On 13 May, at the 33rd European Congress on Obesity in Istanbul, Türkiye, findings from the Phase 3b ATTAIN-MAINTAIN trial (NCT06584916) were presented, assessing Eli Lilly’s Foundayo (orforglipron) for the maintenance of body weight reduction in adults with obesity or overweight who had previously achieved substantial weight loss on Wegovy (semaglutide) or Zepbound (tirzepatide). The analysis aimed to evaluate whether patients could successfully transition from weekly injectable GLP-1-based therapy to a once-daily oral agent while sustaining their weight loss.
ATTAIN-MAINTAIN was a randomised, double-blind, placebo-controlled trial enrolling participants who had completed the SURMOUNT-5 study and achieved at least 5% weight loss. Two cohorts were included: Cohort 1 (TZP; N=205), comprising participants from the tirzepatide arm of SURMOUNT-5 (Maximum Tolerated Dose [MTD]: 10mg or 15mg), and Cohort 2 (SEMA; N=171), comprising participants from the semaglutide arm (MTD: 1.7mg or 2.4mg). Within each cohort, participants were randomised to orforglipron MTD or placebo for 52 weeks. Orforglipron was dose-escalated from a 9mg tablet at week 0 to 14.5mg at week 4 and then to the MTD of 17.2mg at week 8. Participants regaining ≥50% of their initial SURMOUNT-5 weight reduction from week 24 were offered rescue orforglipron. The primary endpoint was the proportion of weight loss maintained among participants who had reached a weight plateau during SURMOUNT-5.
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In results presented at ECO 2026 by Carel W. le Roux, MBChB, MSC, FRCP, FRCPath, PhD, Director of the Metabolic Medicine Group and Professor of Metabolic Medicine at Ulster University; and Louis J. Aronne, MD, FACP, Professor of Metabolic Research at Weill Cornell Medical College and Director of the Comprehensive Weight Control Center, orforglipron met the primary endpoint in both cohorts. In the TZP cohort, orforglipron maintained 78.0% of SURMOUNT-5 weight reduction versus 49.8% with placebo (ETD: 28.2 percentage points; p<0.001), while in the SEMA cohort, orforglipron maintained 82.4% versus 38.3% with placebo (ETD: 44.1 percentage points; p<0.001).
Participants switching from tirzepatide to orforglipron maintained ~20kg of weight lost during SURMOUNT-5, regaining ~5kg during ATTAIN-MAINTAIN, while those switching from semaglutide to orforglipron maintained ~18kg, with minimal (~1kg) regain. Rescue therapy requirements were substantially lower with orforglipron than with placebo (16.8% versus 48.8% in the TZP cohort; 21.9% versus 64.6% in the SEMA cohort), reinforcing its role in preventing weight regain. Cardiometabolic improvements achieved during SURMOUNT-5 were largely preserved, including sustained reductions in waist circumference (~18cm in TZP cohort and ~15cm in TZP cohort), lipid parameters, and systolic blood pressure. The safety profile was consistent with the GLP-1 class and prior orforglipron studies, with no hepatic safety signal and low rates of gastrointestinal adverse events. Transition to the initial 9mg dose was well tolerated, with no early dose reductions required.
Key opinion leaders interviewed by GlobalData suggest orforglipron could expand the obesity treatment market, driven by its oral formulation, lack of refrigeration requirements, and ease of administration—features likely to drive uptake in primary care, among needle-averse patients, and in long-term maintenance settings.
Overall, these findings position orforglipron as a clinically meaningful option for maintaining weight loss following injectable incretin therapy, offering an alternative to treatment discontinuation while preserving both weight and cardiometabolic benefits. According to GlobalData’s Pharma Intelligence Center, there are currently 48 Phase III, 112 Phase II, and 158 Phase I candidates for overweight and obesity in development globally, underscoring the considerable competitive landscape into which orforglipron now enters.
