Overview
- Helmholtz Munich researchers built a GLP-1/GIP peptide that carries the PPAR drug lanifibranor into cells, and in obese mice it cut weight and improved blood sugar more than semaglutide and GLP-1/GIP therapy.
- The conjugate latches onto incretin receptors, is taken into the cell, then a pH shift releases lanifibranor to turn on PPAR switches in the nucleus at about 6,900-fold lower exposure than prior mouse dosing.
- In the mouse tests, gut side effects looked similar to existing incretin drugs, and the team saw no signs of fluid buildup or anemia in the measures they reported.
- Genetic or drug blockades of GLP-1, GIP, or PPAR signals weakened the benefits, yet experts caution rodent models can inflate results and GIP receptors differ in humans, so clinical trials are needed.
- Separate work from Richard DiMarchi and Matthias Tschöp found a GIPR:GCGR co-agonist drove weight loss without GLP-1, hinting at options for people who cannot tolerate GLP-1 drugs’ nausea and dose titration.