American College of Physicians issues a living guideline on obesity pharmacotherapy

The American College of Physicians (ACP) has published a living clinical guideline in Annals of Internal Medicine that conditionally suggests clinicians start one of several weight-management medications, together with lifestyle changes, in nonpregnant adults with obesity. Semaglutide and tirzepatide are named as first-line options, both backed by moderate-certainty evidence ^[1][2].

What the guideline says

Recommendation 1 applies to nonpregnant adults with obesity, defined as a body mass index of 30 kg/m2 or higher, treated in outpatient settings. ACP ranks the options in tiers: semaglutide (sold as Ozempic, Wegovy and Rybelsus) and tirzepatide (Mounjaro and Zepbound) are first-line, both with moderate-certainty evidence; phentermine–topiramate is second-line (low-certainty evidence); liraglutide is third-line (low-certainty); and naltrexone–bupropion is fourth-line (low-certainty) ^[1][2].

Recommendation 2 covers nonpregnant adults with overweight, defined as a BMI of 27 to 30 kg/m2, who also have type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea or cardiovascular disease. Here, semaglutide and tirzepatide are again first-line with moderate-certainty evidence, and liraglutide is second-line with low-certainty evidence ^[1][2].

Both recommendations are "conditional," ACP's weaker category, and both were developed using the GRADE system for rating evidence certainty and recommendation strength ^[2]. The guideline says that when starting a medication or switching because of an inadequate response, clinicians and patients should discuss benefits, harms, costs, access and availability, other health conditions, weight loss goals, life expectancy, values and preferences, and contraindications and warnings. It gives examples: the requirement for monthly pregnancy tests with phentermine–topiramate, the contraindication to phentermine–topiramate in people with cardiovascular disease, and suicidal ideation with naltrexone–bupropion ^[1][2].

What was and wasn't evaluated

ACP's committee reviewed a broad list of drugs: cagrilintide–semaglutide, dulaglutide, exenatide, liraglutide, lixisenatide, naltrexone–bupropion, orforglipron (Foundayo), phentermine alone, phentermine–topiramate, retatrutide, semaglutide, tirzepatide, and combinations of these with or without lifestyle programs. Some investigational medicines were included "in anticipation of regulatory approval and for future updates" ^[2]. Even so, only the drugs listed in the two recommendations were given a tier. SGLT2 inhibitors and orlistat were identified but not selected for review ^[2].

The guideline frames lifestyle modification — nutrition and physical activity — as first-line management, with drugs added when lifestyle changes alone do not produce adequate weight loss or maintenance ^[2]. It also notes BMI's limits: it was designed to stratify population-level risk and does not account well for body fat distribution or muscle mass, and no consensus exists on race- and ethnicity-specific cutoffs ^[2].

For context, ACP cites self-reported data showing 68.5% of US adults have overweight or obesity, split roughly evenly at 34.3% overweight and 34.2% obesity, and says these figures may understate true prevalence. Globally, the World Obesity Federation estimate cited puts the combined economic impact above $4.3 trillion in 2035, close to 3% of global gross domestic product ^[2].

Why it matters for patients

Guidelines from a large physician organization influence how primary care doctors prescribe and, over time, how insurers write coverage rules. Putting semaglutide and tirzepatide at the top tier, with moderate-certainty evidence, gives clinicians a citable basis for starting a GLP-1 drug rather than an older option first.

The "conditional" label matters too. In GRADE, a conditional recommendation signals that the balance of benefits, harms and costs is close enough that different informed patients may reasonably choose differently — which is why ACP built an explicit discussion checklist into both recommendations ^[1][2]. ACP also acknowledges that patients remain undertreated, likely because of availability and access problems ^[2].

The published abstract does not list average weight-loss percentages, cardiovascular outcomes or head-to-head differences between semaglutide and tirzepatide; those sit in the companion systematic reviews and are not stated in the material reviewed here ^[1][2].

What happens next

The guideline and its companion reviews were posted online 16 June 2026, with print publication in the August 2026 issue of Annals of Internal Medicine (volume 179, issue 8) ^[1]. ACP says it plans to maintain the topic as "living" because it is a priority area with active research, and that its committee will weigh quantitative and qualitative factors to decide how often to update — no fixed schedule has been announced ^[2]. Under ACP policy, guidelines are automatically withdrawn five years after publication or once an update is issued ^[2].

Two committee members were recused over conflicts of interest: Paul G. Shekelle for a moderate-level conflict, and Jeffrey A. Tice, who acquired a high-level conflict during development and was removed from further discussion, authorship and voting ^[1].