New post-hoc analyses of the phase 3 ATTAIN program indicate that the oral GLP-1 receptor agonist orforglipron (marketed as Foundayo) produced substantial weight reductions in females regardless of menopausal stage. The investigators divided women enrolled in ATTAIN-1 and ATTAIN-2 into premenopausal, perimenopausal, and postmenopausal groups and compared relative weight change. The article reported that the analyses were presented at the EASD annual meeting and have not yet appeared in a peer-reviewed journal.
In ATTAIN-1, a 36 mg dose was associated with weight reductions of roughly 12.8% in premenopausal women, 14.4% in perimenopausal women, and 14.1% in postmenopausal women. The ATTAIN-2 trial—enrolling people with overweight or obesity and type 2 diabetes—showed corresponding reductions of about 11.3%, 8.9%, and 13.6% across those menopausal strata. The source did not report the subgroup sample sizes or the specific statistical testing used for interaction by menopausal status.
Waist circumference also declined in the pooled analyses. Investigators reported decreases of up to 12.5 cm with orforglipron, and as many as 83% of women receiving the medication achieved at least 5% weight loss versus 30% on placebo. The study team observed that changes in central adiposity carry implications for cardiometabolic risk. A bariatric surgeon quoted in the source, who was not involved with the trials, said the results show benefit across menopausal stages but cautioned that long-term durability remains unproven.
These results were derived from post-hoc subgroup analyses—meaning the trials were not prospectively designed to test menopausal status as a primary modifier of effect. The investigators reported broadly similar weight reductions across groups, but the presentation did not provide sufficient detail in the source article to confirm whether menopausal status statistically modified treatment effect or whether there were differential safety signals by subgroup.
A separate analysis presented at the same meeting compared weight and glycemic outcomes for orforglipron versus oral semaglutide using indirect methods. The comparison drew on ACHIEVE-3, which evaluated orforglipron, and PIONEER PLUS, which examined higher doses of oral semaglutide. Because the approach pooled results from separate trials rather than randomizing participants between the two drugs, investigators and the article urged caution in interpretation.
Using the indirect comparison, the analysis found that people receiving 17.2 mg of orforglipron had, on average, 1.5 percentage points greater weight loss than those receiving 25 mg oral semaglutide. Orforglipron was also associated with a roughly 0.3 percentage-point greater reduction in HbA1c. The drug maker reported that alternative statistical approaches produced ranges: 1.5–2.4% greater weight loss and 0.3–0.6% greater HbA1c reduction favoring orforglipron.
The source also summarized a direct head-to-head element from ACHIEVE-3 that compared orforglipron with lower-dose oral semaglutide. At 52 weeks, the 17.2-mg orforglipron group lost an average of 9.2% of body weight versus 5.3% for 14 mg oral semaglutide; HbA1c reductions reported were 2.2% and 1.4% respectively. The presentation did not include a detailed adverse-event table in the source article, nor did it supply comparative tolerability metrics beyond those efficacy figures.
Both agents are GLP-1 receptor agonists. The investigators suggested that differences in absorption or bioavailability could contribute to between-drug efficacy differences, but the source did not report mechanistic data or pharmacokinetic details to substantiate those hypotheses.
The ATTAIN program enrolled adults with overweight or obesity, with ATTAIN-2 specifically including participants with type 2 diabetes; the semaglutide comparison focused on adults with type 2 diabetes. The source emphasized that populations differ between analyses and cautioned against applying results from one cohort directly to another. That distinction matters for both efficacy and safety interpretation.
Clinical endpoints reported in the conference material centered on percent weight change, proportions achieving predefined weight-loss thresholds, waist circumference, and HbA1c. The source did not provide additional cardiovascular or long-term metabolic outcome data. It also did not report subgroup-specific safety outcomes, rates of discontinuation, or adverse-event severity breakdowns for the menopausal or diabetes subsets within the summarized presentations.
Investigators and independent clinicians cited in the report noted the potential clinical relevance of 10–14% weight loss and reductions in waist circumference because those changes can affect cardiometabolic risk factors. However, the source also relayed expert caution that sustained benefit, long-term safety, and impacts on hard outcomes such as cardiovascular events remain to be evaluated.
All findings described in the source were presented at a scientific conference and have not been published in peer-reviewed journals; the article explicitly states this limitation. Several analyses were post hoc or indirect comparisons rather than prospective, randomized head-to-head trials, which raises risk of bias and confounding from between-study differences.
The source did not report sample sizes for menopausal subgroups, did not include detailed safety or adverse-event breakdowns for those subgroups, and did not provide long-term follow-up beyond the trial windows presented. Investigators called for direct randomized comparisons across equivalent doses and populations and for longer-term studies to define durability of weight loss, comparative safety, and effects on cardiometabolic endpoints.
The immediate unanswered questions—documented in the source—are whether menopausal status truly modifies treatment response when tested prospectively, whether the indirect advantages seen versus oral semaglutide hold in randomized head-to-head trials, and how long benefits and safety are maintained. These points will determine the strength of evidence clinicians can rely on for treatment selection.