orforglipron · 72 weeks
ATTAIN-1
Orforglipron, an oral small-molecule GLP-1 receptor agonist, reduced weight at 72 weeks by 11.2% with 36 mg, 8.4% with 12 mg and 7.5% with 6 mg, compared with 2.1% on placebo.
Randomized controlled trial
ATTAIN-MAINTAIN: the orforglipron pill after weight-loss shots
On orforglipron, 74.7% of the weight lost on tirzepatide was maintained, versus 49.2% on placebo (difference of 25.5 points; 95% CI, 14.5 to 36.5); after semaglutide, 79.3% versus 37.6% (difference of 41.7 points; 95% CI, 24.4 to 59.0).
Aronne LJ et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nature Medicine, 2026. DOI: 10.1038/s41591-026-04386-7
- Prepared by
- Alex Gonzalez
- Last updated
- Sources
- 4 sources
No clinical review. No advertising from drug companies and no affiliate links.How we work
Key facts
- Drug
- orforglipron
- Design
- Randomized controlled trial
- Participants
- 376
- Duration
- 52 weeks
- Funding
- Eli Lilly
- Registry
- NCT06584916
- Population
- 376 adults without diabetes who had completed the 72 weeks of the SURMOUNT-5 trial on tirzepatide (205, cohort 1) or semaglutide (171, cohort 2) and lost at least 5% of their weight, at 29 sites in the United States, randomized (3:2) to orforglipron or placebo. Mean weight on entry was 90.1 kg in the tirzepatide cohort and 94.4 kg in the semaglutide cohort.
- Primary outcome
- Share of the weight loss achieved in SURMOUNT-5 that was maintained at 52 weeks with daily oral orforglipron (36 mg or the maximum tolerated dose of 24 or 36 mg as investigational capsules, equivalent to 14.5 and 17.2 mg tablets) versus placebo, in participants who had reached a weight plateau (less than 5% change between weeks 60 and 72 of SURMOUNT-5). Each cohort was analyzed separately.
What it found
On orforglipron, 74.7% of the weight lost on tirzepatide was maintained, versus 49.2% on placebo (difference of 25.5 points; 95% CI, 14.5 to 36.5); after semaglutide, 79.3% versus 37.6% (difference of 41.7 points; 95% CI, 24.4 to 59.0). These figures refer to participants who had reached the weight plateau, and all key secondary objectives were met. The most common adverse effects were digestive, mostly mild or moderate, and between 4.8% and 7.3% stopped orforglipron because of adverse effects, versus 2.5% and 3.0% on placebo.
Limitations
Funded by Eli Lilly, which makes orforglipron and tirzepatide. There was no group that stayed on the injectable, so it does not compare orforglipron with continuing tirzepatide or semaglutide. It lasted one year, only in the United States and with people without diabetes who came from another trial. Doses are given as investigational capsules; the product approved in the United States uses tablets with different dose labels.
What it means for you
ATTAIN-MAINTAIN tested the orforglipron pill for keeping off weight lost on tirzepatide or semaglutide shots: over one year, it preserved 74.7% of the loss after tirzepatide and 79.3% after semaglutide, versus 49.2% and 37.6% on placebo. There was no group that stayed on the injectable, so it does not tell you whether switching to the pill works as well as continuing the shot. Any change of drug or dose is for your doctor to decide.
Further reading
Sources
The original paper and the records consulted for this summary, with the date they were accessed.
- Nature Medicine.Aronne LJ, et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med. 2026;32(7):2679-2687.accessed .
- National Library of Medicine (PubMed).PubMed record PMID 42120723 (abstract).accessed .
- National Library of Medicine (PubMed Central).PubMed Central full text PMC13375559 (sites, doses, baseline weight and discontinuations).accessed .
- ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT06584916 (registration and enrolment).accessed .