Lilly says Foundayo and lower-dose Zepbound maintained weight loss in two trials
Two Lilly trials found people kept most of their weight loss after moving from high-dose injectables to oral Foundayo or lower-dose Zepbound.
Eli Lilly announced on May 12, 2026 that two late-phase trials found people maintained most or all of their weight loss after stepping down from higher doses of injectable incretin therapy to Foundayo (orforglipron) or to a lower 5 mg dose of Zepbound (tirzepatide) [1]. Detailed results were presented at the 33rd European Congress on Obesity and published in The Lancet and Nature Medicine [1].
SURMOUNT-MAINTAIN enrolled 441 adults with obesity or overweight with weight-related health problems, none with type 2 diabetes [1]. All first received open-label Zepbound at their maximum tolerated dose -- 10 mg or 15 mg -- for 60 weeks [1]. Those who lost at least 5% of body weight and tolerated the drug were then randomly assigned to keep taking Zepbound at the same dose, drop to 5 mg, or take a placebo for another 52 weeks [1]. At week 112, people who stayed at their maximum tolerated dose preserved all of their earlier weight loss, while those who stepped down to 5 mg maintained all but 5.6 kg on average [1]. In raw terms, the maximum-tolerated-dose group went from an average of 89.5 kg (197.3 lb) after the weight-loss phase to 88.7 kg (195.6 lb) after 52 weeks of maintenance; the 5 mg group went from 89.0 kg (196.2 lb) to 94.6 kg (208.6 lb) [1].
ATTAIN-MAINTAIN randomized 376 people in the United States who had finished the SURMOUNT-5 trial, which compared Zepbound and Wegovy head to head [1]. Participants had reached a weight plateau, and they were assigned in a 3:2 ratio to take once-daily oral Foundayo at maximum tolerated doses of 14.5 mg or 17.2 mg, or placebo, for 52 weeks [1]. People who switched from Wegovy (semaglutide) maintained all but 0.9 kg of their prior loss; those who switched from Zepbound maintained all but 5.0 kg -- 82.4% and 78.0% of earlier weight loss, respectively [1]. Average weight in the Wegovy group was 95.0 kg (209.4 lb) at the switch and 95.9 kg (211.4 lb) a year later, and in the Zepbound group 90.9 kg (200.4 lb) and 95.9 kg (211.4 lb) [1]. Starting at week 24, anyone who regained 50% or more of the weight lost in SURMOUNT-5 could receive "rescue" Foundayo up to the maximum tolerated dose [1].
Side effects were consistent with earlier Phase 3 studies, Lilly said [1]. In ATTAIN-MAINTAIN, with Foundayo versus placebo, nausea occurred in 18.8% versus 4.1%, constipation in 13.1% versus 4.1%, vomiting in 8.3% versus 3.4% and diarrhea in 7.4% versus 7.5% [1]. Discontinuation because of side effects ranged from 4.8% to 7.2% on Foundayo and 6.3% to 7.6% on placebo, depending on which drug participants had taken before [1]. During the maintenance phase of SURMOUNT-MAINTAIN, diarrhea, vomiting and nausea were the most common events; discontinuation because of side effects was 0% at the maximum tolerated dose, 0.7% at 5 mg and 0% on placebo [1].
"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," said Louis J. Aronne, an obesity specialist and Lilly consultant, in the announcement [1]. Kenneth Custer, president of Lilly Cardiometabolic Health, said patients "need more options they can stay on for the long run" [1].
Why it matters for patients
These drugs are usually studied as people move up in dose. These two trials looked at the opposite direction: what happens when someone moves down or over to a different product instead of stopping [1]. For people who cannot or do not want to stay on a maximum tolerated injectable dose, the results suggest that a lower Zepbound dose or once-daily oral Foundayo can hold most of the weight lost over the following year, at least among people who tolerated the higher dose [1].
Foundayo is a once-daily oral GLP-1 pill that the company says can be taken any time of day without restrictions on food or water intake, which is a different routine from a weekly injection [1]. Lilly notes that the ATTAIN-MAINTAIN trial used an investigational formulation of Foundayo at dosages equivalent to the approved tablets, so the exact product tested is not identical to what is sold [1]. The trial also allowed some participants to receive extra "rescue" medication, a design that can make maintenance results look better than they would without it [1].
What is not yet known
The announcement did not disclose how much weight participants on placebo regained in either trial, so the size of the step-down effect compared with no treatment is not visible in these numbers [1]. Whether the maintenance holds beyond one year has not been reported [1]. No information was included on cost, insurance coverage for step-down strategies, or whether these results will change the drugs' FDA labels [1].
Sources
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