Once-daily treatment with the highest orforglipron dose is associated with significant reductions in body weight and waist circumference at week 72 in women with obesity or overweight, regardless of menopausal status, according to a post hoc analysis of the phase III ATTAIN-1 and -2 trials presented at ADA 2026.
This post hoc analysis included 2,003 (ATTAIN-1) and 754 (ATTAIN-2) women who were obese or overweight (BMI ≥27 kg/m2) and stratified according to menopausal status (pre-, peri-, and postmenopausal). Participants were randomized to receive once-daily oral orforglipron 6, 12, or 36 mg (n=2,178 [ATTAIN-1] and n=983 [ATTAIN-2]) or placebo (n=949 and n=630, respectively) in addition to a healthy diet and physical activity. [ADA 2026, abstract 1716-P]
The present study focused on the highest dose of orforglipron, 36 mg, which corresponds to an equivalent tablet dose of 17.2 mg that has already been approved in the US. [Diabetes Obes Metab 2026;28:5803–5809]
During the ATTAIN‑1 trial, women treated with orforglipron had significantly greater reductions in body weight at week 72 compared with placebo, irrespective of menopausal status (-12.81 percent vs -0.25 percent [premenopausal], -14.38 percent vs -1.02 percent [perimenopausal], and -14.07 percent vs -0.62 percent [postmenopausal]).
Similarly, in the ATTAIN-2 trial, women with T2D, those who received orforglipron lost significantly more weight by week 72 than those on placebo, across all menopausal cohorts (-11.30 percent vs -2.88 percent [premenopausal], -8.88 percent vs -1.57 percent [perimenopausal], and -13.62 percent vs -2 percent [post-menopausal]).
In both ATTAIN‑1 and ‑2 trials, participants receiving orforglipron also experienced a significant reduction in waist circumference of up to 12.51 percent and 11.04 percent, respectively, across all menopausal stages, compared with placebo (2.35 percent and 2.51 percent, respectively).
Significantly more patients receiving orforglipron also achieved a weight loss threshold of ≥20 percent by week 72, across all menopausal stages, compared with those receiving placebo. In the ATTAIN-1 trial, the rates were 24.18 percent vs 1.63 percent for premenopausal, 29.94 percent vs 0.72 percent for perimenopausal, and 23.79 percent vs 0.55 percent for postmenopausal women. In ATTAIN-2, the corresponding rates were 32.09 percent vs 0 percent, 9.74 percent vs 0 percent, and 21.69 percent vs 0 percent.
Additionally, more orforglipron- vs placebo-treated women moved to a lower waist-to-height ratio category at week 72 across all menopausal cohorts in both trials.
“Overall, orforglipron supports weight reduction in females across the spectrum of menopausal stages, demonstrated in both ATTAIN-1 and ATTAIN-2,” said the researchers.
“These findings underscore orforglipron’s efficacy in managing obesity at different menopausal stages,” they noted.