ACP Clinical Guideline on Treatments of Overweight or Obese Adults Save

Know-it-now

• Semaglutide and tirzepatide are ACP's first-line pharmacologic agents for both obesity (BMI ≥30) and overweight-with-comorbidity (BMI 27–<30) categories, based on moderate-certainty evidence.
• The guideline lists four clear choices for obesity management (semaglutide/tirzepatide → phentermine-topiramate → liraglutide → naltrexone-bupropion)
• The preferred options for overweight-plus-comorbidity patients are semaglutide or tirzepatide; and then, liraglutide.
• ACP anticipates and plans for iterative updates. This is a “living” document with current recommendations that are provisional, rather than fixed.
• ACP mandates counseling on musculoskeletal harms of pharmacologic weight loss, especially significant muscle and bone density loss (especially in older adults).
• Pharmacotherapy is explicitly adjunctive to, not a substitute for, lifestyle modification (nutrition and physical activity), and treatment decisions should be individualized through shared decision-making.

The American College of Physicians (ACP) in July 2026 published its first living clinical guideline addressing pharmacologic management of overweight and obesity in nonpregnant adults in outpatient settings. As this therapeutic area is rapidly changing, ACP intends to update recommendations continuously over time. 

The guidelines importance is driven by striking epidemiology: 59% of the global population and 68.5% of US adults now have overweight or obesity. These disorders are chronic and progressive, significantly driving elevated risks for type 2 diabetes, hypertension, cardiovascular disease, certain cancers and musculoskeletal disorders.

Recommendations were developed by the ACP Clinical Guidelines Committee (CGC) and Topic Expert Panel (including 13 internists & specialists and 2 nonphysician public members) using systematic reviews of pharmacologic trials and the GRADE evidence framework formulating their recommendations.

ACP Recommendation 1: For adults with obesity (BMI ≥30 kg/m²): ACP conditionally recommends initiating pharmacotherapy alongside lifestyle modification, with a clear first-line tier of semaglutide and tirzepatide (both moderate-certainty evidence). Phentermine-topiramate is designated second-line (low-certainty evidence), liraglutide third-line (low-certainty evidence), and naltrexone-bupropion fourth-line (low-certainty evidence).

ACP Recommendation 2: For adults with overweight (BMI 27–<30 kg/m²) plus at least one weight-related comorbidity (type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease): semaglutide or tirzepatide are again first-line, with liraglutide as second-line — a notably narrower tiered pathway than for the obesity category, reflecting a more selective, comorbidity-anchored indication rather than BMI alone.

Shared decision-making emphasis. ACP is explicit that initiating or switching therapy (e.g., for inadequate response) should involve structured discussion of benefits, harms, cost, access/availability, comorbidities, weight-loss goals, life expectancy, patient values/preferences, and contraindications — a framework that discourages algorithmic prescribing in favor of individualized risk-benefit calculus.

Safety counseling requirement. Notably, ACP specifically flags that physicians should counsel patients about unintended consequences of pharmacologic weight loss — nutritional deficiencies and loss of muscle and bone density — with particular emphasis in older adults. This is a directly relevant caveat for rheumatologists, given overlapping concerns about sarcopenia, osteoporosis, and fracture risk in an aging population increasingly prescribed GLP-1/GIP agents, sometimes alongside inflammatory arthritis therapies affecting bone health.

Positioning relative to lifestyle intervention. ACP is careful to state that nutrition and physical activity remain first-line management overall; pharmacotherapy is framed as an adjunct for patients whose lifestyle modification alone doesn't achieve clinically meaningful or sustained weight loss — not a replacement for it.

“The ACP CGC did not develop recommendations for cagrilintide–semaglutide, dulaglutide, exenatide, lixisenatide, orforglipron, phentermine monotherapy, or retatrutide. The ACP CGC determined that these treatments had data insufficient for decision making (dulaglutide, exenatide, and phentermine monotherapy), had been withdrawn from the market (lixisenatide), or were still investigational at the time of guideline development (cagrilintide–semaglutide, orforglipron, and retatrutide)”.