Lilly reports that Foundayo and lower-dose Zepbound maintain weight loss after stepping down

Eli Lilly on May 12, 2026 released detailed results from two late-phase trials testing whether people who lose weight on a high dose of injectable incretin therapy can hold onto it after stepping down — either to the once-daily oral pill Foundayo (orforglipron) or to a lower 5 mg dose of Zepbound (tirzepatide) ^[1]. The results were presented at the 33rd European Congress on Obesity and published in The Lancet (SURMOUNT-MAINTAIN) and Nature Medicine (ATTAIN-MAINTAIN) ^[1].

In both trials, the step-down groups kept most, but not all, of their earlier loss. Staying on the maximum tolerated injectable dose preserved the most weight ^[1].

What SURMOUNT-MAINTAIN found

SURMOUNT-MAINTAIN (NCT06047548) enrolled 441 adults with obesity or overweight with weight-related conditions and without type 2 diabetes ^[1]. Everyone took open-label Zepbound at their maximum tolerated dose (MTD) — 10 mg or 15 mg — for 60 weeks. Those who lost at least 5% and tolerated the drug were then randomized 3:3:2 to Zepbound 5 mg, Zepbound MTD, or placebo for a 52-week maintenance period ^[1].

At week 112, people who stayed on MTD preserved all of their prior weight loss on average, while those cut to 5 mg maintained all but 5.6 kg ^[1]. In raw numbers, the MTD group went from an average 112.2 kg (247.4 lbs) to 89.5 kg (197.3 lbs) after 60 weeks, then 88.7 kg (195.6 lbs) at the end of maintenance. The 5 mg group went from 113.4 kg (250.0 lbs) to 89.0 kg (196.2 lbs), then back up to 94.6 kg (208.6 lbs) ^[1]. Measured from the original baseline, total loss was 25.2 kg (22.4%) for MTD and 19.2 kg (17.0%) for the 5 mg group ^[1]. Both doses beat placebo on the primary endpoint and all key secondary endpoints, though Lilly's release does not give the placebo numbers ^[1].

What ATTAIN-MAINTAIN found

ATTAIN-MAINTAIN (NCT06584916) randomized 376 US participants who had finished the SURMOUNT-5 head-to-head trial and had hit a weight plateau, defined as less than 5% body weight change between weeks 60 and 72 ^[1]. They were assigned 3:2 to once-daily oral Foundayo at 14.5 mg or 17.2 mg, or placebo, for 52 weeks. Participants started at 9 mg and escalated every four weeks ^[1].

People who switched from Wegovy (semaglutide) MTD — 1.7 mg or 2.4 mg — to Foundayo maintained all but 0.9 kg of their earlier loss. Those who switched from Zepbound MTD to Foundayo maintained all but 5.0 kg ^[1]. Put another way, the two groups maintained 82.4% and 78.0% of their previously achieved weight loss after a year ^[1]. Both groups ended at the same average weight, 95.9 kg (211.4 lbs), but they started the switch at different points: 95.0 kg for the Wegovy group and 90.9 kg for the Zepbound group ^[1].

One design note: starting at week 24, anyone who regained 50% or more of their SURMOUNT-5 weight loss was given rescue Foundayo ^[1]. The trial also used an investigational formulation of Foundayo at dosages Lilly describes as equivalent to the marketed tablets ^[1].

Side effects matched earlier Phase 3 data. With Foundayo versus placebo, the most common were nausea (18.8% vs. 4.1%), constipation (13.1% vs. 4.1%), vomiting (8.3% vs. 3.4%) and diarrhea (7.4% vs. 7.5%) ^[1]. In the Zepbound maintenance period, diarrhea, vomiting and nausea were most common, and discontinuation for adverse events was 0% on MTD, 0.7% on 5 mg and 0% on placebo ^[1].

Why it matters for patients

Many people on GLP-1 and dual-incretin drugs ask whether they can eventually take less, or switch to a pill, without watching the weight come back. These are the first large, randomized answers Lilly has published on that question ^[1].

The trade-off is visible in the numbers. Staying at the top injectable dose preserved the most weight; stepping down to 5 mg Zepbound or to an oral drug preserved most of it, with average regain of roughly 5 to 5.6 kg in the Zepbound-to-step-down groups and under 1 kg for the Wegovy-to-Foundayo group ^[1]. Averages also hide individual variation — some participants regained enough to need rescue treatment ^[1].

What happens next

Foundayo is already FDA-approved for chronic weight management in adults with obesity or overweight with weight-related conditions ^[1]. Lilly says orforglipron is also being studied in type 2 diabetes, obstructive sleep apnea, knee osteoarthritis pain, hypertension, peripheral artery disease and stress urinary incontinence, and tirzepatide trials in chronic kidney disease and obesity-related morbidity/mortality are ongoing ^[1]. The release does not say whether Lilly will seek any labeling change based on these maintenance results, or when ^[1].