ATTAIN-MAINTAIN: Switching From GLP-1 Injections to Orforglipron
ATTAIN-MAINTAIN is Lilly's phase 3b trial that tested switching people who had plateaued on Wegovy or Zepbound injections to an orforglipron (Foundayo) pill. People switching from semaglutide kept almost all of their weight loss over 52 weeks. People switching from tirzepatide kept most of it, but regained about 5 kg on average. Both groups did far better than those switched to placebo, though the trial never compared the pill with simply staying on the injection.
Key takeaways
- 376 adults who had finished 72 weeks of Zepbound or Wegovy in SURMOUNT-5 were randomized to orforglipron or placebo for 52 weeks.
- Among people who had plateaued, the semaglutide-to-orforglipron group maintained 79.3% of their weight loss, compared with 37.6% on placebo.
- The tirzepatide-to-orforglipron group maintained 74.7%, compared with 49.2% on placebo, and regained about 5 kg on average under the efficacy estimand.
- No arm stayed on the injection, so the trial cannot show whether switching is as good as continuing.
- The trial used development dose numbers (12, 24, 36 mg) that differ from Foundayo's marketed tablet strengths.
Where the data come from
Lilly announced topline results on December 18, 2025. The full paper, Aronne and colleagues' "Orforglipron for maintenance of body weight reduction," appeared in Nature Medicine online on May 13, 2026 (volume 32, pages 2679 to 2687). It was presented the same week as a late-breaking abstract at the European Congress on Obesity in Istanbul, Healio reported. The registration number is NCT06584916, and Eli Lilly funded the study.
This article reads the press release and the published paper side by side. The headline numbers differ between them, and the differences explain what the trial does and does not show.
How the trial was built
Every participant came from SURMOUNT-5, the 72-week head-to-head trial of Zepbound (tirzepatide 10 or 15 mg) against Wegovy (semaglutide 1.7 or 2.4 mg). In that trial, mean weight loss was 20.2% on tirzepatide and 13.7% on semaglutide, per Lilly.
The key design choices, from Lilly's release and the trial summaries:
- Who qualified: SURMOUNT-5 completers with obesity, or overweight plus a weight-related condition. The primary analysis covered people at a weight plateau, defined as less than 5% body weight change between weeks 60 and 72.
- Randomization: 3:2 to orforglipron or placebo, double-blind. The tirzepatide cohort had 205 people (125 orforglipron, 80 placebo) and the semaglutide cohort had 171 (105 orforglipron, 66 placebo), per GPnotebook's summary of the paper.
- Dosing: Orforglipron started at 12 mg and increased every 4 weeks to the maximum tolerated dose of 24 or 36 mg.
- Rescue: Anyone who regained 50% or more of their SURMOUNT-5 loss could get rescue orforglipron, and placebo patients who met that threshold were started on rescue at 24 weeks, per Healio.
- Primary endpoint: Percent of SURMOUNT-5 weight reduction maintained at week 52.
Two features matter for patients. First, nobody in the trial continued their injection, so there is no "stay on Wegovy or Zepbound" comparison arm. Second, the placebo group was not a pure "stop everything" group after week 24, because rescue therapy was allowed.
The headline results, two ways
The published paper's primary analysis uses a treatment-regimen estimand. It counts everyone as randomized, including people who stopped the pill or needed rescue. Lilly's December press release led with the efficacy estimand, which estimates what happens if people stay on the assigned treatment.
| Result at week 52 (plateau group) | Semaglutide → orforglipron | Semaglutide → placebo | Tirzepatide → orforglipron | Tirzepatide → placebo |
|---|---|---|---|---|
| Weight loss maintained (treatment-regimen estimand, primary) | 79.3% | 37.6% | 74.7% | 49.2% |
| Treatment difference (95% CI) | 41.7 points (24.4 to 59.0) | 25.5 points (14.5 to 36.5) | ||
| Kept at least 80% of their loss | 55% | 6.9% | 43.7% | 16.4% |
| Weight at switch → week 52 (efficacy estimand) | 95.0 → 95.9 kg | n/a | 90.9 → 95.9 kg | n/a |
Sources: Aronne et al., Nature Medicine 2026 (abstract); "kept at least 80%" figures from Healio; Lilly press release, Dec. 18, 2025.
Lilly's table also lists the starting weights before SURMOUNT-5: 113.5 kg for the semaglutide group and 115.8 kg for the tirzepatide group. Working from those figures, the semaglutide group lost about 18.5 kg on the injection and regained about 0.9 kg on the pill. The tirzepatide group lost about 24.9 kg and regained about 5.0 kg. That is our arithmetic from Lilly's published means, and it reflects the more favorable efficacy estimand.
The 24-week snapshot
Because placebo patients could get rescue after week 24, Lilly also reported a post hoc 24-week comparison, the last clean look at pill versus placebo. From the switch, the semaglutide-to-orforglipron group changed by −0.1 kg versus +9.4 kg on placebo. The tirzepatide-to-orforglipron group changed by +2.6 kg versus +9.1 kg on placebo, per the release. Post hoc means the analysis was not prespecified, so it supports the main result but doesn't stand alone.
