ACP names semaglutide and tirzepatide as first-line medication options

The American College of Physicians has issued its first living clinical guideline on medication for adults with overweight or obesity in outpatient care. When an eligible nonpregnant adult with obesity starts pharmacologic treatment, ACP conditionally recommends semaglutide or tirzepatide as the first options to consider along with lifestyle changes.

For adults with a BMI of at least 30, the guideline places phentermine-topiramate second, liraglutide third and naltrexone-bupropion fourth. For adults with a BMI from 27 through 30 who also have type 2 diabetes, abnormal cholesterol, high blood pressure, obstructive sleep apnea or cardiovascular disease, semaglutide and tirzepatide are again the first medication options, followed by liraglutide.

ACP rated the evidence for semaglutide and tirzepatide as moderate certainty. Its recommendations are conditional. The guideline tells clinicians and patients to discuss benefits and harms as well as cost, availability, other health conditions, treatment goals, life expectancy, preferences, contraindications and warnings. It also calls for counseling about possible nutritional deficiencies and loss of muscle or bone, especially in older adults.

The guideline is described as living because ACP plans to revise it when new evidence changes the treatment picture. That matters in a field where new drugs and longer-term results are arriving quickly.

On June 16, 2026, the American College of Physicians published a living clinical guideline in Annals of Internal Medicine conditionally recommending semaglutide and tirzepatide as first-line pharmacologic options for eligible nonpregnant adults, alongside lifestyle modification. For adults with obesity (BMI ≥30), ACP recommends semaglutide and tirzepatide as first-line drug options; for adults with overweight (BMI ≥27 to 30) and at least one comorbid condition, type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease, it recommends semaglutide or tirzepatide first-line. Phentermine-topiramate is second-line, liraglutide third-line (second-line in the overweight-with-comorbidity group), and naltrexone-bupropion fourth-line. The guideline asks clinicians to weigh benefits, harms, cost, access, contraindications, and patient preferences in shared decisions.

A "living" guideline is designed to be updated as evidence changes rather than waiting years between editions.

The guideline gives primary care a treatment order

Primary-care and internal-medicine visits may now start with a clearer order of medication options. The recommendations recognize the weight-loss evidence for semaglutide and tirzepatide while keeping the decision inside a shared discussion about safety, affordability and what the patient can realistically continue.

The ranking can also make the next step easier to discuss when the first drug is not appropriate, cannot be obtained or does not produce an adequate response. It does not eliminate alternatives. It gives clinicians a published framework for choosing among them.

This gives internists, the doctors most patients see first, a named ordering of drug options. It complements rather than repeats ACP's August position paper on coverage: this document is about prescribing, that one was about payer policy. For patients, the practical effect is more primary-care conversations that start from these two drugs and step through alternatives when they are unsuitable.

First-line does not mean mandatory

"First-line" does not mean everyone with a qualifying BMI should take one of these drugs. The recommendations apply when medication is being initiated, and they remain conditional. Pregnancy, contraindications, adverse effects, cost, supply, coverage and patient preference can change the choice.

This guideline is focused on medicines used with lifestyle changes. It does not settle whether medication or bariatric surgery is the better option for a particular person. It also does not promise insurance coverage or uninterrupted access to the recommended drug.

Conditional means exactly that: not a mandate, and not a claim these are the only reasonable choices. It does not address surgery, which ACP treated separately in its access paper, and it does not override individual factors such as prior pancreatitis, medullary thyroid cancer history, pregnancy plans, or insurance formularies.