Annals of internal medicineJun 15, 2026

Medication and Lifestyle Changes for Overweight or Obese Adults Outside of Pregnancy: Updated Treatment Guidelines

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 16, 2026

Abstract

The American College of Physicians recommends pharmacologic treatments for weight management in adults with obesity (body mass index ≥30 kg/m) and overweight (body mass index ≥27 to 30 kg/m) with certain comorbidities.

First-line treatments for obesity include semaglutide and tirzepatide, both supported by moderate-certainty evidence.
Second-line treatment options for obesity are phentermine-topiramate and liraglutide, with low-certainty evidence.
For overweight adults with type 2 diabetes or other specific conditions, first-line treatments are again semaglutide and tirzepatide.
Clinical discussions regarding weight management should cover benefits, harms, costs, and individual patient factors.
Considerations include potential contraindications and specific requirements, such as pregnancy tests for phentermine-topiramate.

Simplified

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: ACP suggests initiating one of the following pharmacologic treatments with lifestyle modifications for weight management in nonpregnant adults with obesity (body mass index ≥30 kg/m) 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). 2

RECOMMENDATION 2: ACP suggests initiating one of the following pharmacologic treatments with lifestyle modifications for weight management in nonpregnant adults with overweight (body mass index ≥27 to 30 kg/m) 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). 2