Anti-diabetic treatment regulates pro-fibrotic TGF-β serum levels in type 2 diabetics

BACKGROUND The single-center, open-label, four-arm, exploratory study investigates the relation of different anti-diabetics to serum levels of active TGF-β, a known pro-fibrotic stimulus, before and after a defined test meal. FINDINGS We investigated sera of patients with type 2 diabetes mellitus (T2DM) treated with metformin and sulfonylurea, insulin glargine or a DPP-4 inhibitor (DPP4i). Patients' sera were analyzed before and 5 h after a defined test meal at intervals of 30 min.The sulfonylurea/metformin group exhibited the highest basal levels of active TGF-β (31.50 ± 3.58 ng/ml). The glargine/metformin group had active TGF-β levels (24.98 ± 1.90 ng/ml) that were comparable to those of the healthy participants (22.12 ± 2.34 ng/ml). The lowest basal levels of active TGF-β were detected in the DPP-4i/metformin group (12.28 ± 0.84 ng/ml). Following the intake of a standardized meal, active TGF-β levels decreased (approx. 30%) in healthy subjects as well as in the sulfonylurea/metformin group and in the glargine/metformin group. After 5 h, the active TGF-β levels were normalized to basal levels. Active TGF-β levels in the DPP-4i/metformin group did not change significantly after the test meal. Overall plasma levels of insulin and proinsulin were comparable between healthy participants, and T2DM patients in the glargin/metformin group and in the DPP4i/metformin group. However, no correlation between active TGF-β levels, glucose, insulin or pro-insulin levels was detected. CONCLUSIONS T2DM patients often exhibit elevated levels of pro-fibrotic active TGF-β. Our results suggest that glargine/metformin and DPP4i/metformin treatment may more effectively reduce active TGF-β serum levels than the sulfonylurea/metformin treatment.