Nearly two decades after its last major update on pharmaceutical weight management, the American College of Physicians (ACP) is shifting its clinical guidance for treating obesity.

In new recommendations, the organization positions high-efficacy GLP-1 agonists — specifically semaglutide (Wegovy) and tirzepatide (Zepbound) — as the first-line pharmaceutical standard for adults with a BMI of 30 or higher, reflecting recent advances in obesity drugs since the organization last issued its policy over two decades ago. The ACP guidelines include separate guidelines for treating overweight.

“Knowing how effective the medications are, [the obesity medicine community] can certainly recommend medication in addition to lifestyle changes,” said Juliana Simonetti, MD, an obesity medicine specialist and co-director of the Comprehensive Weight Management Program at the University of Utah in Salt Lake City, who was not involved in the ACP update. 

The ACP’s guidance largely follows protocols released last summer from the American College of Cardiology, which also recommends clinicians prescribe semaglutide and tirzepatide.

The group recommends phentermine and topiramate (Qsymia) plus lifestyle modifications as second-line treatments, citing weaker evidence for efficacy compared with first-line recommendations. Liraglutide and naltrexone-bupropion are recommended as third- and fourth-line recommendations, respectively, for obesity. 

“Lifestyle modifications are still the first-line treatment, and we also have these medications available that do have benefits. And at this point, the evidence shows that these benefits outweigh the potential harms,” said Amir Qaseem, MD, PhD, chief science officer of ACP.

The organization says that if an adult becomes pregnant while taking any of the drugs, treatment should be discontinued. Adults using phentermine-topiramate who can become pregnant should undergo monthly pregnancy tests to monitor if they need to discontinue treatment.

The recommendations apply to patients who have already tried lifestyle changes without desired results and have not undergone weight-loss surgeries.

Pharmacologic Approaches Also Recommended for Overweight 

The ACP has published separate recommendations for people with overweight. Although the CDC defines overweight as a BMI between 25 and 29.9, the ACP has used a BMI of at least 27 as the lower threshold, based on available research. 

These patients should also have at least one obesity-related comorbidity to qualify for the drugs, such as dyslipidemia, hypertension, obstructive sleep apnea, or cardiovascular disease.

Semaglutide and tirzepatide are first-line pharmacologic approaches, but liraglutide is recommended as a second-line treatment based on the strongest evidence in people with overweight, instead of phentermine and topiramate. 

Clinicians should still write prescriptions based on patient preferences and health concerns, Simonetti said.

“Having more treatment options really helps us, but if someone doesn’t need to lose a lot of weight, maybe we can use the older generation drugs,” Simonetti said. “But if they have inflammatory issues, maybe a GLP-1 would make more sense.”

For patients with either overweight or obesity, Simonetti said she considers comorbidities. For instance, tirzepatide may be the best choice for someone with co-occurring sleep apnea, based on clinical data showing the drug can improve outcomes for these patients. For someone with a history of stroke, Simonetti would be more apt to prescribe semaglutide, which studies have shown can reduce the risk for major adverse cardiovascular events in adults with overweight or obesity by as much as 20%.

A Living Document

ACP will update the guidelines as more data on safety, efficacy, and management of existing and new drugs are released, Qaseem said.

“There are already some [new drugs] that will likely be coming out early next year,” such as sitagliptin, a dipeptidyl peptidase-4 inhibitor, he said.

Clinicians also need more evidence for prescribing maintenance doses, Qaseem said. Up to 65% of people discontinue GLP-1 drugs within the first year of taking them and usually return to their original weight within 2 years. Data on long-term use are also lacking, he said.

Clinicians should help patients develop long-lasting changes in diet and exercise to prevent weight regain. But some patients may need to be on medications for longer, potentially at lower doses, he said.

“We still need to figure out what the optimal duration of treatment is; we do know that when people stop these medications, weight regain does occur,” Qaseem said.

The BMI Issue

Simonetti and Qaseem said the use of BMI alone to diagnose overweight and obesity is outdated and called for a more nuanced approach.

“There are other measures that seem to be more accurate in assessing risk,” Simonetti said. “We need to take into account waist circumference, weight-to-height ratio.”

While the guidance does not approach this issue, the recommendations point out racial and ethnic differences in BMI that should influence care. While a BMI of at least 25 is considered overweight in White, Black, and Hispanic people, Asian adults who have a BMI of at least 23 are considered to have overweight.

“We need to keep that in mind, and we need more data that is race- or ethnicity-specific,” Qaseem said. “Do we take a different approach [with people of different races or ethnicities]?”

Qaseem and Simonetti reported no relevant financial disclosures.

Kaitlin Sullivan is a journalist living in Colorado.