ACP Suggests First-Line Obesity Drugs
Semaglutide and tirzepatide had the greatest net benefit among evaluated treatments, the committee concluded.
By
Kathryn Wighton
June 16, 2026
Clinical Scorecard: ACP Suggests First-Line Obesity Drugs
At a Glance
Category Detail
Condition Obesity and overweight with weight-related comorbidities Key Mechanisms Semaglutide and tirzepatide as first-line treatments; lifestyle modifications included. Target Population Nonpregnant adult patients with obesity (BMI ≥ 30 kg/m²) or overweight (BMI 27-<30 kg/m²) with comorbidities. Care Setting Outpatient management
Key Highlights
Semaglutide and tirzepatide recommended as first-line treatments based on moderate-certainty evidence. Phentermine-topiramate, liraglutide, and naltrexone-bupropion recommended as second to fourth-line treatments based on lower-certainty evidence. Both semaglutide and tirzepatide improved weight-loss outcomes and hemoglobin A1c. Phentermine-topiramate is suggested only for nonpregnant adults without established cardiovascular disease. All medications carry specific warnings and potential adverse effects. Guideline-Based Recommendations
Diagnosis
Obesity defined as BMI ≥ 30 kg/m². Overweight defined as BMI 27-<30 kg/m² with weight-related comorbidities. Management
First-line: Semaglutide and tirzepatide. Second-line: Phentermine-topiramate for obesity; liraglutide for overweight with comorbidities. Third-line: Liraglutide. Fourth-line: Naltrexone-bupropion. Monitoring & Follow-up
Monitor for weight loss, hemoglobin A1c, and adverse events. Risks
Potential thyroid C-cell tumor risk with semaglutide, tirzepatide, and liraglutide. Teratogenic risk with phentermine-topiramate. Patient & Prescribing Data
Adults with obesity or overweight and weight-related comorbidities.
Discuss benefits, harms, costs, access, and contraindications before initiating treatment.
Clinical Best Practices
Use lifestyle modifications alongside pharmacologic treatments. Consider patient-specific factors such as comorbidities and preferences. Related Resources & Content
