Pharmacologic Treatments With Lifestyle Modifications in Nonpregnant Adults With Overweight or Obesity in Outpatient Settings: A Living Clinical Guideline From the American College of Physicians (April 2026)

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline for internal medicine physicians and other clinicians caring in outpatient settings for adults with overweight or obesity. METHODS: This guideline is based on systematic reviews of pharmacologic treatments in adults with overweight or obesity and used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RECOMMENDATION 1: ) in outpatient settings (conditional recommendation): First-line treatments are semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line treatment is phentermine-topiramate (low-certainty evidence); third-line treatment is liraglutide (low-certainty evidence); fourth-line treatment is naltrexone-bupropion (low-certainty evidence). When initiating a recommended medication for weight management or switching to another recommended medication because of an inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, clinical comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings (for example, the requirement for monthly pregnancy tests with use of phentermine-topiramate, the contraindication to phentermine-topiramate in those with cardiovascular disease, and suicidal ideation with naltrexone-bupropion). RECOMMENDATION 2: ) and type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease (conditional recommendation): First-line treatments are semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line treatment is liraglutide (low-certainty evidence). When initiating a recommended medication for weight management or switching to another recommended medication because of an inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, clinical comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings (for example, use in pregnancy).