Patients who lost weight on high-dose incretin-based injectables can maintain most of that loss long-term after switching to a lower dose of tirzepatide or to the oral GLP-1 receptor agonist orforglipron, according to two Phase 3b trials presented at the 33rd European Congress on Obesity and published in The Lancet and Nature Medicine.
Eli Lilly and Company announced the results on May 12 local time. The studies, SURMOUNT-MAINTAIN and ATTAIN-MAINTAIN, evaluated weight maintenance after an initial 60-week treatment period with the maximum tolerated dose of tirzepatide.
In SURMOUNT-MAINTAIN, patients who continued the maximum tolerated dose of tirzepatide for another year maintained all prior weight loss. Those who stepped down to tirzepatide 5 mg regained an average of 5.6 kg but still kept most of their original loss. At week 112, the maximum-dose group averaged 88.7 kg (down from a baseline of 112.2 kg), while the 5 mg group averaged 94.6 kg (down from 113.4 kg).
ATTAIN-MAINTAIN enrolled adults who had completed the SURMOUNT-5 study. Patients who switched from semaglutide to oral orforglipron regained an average of 0.9 kg after one year, while those switching from tirzepatide to orforglipron regained an average of 5.0 kg. The semaglutide-to-orforglipron group started SURMOUNT-5 at 113.5 kg, entered ATTAIN-MAINTAIN at 95.0 kg, and ended at 95.9 kg. The tirzepatide-to-orforglipron group started at 115.8 kg, entered at 90.9 kg, and ended at 95.9 kg.
Safety profiles in both trials were consistent with earlier Phase 3 studies. In SURMOUNT-MAINTAIN, common adverse events during maintenance included diarrhea (7.2% in the maximum-dose group, 4.9% in the 5 mg group, 1.1% placebo), vomiting (6.5%, 0.7%, 0%), and nausea (5.8%, 4.2%, 2.2%). Discontinuation rates due to adverse events were 0%, 0.7%, and 0%, respectively. In ATTAIN-MAINTAIN, orforglipron versus placebo showed 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%).
"Weight regain remains one of the biggest challenges in obesity treatment," said Dr. Louis Aronne, founder and emeritus chairman of the American Board of Obesity Medicine. "These SURMOUNT-MAINTAIN and ATTAIN-MAINTAIN results show that lower-dose tirzepatide and orforglipron can contribute to long-term weight maintenance."
Kenneth Custer, president of Lilly's cardiovascular and metabolic disease division, added: "Obesity is a chronic disease requiring long-term treatment, and patients need more options to continue therapy over time. It is encouraging that both tirzepatide and the once-daily oral GLP-1 receptor agonist orforglipron demonstrated sustained weight-loss maintenance."
Orforglipron is not yet approved by South Korea's Ministry of Food and Drug Safety; its approval status and timeline will depend on regulatory review.
Source: Read the original report | Published: May 20, 2026