ArticleBMC pregnancy and childbirth2026
Comparison of the permeability of DPP-4 inhibitors-sitagliptin, vildagliptin, linagliptin, and alogliptin-in placental barrier cell models and exploration of their transport mechanisms by LC-MS/MS.
Article in BMC pregnancy and childbirth, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundUncontrolled hyperglycemia in pregnancy poses risks to both mother and fetus, but treatment options are limited. Sitagliptin, vildagliptin, linagliptin, and alogliptin are dipeptidyl peptidase-4 (DPP-4) inhibitors effective in type 2 diabetes. However, data on their placental transfer and safety in pregnant women is lacking. Therefore, this study compared the permeability of these drugs in multiple placental cell models, including BeWo, HTR-8/SVneo, and primary human trophoblast cells, and attempted to explore their transport mechanisms.
methodsA cost-effective liquid chromatography-tandem mass spectrometry method was developed and validated to quantify the four DPP-4 inhibitors. The accumulation of these drugs in placental cell models was compared, and the BeWo Transwell transport assay was conducted to assess transport rates. Transporter inhibitors, siRNA knockdown, and transporter overexpression cell models were used to explore the transmembrane transport mechanism of these drugs.
resultsLinagliptin had the highest accumulation in placental cells, followed by alogliptin, sitagliptin, and vildagliptin. The apparent permeability coefficient of linagliptin, alogliptin and sitagliptin was similar in BeWo cells, while vildagliptin was the lowest. The accumulation of linagliptin, alogliptin, sitagliptin and vildagliptin in BeWo cells at 37 °C were significantly higher than those at 4 °C, indicating the presence of carrier-mediated uptake. However, studies using transporter inhibitors, siRNA knockdown, and transporter overexpression cell models showed that equilibrative nucleoside transporters (ENTs), concentrative nucleoside transporters (CNTs), and organic anion transporter (OAT) 4 do not facilitate the placental transfer of linagliptin, alogliptin, sitagliptin, and vildagliptin.
conclusionsVildagliptin had the lowest accumulation and permeability in placental cells among the four DPP-4 inhibitors. There might be carrier-mediated transmembrane transport of linagliptin, alogliptin, sitagliptin and vildagliptin, but ENTs, CNTs and OAT4 were not involved in. This study provides a basis for future research on their safety during pregnancy.
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