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)

Recommendation 1: in nonpregnant adults with obesity (BMI ≥30 kg/m²), initiate pharmacologic treatment with lifestyle modifications for weight management in outpatient settings. First-line: semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line: phentermine-topiramate (low-certainty evidence); third-line: liraglutide (low-certainty evidence); fourth-line: naltrexone-bupropion (low-certainty evidence).

Recommendation 2: in nonpregnant adults with overweight (BMI ≥27 to 30 kg/m²) and T2D, dyslipidemia, hypertension, obstructive sleep apnea or CVD, initiate pharmacologic treatment with lifestyle modifications for weight management. First-line: semaglutide (moderate-certainty evidence) and tirzepatide (moderate-certainty evidence); second-line: liraglutide (low-certainty evidence).

When initiating or switching for inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings (e.g., monthly pregnancy tests with phentermine-topiramate, its contraindication in CVD, suicidal ideation with naltrexone-bupropion; use in pregnancy).