Oral weight-loss pills may be on their way

New weight-loss drugs mimic a hormone called glucagon-like peptide-1 (GLP-1) to target areas of the brain that regulate appetite and food intake. 

Semaglutide, a drug manufactured by Novo Nordisk, is available in two forms: Ozempic, a diabetes treatment, and Wegovy, a higher dose of the drug approved for weight loss. Separately, Eli Lilly manufactures tirzepatide. So far, tirzepatide has only been approved under the brand name Mounjaro to treat diabetes, but Lilly is in the process of getting the drug approved for obesity.

Currently, these drugs are only available as weekly injections, but manufacturers are working to develop oral versions — with some already reporting promising results from clinical trials.

In May, Novo Nordisk released the results of a Phase 3 clinical trial for a daily oral form of semaglutide. In the trial, which included 667 adults diagnosed as overweight or obese, participants who received the oral treatment lost 15.1% of their body weight over 68 weeks. Meanwhile, those who received a placebo only lost 2.4% of their body weight.

Overall, 85% of participants who took semaglutide lost at least 5% of their body weight during the study period, compared to only 26% of participants who received the placebo.

In a separate trial, Novo Nordisk also evaluated oral semaglutide in over 1,600 individuals with type 2 diabetes. The participants were divided into three groups and give different doses of the drugs (14-mg, 25-mg, or 50-mg). The researchers found that those who took the 25-mg or 50-mg doses lost more weight and had larger reductions in blood sugar compared to those who took the lowest dose.

Eli Lilly also recently reported results of a mid-stage clinical trial evaluating the efficacy of a non-peptide GLP-1 drug called orforglipron. In the trial, which included over 270 patients with obesity, participants who took the drug lost up to 14.7% of their body weight over 36 weeks.

According to Lilly, it is currently working on a larger, late-stage clinical trial of orforglipron, and hopes to generate sufficient evidence for regulatory approval in the future.

Commentary

According to Scott Hagan, an assistant professor of medicine at the University of Washington, oral forms of weight-loss drugs increase patients' access to them since swallowing a pill is typically easier for many people than injecting a drug.

"It's a welcome addition to treatment options for patients who may benefit from weight management," Hagan said.

Analysts also suggest that the oral versions of the weight-loss drugs will be more affordable than the injectable versions. By some estimates, oral forms of weight-loss drugs could cost around $500 a month by 2026 — roughly half the current cost of the injected drugs — and the price could decrease to around $350 a month by 2030.

"If these oral medications are more affordable or more accessible, that could be where they could fill that gap," said Ania Jastreboff, director of the Yale Obesity Research Center.

However, as these weight-loss drugs have become more popular, some experts have expressed concerns about how they will impact people's body image and diet culture overall.

"Any time there are medications for weight loss, we know that is a tool that people can use for a disordered eating reason," said A. Janet Tomiyama, a professor of psychology at the University of California, Los Angeles.

According to Hagan, clinicians should consider whether these weight-loss drugs can help patients be healthier rather than just helping them lose weight. "I am concerned about these medications being broadly used just to promote weight loss, and how it contributes to our general diet culture, our cultural obsession with thinness," he said. (Loftus, Wall Street Journal, 6/25; Blum, New York Times, 6/25)

Demand — and concern — is growing for the newest generation of weight loss drugs, and leaders have many questions about protocol, supply, and coverage of these drugs, as well as the consequences of patients using them for their unintended purpose. Radio Advisory's Rachel Woods walked through these questions with experts Kara Marlatt, Gaby Marmolejos, and Chloe Bakst and discussed the potential future of weight management in U.S. healthcare. Read a lightly edited excerpt from the interview below and listen to the episode for the full conversation.