oral incretin therapy

The clinical challenge of obesity treatment has long been the volatility of weight maintenance. While high-dose injectable incretin therapies can drive rapid initial weight loss, the transition to a sustainable long-term regimen often triggers a biological rebound. Data released by Eli Lilly and Company (NYSE: LLY) this Tuesday indicates that both an oral alternative and a reduced injectable dose can stabilize patients after they have reached their maximum tolerated dose (MTD).

The results from the SURMOUNT-MAINTAIN and ATTAIN-MAINTAIN trials were presented at the 33rd European Congress on Obesity (ECO) and published in The Lancet and Nature Medicine. The trials focused on whether patients could move away from the highest doses of injectable therapy without experiencing the significant weight regain that typically follows treatment interruption.

Weight Maintenance Metrics in ATTAIN and SURMOUNT

The trial data reveals a hierarchy of efficacy depending on the starting medication and the maintenance path chosen. In the ATTAIN-MAINTAIN trial, participants who transitioned from a maximum tolerated dose of Wegovy (semaglutide) to the oral medication Foundayo showed remarkable stability, maintaining all but 0.9 kg of their previously achieved weight loss on average after one year.

The results differed when participants transitioned from Zepbound MTD. In both ATTAIN-MAINTAIN and SURMOUNT-MAINTAIN, those who switched from Zepbound MTD to Foundayo maintained all but 5.0 kg of their previous weight loss on average after one year. Similarly, participants in SURMOUNT-MAINTAIN who reduced their Zepbound dose to 5 mg maintained all but 5.6 kg of their previous weight loss over the same period.

For those who remained on the maximum tolerated dose of Zepbound for an additional year in the SURMOUNT-MAINTAIN trial, the results were the most stable; these participants maintained all of their prior weight loss on average. This establishes a baseline that confirms the efficacy of the MTD for maintenance, while the Foundayo and 5 mg Zepbound results provide options for patients seeking to reduce dosage or move to a non-injectable format.

The Strategic Role of Foundayo

Foundayo represents a shift in the delivery mechanism of incretin therapy. While Zepbound is an injectable, Foundayo is a pill, addressing a primary point of patient friction. However, the clinical distinction is more than just the method of administration. Foundayo is a different molecule with a different mechanism than Zepbound, meaning the maintenance math for the two drugs differs.

The ability to transition patients from an injectable to an oral maintenance dose is a critical commercial and clinical objective. It allows for a tiered treatment lifecycle: an aggressive induction phase using high-dose injectables to reach target weight, followed by a maintenance phase using an oral pill to sustain those results. This transition reduces the burden of frequent injections while attempting to suppress the biological triggers that lead to weight regain.

Weight regain remains one of the biggest challenges in obesity care, and is often the result of treatment interruptions that cause biology to work against patients, undoing the progress they’ve made.

Louis J. Aronne, M.D., FACP, DABOM, founder and Chair Emeritus of the American Board of Obesity Medicine and Lilly consultant

Financial Implications and Market Valuation

These clinical results arrive as Eli Lilly continues to dominate the pharmaceutical sector’s valuation. In November 2025, the company became the first health-care company in the world to reach a $1 trillion market capitalization. The company’s financial trajectory reflects the massive demand for obesity and diabetes interventions.

According to 2025 data, Lilly reported revenue of US$65.18 billion, with operating income of US$26.30 billion and net income of US$20.64 billion. The company’s ability to expand its portfolio from a single high-dose injectable to a suite of maintenance options—including oral pills like Foundayo—broadens its total addressable market. By providing a viable “off-ramp” from MTD injectables to maintenance doses, Lilly can increase long-term patient adherence and extend the duration of the treatment cycle.

The competitive tension with Novo Nordisk’s Wegovy is evident in the ATTAIN-MAINTAIN trial, which specifically measured the transition from Wegovy MTD to Foundayo. The finding that patients switched from Wegovy to Foundayo maintained all but 0.9 kg of weight loss suggests that Foundayo may be a competitive maintenance option for patients currently using a competitor’s injectable therapy.

Clinical Outlook for Long-Term Care

The publication of these results in The Lancet and Nature Medicine provides the medical community with a framework for managing obesity as a chronic condition rather than a temporary weight-loss goal. The data suggests that while MTD is the most effective for absolute maintenance, lower doses and oral alternatives provide acceptable outcomes for a significant portion of the population.

The primary endpoint for these trials was to demonstrate that continuing Zepbound at a reduced 5 mg dose or at MTD was superior to a placebo in terms of percent weight maintenance. Both Zepbound MTD and Zepbound 5 mg met the primary and all key secondary endpoints in SURMOUNT-MAINTAIN after 60 weeks of initial treatment.

The focus now shifts to how clinicians will implement these transitions in real-world settings. The transition from an injectable to an oral molecule involves different pharmacokinetics, and the variation in weight regain (0.9 kg for Wegovy-to-Foundayo vs. 5.0 kg for Zepbound-to-Foundayo) indicates that the starting therapy may influence the success of the maintenance switch. As the market for incretin therapies matures, the ability to precisely calibrate maintenance doses will likely become the primary differentiator between pharmaceutical providers.