Study: DPP4 Inhibitors Yield Promise for Systemic Sclerosis Treatment

Further Investigations of DPP4 Inhibitors

Dr. Soare notes that the potent antifibrotic effects of DPP4 inhibitors may have direct translational implications. DPP4 inhibitors have already been shown to have a good tolerability and safety profile, making them an attractive target for clinical investigation. In 2006, the U.S. Food and Drug Admini­stration approved the use of oral DPP4 inhibitors to treat type 2 diabetes. DPP4 inhibitors increase the levels of active insulinotropic polypeptide and glucagon-like peptide-1, resulting in stimulation of insulin and inhibition of glucagon.⁶ Data from other clinical studies has shown promising results for DPP4 inhibitors in other disease states, such as renal disease.⁷

“To prove the effect in patients with systemic sclerosis, it would definitely be interesting to test DPP4 inhibitors in a clinical trial,” says Dr. Soare. “Using the data from the post-marketing studies available in patients with type 2 diabetes treated with DPP4 inhibitors would speed up the process of approval of these agents for another indication.”

DPP4 inhibitors are not the only components of the TGF-β pathway that researchers have pursued. In 2015, researchers reported promising results of a phase 2 trial of systemic sclerosis patients with freso­limumab, an inhibitor of all three isoforms of TGF-β.⁸ Dr. Soare points out that in contrast to fresolimumab, inhibiting DPP4 expression would not affect all downstream signaling pathways of TGF-β. This might make it more suitable for use in light of its side effect profile.

Clinical trials are needed before any strong conclusions can be drawn. However, DPP4 inhibitors may represent a new avenue of hope for this devastating disease.

Ruth Jessen Hickman, MD, is a graduate of the Indiana University School of Medicine. She is a freelance medical and science writer living in Bloomington, Ind.

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