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Why the tirzepatide group regained more
The trial doesn't answer this directly, but the design points to two likely factors. Tirzepatide acts on two receptors (GIP and GLP-1), and orforglipron acts only on GLP-1. Tirzepatide patients had also lost more weight, so they had more to hold onto. An independent commentator quoted by Healio raised the receptor mismatch as a hypothesis, not a finding.
Lead author Louis Aronne put the absolute numbers plainly at the press conference: about 20 kg maintained after switching from tirzepatide, and about 18 kg maintained with roughly 1 kg regained after switching from semaglutide.
Safety and tolerability
Side effects were mostly gastrointestinal (nausea, constipation, vomiting, diarrhea) and mostly mild to moderate. No liver safety signal was seen. Discontinuation because of adverse events was:
| Group | Stopped due to adverse events |
|---|---|
| Semaglutide → orforglipron | 4.8% |
| Semaglutide → placebo | 7.6% |
| Tirzepatide → orforglipron | 7.2% |
| Tirzepatide → placebo | 6.3% |
Source: Lilly press release, Dec. 18, 2025; also reported by HCPLive.
Healio reported 4 severe adverse events with orforglipron versus 1 with placebo. The low dropout rates are notable because these participants had already tolerated a GLP-1 injection for over a year. People starting a GLP-1 for the first time may have a different experience.
What the trial cannot tell you
- Whether switching is as good as staying put. There was no arm that continued Wegovy or Zepbound. The comparison is pill versus stopping.
- What happens after one year. The commentator in Healio noted that the graphs suggest regain may begin late in follow-up.
- What happens to muscle. No DXA body-composition data were reported.
- Whether it applies to you. The commentator in Healio described the cohort as mostly young, white, and female with relatively low disease burden, and everyone was selected for having completed SURMOUNT-5 and reached a plateau.
- Whether the drug was independently evaluated. Lilly funded the trial, and several authors have financial ties to the company, per Epocrates.
How the trial maps to the Foundayo label
The FDA approved Foundayo on April 1, 2026, with tablets labeled 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg. The prescribing information lays out one escalation path: start at 0.8 mg and step up after at least 30 days at each dose. The label reports its pooled trial data under these marketed strengths, while ATTAIN-MAINTAIN used the development numbers (12 mg start, 24 or 36 mg maintenance) and moved faster, every 4 weeks starting at 12 mg.
The label's dosing section does not set out a separate schedule for people coming off an injection. How fast to titrate after a switch, and whether to overlap or leave a gap, is a prescriber decision. Patients who have been off any GLP-1 for a while should expect to start low again.
Cost context for a switch
Price is one reason people ask about switching. As of October 2026, LillyDirect lists Foundayo at $149 to $299 a month self-pay depending on dose. Reuters reported in April 2026 that Zepbound's self-pay program runs $299 to $449 a month and that Wegovy injection cash pricing was $349 a month. Prices change often, so check the manufacturer pages before deciding.
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Frequently asked questions
Did people keep their weight off after switching from Wegovy to orforglipron?
Mostly. Among people who had plateaued, the semaglutide-to-orforglipron group maintained 79.3% of their weight loss at 52 weeks under the primary analysis, versus 37.6% on placebo. Under Lilly's efficacy estimand, average regain was about 0.9 kg.
What about switching from Zepbound?
The tirzepatide-to-orforglipron group maintained 74.7% of their loss versus 49.2% on placebo. Under the efficacy estimand they regained about 5 kg on average, from 90.9 kg to 95.9 kg.
Is switching to the pill as good as staying on the injection?
The trial cannot say. No group continued Wegovy or Zepbound, so orforglipron was compared only with placebo.
Were the trial doses the same as Foundayo tablets?
The trial used development dose numbers, starting at 12 mg and maintaining at 24 or 36 mg. Foundayo tablets are labeled 0.8 to 17.2 mg, so ask your prescriber how they correspond.
Sources
- Aronne LJ et al. Orforglipron for maintenance of body weight reduction: ATTAIN-MAINTAIN. Nature Medicine 2026 (record and abstract)
- Eli Lilly press release: orforglipron helped people maintain weight loss after switching (Dec. 18, 2025)
- Healio: Adults switching from injectable drug to Foundayo maintain majority of weight loss
- GPnotebook: ATTAIN-MAINTAIN trial summary
- HCPLive: Orforglipron maintains weight loss in patients switching from semaglutide or tirzepatide
- Epocrates: GLP-1 weight loss can be maintained
- Foundayo US Prescribing Information
- LillyDirect: Foundayo pricing
- Reuters factbox: Pricing and availability of Novo, Lilly weight-loss drugs (April 2026)
Medical disclaimer: This article is general information, not medical advice, and does not replace a licensed clinician who knows your history. Approvals, labels, coverage and prices change; check the linked sources and talk with your prescriber or pharmacist before making decisions about any medication.