Structure Touts 16% Weight Loss for Aleniglipron, Calling It the Most Effective Oral GLP-1 Yet

Structure Therapeutics announced topline results from its ACCESS clinical program on March 16, showing that its once-daily oral pill aleniglipron produced up to 16.3% placebo-adjusted weight loss at the 180 mg dose after 36 weeks. The company is calling it the highest efficacy reported for any oral GLP-1 receptor agonist to date, a claim that could shake up a competitive field where injectable drugs have long held the performance edge. For patients and investors watching the oral weight loss space, the numbers are hard to ignore.

The data come from two Phase 2 studies: ACCESS and ACCESS II. In the original ACCESS trial, which enrolled roughly 230 participants, three dose levels were tested over 36 weeks. The 120 mg group saw 12.1% absolute weight loss (11.3% placebo-adjusted), translating to about 27 pounds, while the 90 mg and 45 mg arms showed 10.7% and 9.0% absolute reductions, respectively. All results were statistically significant.

ACCESS II pushed higher with 120 mg, 180 mg, and 240 mg doses in approximately 85 participants. The standout numbers came from the 180 mg arm, which hit 13.3% absolute and 14.4% placebo-adjusted weight loss, while the 240 mg group landed close behind at 14.2% absolute and 15.3% placebo-adjusted - amounting to roughly 35.5 pounds lost. Notably, the placebo group in ACCESS II actually gained weight (+1.0%), which contributed to the larger placebo-adjusted figures compared to the original trial.

On the safety front, side effects tracked with what’s typical across the GLP-1 class. Nausea and vomiting were the most common complaints, particularly early in treatment, and discontinuation rates in the original ACCESS study averaged about 10.4% across active arms. The company highlighted that a slower titration starting at 2.5 mg, tested in a separate body composition study and an open-label extension, brought those discontinuation numbers down to zero at the initial dose levels - a meaningful tolerability improvement heading into Phase 3 design.

There were no cases of drug-induced liver injury, no persistent liver enzyme elevations, and no QTc prolongation, which Structure emphasized as evidence supporting the case for chronic use. Beyond weight, secondary outcomes from the ACCESS 120 mg arm included systolic blood pressure reductions of 6.4 to 7.5 mmHg and modest HbA1c improvements of 0.28% to 0.37%. Eighty-six percent of participants in the 120 mg group achieved at least 5% weight loss, while 70% hit the 10% threshold.

The oral GLP-1 space is heating up fast, and Structure’s data arrive at a pivotal moment. Novo Nordisk’s oral semaglutide won FDA approval earlier this year, marking a genuine shift for patients who prefer pills over injections, but its weight loss numbers have generally trailed those of injectable formulations. A 16% placebo-adjusted reduction puts aleniglipron in territory that starts to compete with injectables - which is exactly what pill-based treatments have been chasing, and what the company describes as “injectable-like efficacy.”

There’s still reason for caution, as Phase 2 trials are smaller and shorter than the pivotal studies needed for FDA approval. The GI side effects, while expected for this drug class, remain a practical concern for adherence at scale, and the weight loss curves in both ACCESS studies hadn’t plateaued by week 36. That plateau question cuts both ways - it’s encouraging that participants may not have hit their ceiling, but it also means the full picture of long-term efficacy and tolerability isn’t clear yet.

Structure Therapeutics has a Type B End-of-Phase 2 meeting with the FDA planned for the first half of 2026, and if that goes well, the company expects to start Phase 3 trials by mid-2026. The proposed Phase 3 design would use the slower 2.5 mg starting dose and evaluate doses up to 240 mg, directly incorporating the tolerability lessons from the open-label extension. CEO Raymond Stevens said aleniglipron delivered “clinically meaningful, competitive and dose-dependent weight loss with appropriate safety for chronic use” - the company will need to prove that in a larger, longer study, but for now the oral GLP-1 race has a new front-runner making its case.