Structure's GLP-1 pill shows 'injectable-like efficacy' in a mid-stage obesity study

Structure Therapeutics said Monday that its once-daily GLP-1 pill, aleniglipron, helped patients lose up to 16.2% of their body weight in an extended phase 2 obesity trial, marking the highest weight loss outcome reported to date for an oral version of the drug class.

If these results are confirmed in phase 3 testing, aleniglipron could raise the efficacy bar for oral obesity drugs by outperforming approved and investigational competitors in weight loss and tolerability.

The mid-stage Access 2 trial enrolled 85 adults with obesity or overweight with at least one weight-related condition. The researchers tested three doses of aleniglipron (120, 180, and 240 mg). After 44 weeks, participants receiving the highest dose achieved an average weight loss of 15%. Those given the 180 mg dose lost slightly more, reaching a 15.3% reduction in body weight.

The 120 mg dose led to 13.6% weight loss after 44 weeks in the Access 2 study and reached 16.2% at 56 weeks in an open-label extension study. Structure said that the weight loss results in both studies showed no signs of plateauing, indicating the possibility of achieving even greater weight loss in future testing.

Aleniglipron continues to show a tolerability profile similar to that of other GLP-1 drugs, Structure reported. Notably, only one participant (3.7%) taking Structure's experimental pill in the Access 2 study discontinued treatment due to side effects between weeks 28 and 44.

Like other GLP-1 receptor agonists, nausea and vomiting were the most commonly reported side effects, particularly during the dose escalation phase. However, interim tolerability data through February 20, 2026, indicates that starting with a lower dose of Structure's drug reduces adverse-event-related discontinuations during the titration phase.

At a median follow-up of 20 weeks, discontinuation rates due to side effects were 2% in the extension study and 3.4% in the aleniglipron arm of the body composition study, Structure highlighted.

"The totality of efficacy and tolerability data across the phase 2 program continues to demonstrate clear differentiation of aleniglipron, with the highest weight loss observed for an oral GLP-1 receptor agonist to date and a safety profile appropriate for chronic use in a disease that impacts millions of people," Structure CEO, Raymond Stevens, Ph.D., said.

These findings, along with previously reported mid-stage data, "reaffirm aleniglipron's potential to be a best-in-class oral GLP-1, with injectable-like efficacy," Stevens added.

Structure said an end-of-phase meeting with the FDA is scheduled for next quarter and confirmed that phase 3 development is on track to begin in the second half of the year.

So far, pharma giant Novo Nordisk is the first and only company to bring an oral GLP-1 to market, but top rival Eli Lilly could be next.

Earlier this year, Novo rolled out an oral version of its blockbuster weight loss drug, Wegovy. In a phase 3 trial, the 25 mg pill achieved an average weight loss of 13.6% over 64 weeks. Eli Lilly's contender orforglipron, which is currently awaiting FDA approval, reached 10.5% weight loss at 72 weeks using the highest 36 mg dose.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.