Objective:

To provide guidance on pharmacologic treatment options for weight management in nonpregnant adult patients with obesity and selected patients with overweight and weight-related comorbidities.

Approach:

• Guideline Development: Developed by the American College of Physicians (ACP) Clinical Guidelines Committee based on systematic reviews of pharmacologic treatments and using the Grading of Recommendations Assessment, Development, and Evaluation approach.
• Evidence Review: Systematic review evaluated randomized controlled trials published in English through October 2025, focusing on various health outcomes related to obesity treatments.

Key Findings:

• Semaglutide and tirzepatide are conditionally suggested as first-line treatments for nonpregnant patients with obesity.
• Phentermine-topiramate is suggested as a second-line option, liraglutide as third-line, and naltrexone-bupropion as fourth-line treatment.
• For patients with overweight and weight-related comorbidities, semaglutide and tirzepatide are also conditionally suggested as first-line treatments.
• Evidence showed semaglutide reduced all-cause mortality and major adverse cardiovascular events compared to lifestyle modifications alone.
• Tirzepatide improved weight loss and health-related quality of life compared to semaglutide but showed low-certainty evidence for all-cause mortality and major adverse cardiovascular events.

Interpretation:

The guideline discusses the need for clinicians to consider various factors such as benefits, harms, costs, and individual preferences when discussing treatment options with patients.

Limitations:

• Evidence was largely based on studies enrolling patients with class 2 obesity.
• No studies used waist or hip circumference as primary inclusion criteria.

Conclusion:

The ACP plans to maintain the guideline as a living document, updating it as new evidence becomes available.

Sources:

• Annals of Internal Medicine