A potential challenger to established GLP-1 therapies may offer a more convenient alternative to oral semaglutide. The ACHIEVE-3 study, funded by Eli Lilly, suggests that the novel compound orforglipron may offer superior glycaemic control and weight reduction compared with the current market leader.
Efficacy in head-to-head comparison
The international trial, which has spanned 131 research centres and included 1,698 participants with type 2 diabetes, sought to determine if orforglipron could surpass the benchmark set by oral semaglutide. After one year, participants treated with orforglipron achieved an average weight loss of 8%, higher than the 5% observed in the oral semaglutide cohort. Furthermore, the drug demonstrated greater improvements in blood sugar management and cardiometabolic risk factors.
In a press release, Kenneth Custer, Executive Vice President and President, Lilly Cardiometabolic Health, said: “The results of ACHIEVE-3 highlight the potential advantages of orforglipron over oral semaglutide for type 2 diabetes.”
Simplifying administration and adherence
A significant differentiator for orforglipron is its pharmacokinetic profile, which does not require the strict fasting windows associated with oral semaglutide. This simplified administration could provide a strategic advantage in the pharmaceutical market by improving long-term patient compliance.
However, the trial also highlights challenges regarding tolerability. Approximately 10% of participants discontinued the drug due to gastrointestinal adverse events, compared with 5% for oral semaglutide.
Future outlook for oral GLP-1s
While orforglipron faces higher participant discontinuation rates, its potentially superior efficacy suggests it could become a frontline therapy once it receives regulatory approval from organisations such as the FDA or EMA.
“With global submissions underway and FDA action on obesity expected next quarter, we’re focused on making this option available as quickly as possible,” emphasised Custer.
As the industry moves toward more convenient delivery systems, orforglipron is also being evaluated for a use case in cardiovascular health, potentially further broadening its clinical utility beyond diabetes and obesity management.
