lessthanhalf
Explorer
A study that came out in Nature yesterday: https://www.nature.com/articles/s41586-026-10427-5
What they did was take lanifibranor, a small molecule PPARα/γ/δ agonist currently in phase 3 trials for metabolic dysfunction-associated steatohepatitis, and attach it to a GLP-1 - GIP agonist peptide. The result was substantially greater weight loss than with the GLP-1 - GIP peptide by itself. Since the lanifibranor is tethered to the peptide, cells carrying GLP-1 receptors take it up preferentially, which means it can act at doses 1/6000th of those used in the phase 3 trials of the drug on its own. That matters because the molecule alone comes with side effects. It also permits precise targeting of the molecule to cells expressing GLP-1 or GIP.
In mice, weight loss came close to twice what something similar to tirzepatide produces, or nearly 40%. The fact that lanifibranor is already in phase 3 could move things along somewhat. Human trials are not quite on the horizon, since they are not fully confident they understand all the effects of PPARα/γ/δ agonism, even though the drug is in phase 3 trials?
Given where the research stands, this will not happen for a good while yet, but I would not be surprised if the same basic idea gets tried again with different small molecules linked to glp-1 peptides down the line.
What they did was take lanifibranor, a small molecule PPARα/γ/δ agonist currently in phase 3 trials for metabolic dysfunction-associated steatohepatitis, and attach it to a GLP-1 - GIP agonist peptide. The result was substantially greater weight loss than with the GLP-1 - GIP peptide by itself. Since the lanifibranor is tethered to the peptide, cells carrying GLP-1 receptors take it up preferentially, which means it can act at doses 1/6000th of those used in the phase 3 trials of the drug on its own. That matters because the molecule alone comes with side effects. It also permits precise targeting of the molecule to cells expressing GLP-1 or GIP.
In mice, weight loss came close to twice what something similar to tirzepatide produces, or nearly 40%. The fact that lanifibranor is already in phase 3 could move things along somewhat. Human trials are not quite on the horizon, since they are not fully confident they understand all the effects of PPARα/γ/δ agonism, even though the drug is in phase 3 trials?
Given where the research stands, this will not happen for a good while yet, but I would not be surprised if the same basic idea gets tried again with different small molecules linked to glp-1 peptides down the line.
