- New post-hoc analyzes suggest that females taking the oral weight loss drug or forglipron experienced substantial weight loss regardless of whether they were premenopausal, perimenopausal, or postmenopausal.
- The highest dose orforglipron produced weight reductions of up to 14.4% in women without type 2 diabetes and up to 13.6% in women with type 2 diabetes.
- Additionally, an indirect comparison found that orforglipron was associated with greater weight loss than oral semaglutide.
- The indirect comparison also suggests that forglipron was associated with greater reductions in blood sugar, but the findings should be interpreted with caution.
Orforglipron, marketed as Foundayo and produced by Eli Lilly, is a once-daily oral GLP-1 receptor agonist, with Food and Drug Administration (FDA) approval for adults with obesity, or overweight with weight-related medical problems. Notably, unlike other oral GLP-1s, it does not require the fasting and water restrictions associated with oral semaglutide.
New analyzes from previous trials, presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD) in Milan, Italy, suggest that orforglipron’s effects on body weight may be consistent across different stages of menopause.
Separate analyzes also indicate that the drug may produce greater weight loss and reductions in blood glucose than oral semaglutide in adults with type 2 diabetes, although the comparison was indirect.
The findings come as researchers continue to investigate whether oral GLP-1 treatments can provide an alternative to injectable medications for people living with obesity and type 2 diabetes. However, it is important to note that these reports are based on conference presentations, so the analyzes have yet to be published in a peer-reviewed journal.
Weight loss seen across menopause stages with Foundayo
One of the new analyzes examined females participating in the phase 3 ATTAIN 1 and ATTAIN 2 trials.
The ATTAIN-1 trial evaluated orforglipron in adult participants with obesity or overweight with weight-related comorbidities, whereas ATTAIN-2 looked at people living with both overweight or obesity and diabetes.
The researchers analyzed women by menopause status, including premenopausal, perimenopausal, and postmenopausal. Notably, women receiving orforglipron experienced significant reductions in body weight across all 3 menopausal groups
In ATTAIN-1, a 36 milligram (mg) dose of orforglipron was associated with weight reductions of roughly 12.8% in premenopausal females, 14.4% in perimenopausal females, and 14.1% in postmenopausal females.
In ATTAIN-2, the corresponding reductions were approximately 11.3%, 8.9%, and 13.6%, respectively.
The analysis also found reductions in waist circumference. Across the studies, waist circumference decreased by as much as 12.5 centimeters (cm) in participants receiving orforglipron. Up to 83% of women receiving the medication achieved at least 5% weight loss, compared with 30% of those receiving a placebo.
The researchers described the weight-loss effects as similar across menopause stages. However, the analysis was post hoc, meaning the researchers examined existing clinical trial data rather than designing trials specifically to test whether menopausal status altered the medication’s effectiveness.
“The findings show that orforglipron helps with weight loss regardless of menopausal stage,” Mir Ali, MD, bariatric surgeon, bariatric medicine specialist, and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the trials, told Medical News Today.
“Because post-menopausal women typically struggle with weight loss more than premenopausal women, this study highlights that the medication is beneficial across different menopausal stages.”
Ali noted the significance of the 14% weight loss but reminded that long-term results still need further investigation.
“Research indicates that a larger waist circumference, which reflects higher intra-abdominal fat, correlates with an increased risk for conditions such as diabetes and cardiovascular disease. Consequently, reducing waist circumference can help lower these health risks,” he added, highlighting how weight loss can improve clinical outcomes in many conditions.
How does orforglipron compare with oral semaglutide?
A separate analysis presented at the EASD meeting compared orforglipron with oral semaglutide in adults with type 2 diabetes.
Rather than being a direct head-to-head clinical trial, the analysis used data from two separate studies:
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 of oral semaglutide. Orforglipron was also associated with a 0.3 percentage-point greater reduction in HbA1c, a measure of average blood glucose levels.
Eli Lilly reported that alternative statistical approaches produced estimates ranging from 1.5% to 2.4% greater weight loss and from 0.3% to 0.6% greater HbA1c reduction with orforglipron.
However, these findings should not be interpreted as evidence from a direct comparison between the two medications. Indirect treatment comparisons can be affected by differences between the underlying studies and their participants.
In the head-to-head ACHIEVE-3 trial, orforglipron was compared with lower doses of oral semaglutide. At 52 weeks, the 17.2-mg orforglipron group lost an average of 9.2% of body weight, compared with 5.3% with 14 mg of oral semaglutide. HbA1c reductions were 2.2% and 1.4%, respectively.
Both orforglipron and semaglutide are GLP-1 receptor agonists. If one proves more effective than the other, differences in absorption or bioavailability may be contributing factors. Further research and longer-term studies are needed to determine the reasons behind any differences in efficacy.
What do the findings mean for obesity or menopause?
Together, the analyzes add to evidence that oral orforglipron can promote clinically meaningful weight loss in people with obesity or overweight, including females at different stages of menopause.
The menopause findings may be particularly relevant because hormonal changes during the menopause transition can be accompanied by changes in body composition and weight distribution.
However, the new analysis does not establish that menopause status has no effect on treatment response. Rather, it found broadly similar weight reductions among the groups studied.
The semaglutide analysis provides another point of comparison, but its indirect design is an important limitation. Direct randomized trials comparing the same doses and populations would provide stronger evidence about differences between the medications.
It is also important to distinguish the populations involved. The semaglutide comparison examined adults with type 2 diabetes, whereas the ATTAIN studies included people with overweight or obesity, with ATTAIN-2 specifically enrolling people who also had type 2 diabetes. Results from one population should therefore not automatically be applied to another.
