ACP guideline names semaglutide and tirzepatide first-line for obesity

The American College of Physicians released a living clinical guideline that conditionally recommends clinicians start one of several weight-management medications along with lifestyle changes in nonpregnant adults with obesity, naming semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) as first-line options ^[1][2].

The guideline appears in Annals of Internal Medicine alongside a living systematic review and network meta-analysis and a separate cost-effectiveness review that were posted online June 16, 2026 ^[1]. It was written for internal medicine physicians and other clinicians treating adults in outpatient settings, and used the GRADE approach to rate the evidence and the strength of the recommendations ^[1][2].

What the recommendations say

For adults with obesity, defined as a body mass index of 30 kg/m2 or higher, the ACP lists semaglutide and tirzepatide as first-line treatment, each supported by moderate-certainty evidence ^[1][2]. Phentermine–topiramate is second-line (low certainty), liraglutide third-line (low certainty), and naltrexone–bupropion fourth-line (low certainty) ^[1][2].

For adults with overweight — BMI 27 to 30 — who also have type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease, semaglutide and tirzepatide are again first-line, with liraglutide second-line (low certainty) ^[1][2].

Both are conditional recommendations. When starting a medication, or switching because of an inadequate response, the guideline says clinicians and patients should discuss benefits, harms, costs, access and availability, clinical comorbidities, weight loss goals, life expectancy, values and preferences, and contraindications and warnings ^[1][2]. The examples given include monthly pregnancy tests with phentermine–topiramate, a contraindication to phentermine–topiramate in people with cardiovascular disease, and suicidal ideation with naltrexone–bupropion ^[1][2]. In the overweight group, the example cited is use in pregnancy ^[1][2].

The document states that clinical guidelines are meant to guide care based on the best available evidence, may not apply to every patient or situation, and should not replace a clinician's judgment ^[2].

Scope and context

The ACP committee evaluated many drugs, including cagrilintide–semaglutide, dulaglutide, exenatide, liraglutide, lixisenatide, naltrexone–bupropion, orforglipron, phentermine alone, phentermine–topiramate, retatrutide, semaglutide, tirzepatide, and combinations of these; SGLT-2 inhibitors and orlistat were considered and not selected ^[2]. Some investigational medications were included in anticipation of regulatory approval and future updates ^[2].

The guideline cites US data showing 68.5% of adults have overweight or obesity — 34.3% overweight and 34.2% obesity — based on self-reported figures that may underestimate obesity ^[2]. Globally it cites 59% of adults with overweight or obesity (43% overweight and 16% obesity), and a World Obesity Federation estimate that the global impact of overweight and obesity will exceed $4.3 trillion in 2035, nearly 3% of global gross domestic product ^[2].

The guideline also notes limits of BMI: it was designed to stratify population-level risk, is less sensitive for identifying excess body fat, and does not account for fat distribution or muscle mass ^[2]. For adults of South Asian, Southeast Asian, or East Asian ethnicity, overweight has been defined as a BMI of 23 to 24.9 and obesity as 25 or higher, though no consensus has been established on race-specific cutoffs ^[2].

Two committee members were recused over conflicts of interest: Paul G. Shekelle, MD, PhD, MPH, for a moderate-level conflict, and Jeffrey A. Tice, MD, who acquired a high-level conflict during development ^[1].

Why it matters for patients

Having semaglutide and tirzepatide listed first does not by itself change what an insurance plan covers, and the guideline directs that cost, access and availability be part of the conversation ^[1][2]. Because the recommendations are conditional and the document says they should not replace clinical judgment, the ranking works as a starting point for a discussion rather than a fixed rule ^[1][2].

The population covered is nonpregnant adults in outpatient settings; pregnant adults are outside it ^[1][2]. The recommendations address starting therapy, including switching after an inadequate response ^[1][2]. They make no recommendations about maintenance treatment or about stopping a drug; the published recommendations concern initiation ^[1][2].

What happens next

The ACP plans to keep the topic living because it is a priority for clinical care and an active area of research, and will weigh quantitative and qualitative factors to decide how often to update it ^[2]. No update schedule or date has been disclosed ^[2]. ACP guidelines are automatically withdrawn or invalid five years after publication, or once an update is issued ^[2]. The supporting living review and the cost-effectiveness review were posted online June 16, 2026 ^[1].