An experimental daily pill that mimics the effects of injectable weight-loss drugs helped adults with obesity or overweight lose as much as 12.1% of their body weight over 36 weeks, according to results from a mid-stage clinical trial. The drug, aleniglipron, is a small-molecule GLP-1 receptor agonist taken orally rather than injected, and its developer says the results are the strongest yet reported for a pill in its class.
The phase 2b trial, published in Nature Medicine, enrolled 230 adults with obesity or overweight and at least one weight-related health condition at medical centers across the United States. Participants, whose average age was 50, were randomly assigned to take aleniglipron once daily at one of three doses — 45, 90 or 120 milligrams — or a placebo, with doses increased gradually over the 36-week treatment period. Average body weight fell 9.0% in the low-dose group, 10.7% at the middle dose and 12.1% at the highest dose, compared with just 0.5% among those on placebo; at the top dose, 86% of participants lost at least 5% of their body weight and 70% lost at least 10%.
How it compares
Aleniglipron, developed by Structure Therapeutics, activates only the GLP-1 receptor, unlike Eli Lilly's tirzepatide, which also targets a second hormone receptor called GIP. Its results are broadly in the range of injectable GLP-1 drugs such as semaglutide, sold as Wegovy and Ozempic, though direct head-to-head comparisons have not yet been run. The main advantage its developer is emphasizing is convenience: a pill avoids the syringes, needles and cold-chain storage that injectable GLP-1 drugs require, which could widen access in places where refrigeration or injection compliance is a barrier.
As with other drugs in the GLP-1 class, side effects were mostly gastrointestinal — nausea, vomiting, diarrhea and constipation were the most common — and were concentrated in the early dose-escalation phase. Just over 10% of participants across the active-treatment groups discontinued the drug because of side effects, and no cases of drug-induced liver injury were reported. Researchers noted they saw no clear plateau in weight loss through more than a year of continued therapy in an extension of the study, which they called an encouraging signal for longer-term use.
It could be taken with or without food, and you can potentially combine them with other medications.
Dr. Robert Kushner, Northwestern Medicine, on a practical advantage of an oral GLP-1 drug
The company has an end-of-phase-2 meeting scheduled with the U.S. Food and Drug Administration to finalize the design of a phase 3 program, which it expects to begin in the second half of this year. That larger trial is expected to test a slower dose-escalation strategy, starting at a lower titration dose, to improve tolerability. If phase 3 results hold up, aleniglipron would still need to clear a full efficacy and safety review before any approval, a process that typically takes several years from the start of late-stage testing.
