ATTAIN-MAINTAIN trial - orforglipron for maintenance of body weight reduction

Orforglipron is a once-daily, nonpeptide GLP-1 receptor agonist (RA).

The ATTAIN-MAINTAIN study was to assess the efficacy and safety of orforglipron compared with placebo, in maintenance of body weight reduction after 72 weeks of tirzepatide (cohort 1) or semaglutide (cohort 2) treatment in participants with obesity or body mass index (BMI) ≥27 kg/m² with obesity-related complications who had previously participated in the SURMOUNT-5 study (1):

• trial examined the maintenance of body weight reduction with treatment of orforglipron among participants who previously completed SURMOUNT-5 and received 72 weeks of either tirzepatide (cohort 1) or semaglutide (cohort 2)
• study included a screening period of up to 2 weeks after completion of SURMOUNT-5, a 52-week treatment period and a 2-week safety follow-up
• total of 205 participants in cohort 1 were randomized to treatment (N = 125 orforglipron 36 mg or maximum tolerated dose (MTD), N = 80 placebo) and 171 participants in cohort 2 were randomized to treatment (N = 105 orforglipron 36 mg or MTD, N = 66 placebo)
  • Cohort 1 participants who achieved body weight plateau maintained a model-based estimate (MBE) of 74.7% of body weight reduction with orforglipron compared with an MBE of 49.2% with placebo, resulting in an estimated treatment difference of MBE 25.5% (95% confidence interval 14.5 to 36.5); P < 0.001; treatment-regimen estimand) at week 52
  • Cohort 2 participants who achieved body weight plateau maintained an MBE of 79.3% of body weight reduction with orforglipron compared with an MBE of 37.6% with placebo, resulting in an estimated treatment difference of MBE 41.7% (95% confidence interval 24.4 to 59.0); P < 0.001; treatment-regimen estimand) at week 52
• most common adverse events were gastrointestinal effects, which were mostly mild to moderate in severity

Study authors concluded:

“..These data demonstrate orforglipron’s potential as a globally scalable option for minimizing weight changes after injectable therapy…”

Reference:

1. Aronne LJ et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Medicine (2026).