New ACP guideline puts GLP-1/GIP drugs first for obesity care

Clinical Takeaway: Start with semaglutide or tirzepatide plus lifestyle modification for most eligible adults with obesity or high-risk overweight, and individualize selection based on benefits, harms, cost, and patient goals.

The American College of Physicians (ACP) has issued a new living clinical guideline that reshapes pharmacologic management of overweight and obesity in nonpregnant adults, placing incretin-based therapies at the forefront. The recommendations emphasize combining medications with lifestyle interventions—improved nutrition and physical activity—and tailoring choices through shared decision-making.

For adults with obesity (BMI ≥30 kg/m²), ACP recommends semaglutide and tirzepatide as first-line pharmacologic options. Phentermine–topiramate is suggested as second-line therapy, liraglutide as third-line, and naltrexone–bupropion as fourth-line.

For adults with overweight (BMI ≥27 to <30 kg/m²) who have at least one weight-related comorbidity—such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease—ACP again prioritizes semaglutide or tirzepatide as first-line therapy, followed by liraglutide as second-line.

The recommendations reflect robust evidence from a companion network meta-analysis showing the greatest and most sustained weight loss with semaglutide and tirzepatide compared with older agents. ACP underscores that medication choice should not be automatic: clinicians and patients should weigh effectiveness against adverse effects, costs, access, contraindications, and patient preferences.

The guideline also calls attention to potential harms associated with weight loss therapies. Clinicians are advised to monitor for gastrointestinal effects and to counsel patients about unintended consequences such as nutritional deficiencies as well as loss of lean mass and bone density—especially in older adults.

“This is an area of rapid change, and clinicians need up-to-date, evidence-based guidance on how best to use these medications,” the authors note, emphasizing the importance of individualized care alongside evolving evidence.

Because the guideline is “living,” ACP will update recommendations as new data emerge, particularly given the fast-moving landscape of anti-obesity pharmacotherapy.

Overall, the message is clear: newer GLP-1–based and dual incretin therapies now lead treatment pathways, but successful weight management still depends on pairing pharmacologic therapy with sustained lifestyle modification and ongoing clinical oversight.

Sources:

Qaseem A, et al. (2026, June 15). Ann Intern Med. 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

Qaseem A, et al. (2026). Ann Intern Med. Benefits and harms of pharmacologic treatments in adults with overweight or obesity: A living systematic review and network meta-analysis for the American College of Physicians