Carmegliptin

To study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC).

DPPIV expression in EC cells was detected by flow cytometry, reverse transcription‐polymerase chain reaction analysis and Western blot. Interleukin‐6 (IL‐6) expression in the supernatant was measured by enzyme‐linked immunosorbent assay. The protein levels of signal transducers and activators of transcription‐3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit‐8 assay was used to determine the half‐maximal inhibitory concentration of sitagliptin.

Overexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL‐6/STAT3 signaling pathway, and that IL‐6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001).

DPPIV enhances the properties that allow tumorigenesis in EC via IL‐6 and STAT3 signaling.

Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested.

To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD.

We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion.

7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 [95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation.

Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.