Orforglipron Shows Strong Weight Maintenance in Phase 3 ATTAIN-MAINTAIN Trial

In the 52-week, randomized, double-blind, placebo-controlled, phase 3 ATTAIN-MAINTAIN trial (NCT06584916), orforglipron (Eli Lilly and Company) met all primary and key secondary end points for weight management compared to placebo, following weight loss on semaglutide (Wegovy; Novo Nordisk) or tirzepatide (Zepbound; Eli Lilly and Company). The findings revealed that patients who switched to orforglipron from semaglutide maintained all but 0.9 kg of their previously achieved weight loss on average.^1,2

“If approved for the treatment of obesity, orforglipron could provide a convenient alternative for the millions of individuals living with obesity around the globe to continue their long-term health journey,” Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, said in a news release.¹

How Does Orforglipron Aid Weight Management and Diabetes?

Orforglipron is an investigational, once-daily, oral glucagon-like peptide receptor agonist (GLP-1) that can be taken anytime without food or water restrictions. Orforglipron works by stimulating insulin release from the pancreas and slowing gastric emptying, which promotes satiety, reduces food intake, and leads to weight loss. The GLP-1 could aid weight management and promote a healthier lifestyle for individuals with obesity, identified as having a body mass index (BMI) of 30 or higher.¹

"Obesity is a chronic, progressive disease, and sustaining weight loss remains a significant challenge for many," Custer said.¹

What did ATTAIN-MAINTAIN Find?

The phase 3 study evaluated the efficacy and safety of once-daily orforglipron for maintaining weight loss in adults with obesity or overweight and weight-related comorbidities who had previously completed the SURMOUNT-5 (NCT05822830) trial. Patients included in the 72-week, multi-center, randomized, open-label, phase 3b SURMOUNT-5 trial were randomly assigned to receive semaglutide or tirzepatide, which aimed to assess the percentage of change from baseline body weight between both treatments.^1,3

A total of 376 individuals were included in the ATTAIN-MAINTAIN trial and were randomly assigned 3:2 to receive either orforglipron or placebo, alongside a healthy diet and physical activity. Patients started at 12 mg of orforglipron once daily, with doses increased every 4 weeks to the maximum tolerated dose of 24 mg or 36 mg¹

The primary endpoint of ATTAIN-MAINTAIN was to demonstrate orforglipron’s superiority to placebo in maintaining weight loss in participants who plateaued on tirzepatide or semaglutide in SURMOUNT-5.¹

Results from one year of treatment demonstrated that orforglipron met the primary endpoint and all key secondary endpoints, achieving superior weight management alongside a healthy diet and physical activity.¹

At 52 weeks, participants switching to orforglipron maintained their prior weight loss, with an average difference of 0.9 kg for individuals who switched from semaglutide and 5.0 kg for those from tirzepatide.¹

"ATTAIN‑MAINTAIN showed that orforglipron, a once-daily oral GLP-1, helped people maintain the weight they worked hard to lose. Participants in this study were able to switch directly from the highest tolerated doses of available injectable therapies onto oral doses of orforglipron,” Custer emphasized.¹

The company has submitted a new drug application to the FDA for orforglipron for the treatment of adults with obesity or overweight, following these data.¹

REFERENCES

1. Lilly's orforglipron helped people maintain weight loss after switching from injectable incretins to oral GLP-1 therapy in first-of-its-kind Phase 3 trial. News release. Eli Lilly and Company. December 18, 2025. Accessed December 22, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-orforglipron-helped-people-maintain-weight-loss-after

2. 2. A Study of Orforglipron for the Maintenance of Body Weight Reduction in Participants Who Have Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-MAINTAIN). Eli Lilly and Company. Updated December 22, 2025. Accessed December 22, 2025. https://clinicaltrials.gov/study/NCT06584916

3. A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5). Eli Lilly and Company. Updated November 26, 2025. Accessed December 22, 2025. https://clinicaltrials.gov/study/NCT05822830