeting different pathways simultaneously, resulting in a weight loss of 9.8% at 15/92 mg dose after one year 3
Orlistat works by inhibiting gastrointestinal lipases, blocking absorption of about 30% of ingested fat, and is available as prescription or over-the-counter, with a weight loss of 5.8% of initial weight compared to 3.0% with placebo 3

The American Diabetes Association suggests that exercise improves insulin sensitivity and is important for long-term maintenance of weight loss, though it has only a modest effect on weight by itself 5
Behavioral approaches, including self-monitoring of food intake and exercise, nutrition education, and stimulus control, should be incorporated into a comprehensive weight management plan 5

The treatment algorithm recommends a GLP-1 receptor agonist, such as semaglutide, as the first-line option, with a target weight loss of ≥5% after 12 weeks 2
Phentermine/topiramate ER is recommended as a second-line option, with a starting dose of 3.75/23 mg and titration to 7.5/46 mg after 2 weeks 3
Orlistat is recommended as a third-line option, particularly for patients with cardiovascular concerns or contraindications to stimulants, with a recommendation for a balanced diet with no more than 30% of calories from fat 3
Regular follow-up within 2-4 weeks to assess response to interventions is essential, with consideration of bariatric surgery for patients with BMI ≥40 kg/m² or BMI ≥35 kg/m² with obesity-related complications if pharmacotherapy is unsuccessful 6