1. Risk for Hospitalized Heart Failure Among New Users of Saxagliptin, Sitagliptin, and Other Antihyperglycemic Drugs: A Retrospective Cohort Study.
Toh, S., Hampp, C., Reichman, M.E., Graham, D.J., Balakrishnan, S., Pucino, F., Hamilton, J. , Lendle, S., Lyer, A., Rucker, M., Pimentel, M., Nathwani, N., Griffin, M.R., Brown, N.J. and Fireman, B.H., 2016. Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: a retrospective cohort study. Annals of internal medicine, 164(11), pp.705-714.
Recent postmarketing trials produced conflicting results about the risk for hospitalized heart failure (hHF) associated with dipeptidyl peptidase-4 (DPP-4) inhibitors, creating uncertainty about the safety of these antihyperglycemic agents.
2. Combined therapy with sitagliptin plus granulocyte-colony stimulating factor in patients with acute myocardial infarction - Long-term results of the SITAGRAMI trial
Gross, L., Theiss, H.D., Grabmaier, U., Adrion, C., Mansmann, U., Sohn, H.Y., Hoffmann, E., Steinbeck, G., Franz, W.M. and Brenner, C., 2016. Combined therapy with sitagliptin plus granulocyte-colony stimulating factor in patients with acute myocardial infarction - Long-term results of the SITAGRAMI trial. International journal of cardiology, 215, pp441-445.
Autologous progenitor cell therapy comprising granulocyte-colony stimulating factor (G-CSF) for mobilization of bone-marrow derived progenitor cells (BMPCs) into peripheral blood and inhibition of dipeptidylpeptidase-IV by sitagliptin for enhanced myocardial recruitment of circulating BMPCs has been shown to improve survival after acute myocardial infarction (MI) in preclinical studies. In the SITAGRAMI trial we found that during short-term follow-up G-CSF plus sitagliptin (GS) failed to show a beneficial effect on cardiac function and clinical events in patients with acute MI that underwent successful PCI. The objective of the present analysis was to assess the impact of GS versus placebo treatment on long-term clinical outcomes of the SITAGRAMI trial patient population.
3. Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase.
Tang, S. T., Su, H., Zhang, Q., Tang, H. Q., Wang, C. J., Zhou, Q., Wei, W., Zhu, H.Q. and Wang, Y., 2016. Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase. International journal of molecular medicine, 37(6), pp1558-1566.
Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors, including sitagliptin, exert favourable effects on the vascular endothelium. DPP-4 inhibitors suppress the degradation of glucagon-like peptide-1 (GLP‑1), which has been reported to enhance nitric oxide (NO) production. However, the effects of DPP-4 inhibitors on endothelin-1 (ET-1) expression in the aorta, as well as the underlying mechanisms responsible for these effects, have yet to be investigated in animal models of diabetes mellitus (DM). In the present study, the rats were randomly divided into the following four groups: i) control; ii) DM; iii) DM + low‑dose sitagliptin (10 mg/kg); and iv) DM + high‑dose sitagliptin (30 mg/kg). Apart from the control group, all the rats received a high-fat diet for 8 weeks prior to the induction of diabetes with an intraperitoneal injection of streptozotocin. The treatments were then administered for 12 weeks. The serum levels of ET-1, NO, GLP-1 and insulin were measured as well as endothelial function. The expression of ET-1, AMP-activated protein kinase (AMPK) and nuclear factor (NF)-κB/IκBα were determined. After 12 weeks of treatment, the diabetic rats receiving sitagliptin showed significantly elevated serum levels of GLP-1 and NO, and reduced levels of ET-1. Moreover, sitagliptin significantly attenuated endothelial dysfunction as well as the remodeling of the aortic wall. Notably, sitagliptin inhibited ET-1 expression at the transcriptional and translational level in the aorta, which may have been mediated by the suppression of the NF-κB/IκBα system induced by AMPK activation. The majority of the above-mentioned effects were dose dependent. Taken together, the findings of the present study indicate that sitagliptin inhibits ET-1 expression in the aortic endothelium by suppressing the NF-κB/IκBα system through the activation of the AMPK pathway in diabetic rats. These findings further demonstrate some of the vasoprotective properties of DPP-4 inhibitors in vivo.
4. Medium-Term Effect of Add-On Therapy with the DPP-4 Inhibitor, Sitagliptin, in Insulin-Treated Japanese Patients with Type 2 Diabetes Mellitus
Katsuno, T., Ikeda, H. and Namba, M., 2016. Medium-term effect of add-on therapy with the DPP-4 inhibitor, sitagliptin, in insulin-treated Japanese patients with type 2 diabetes mellitus. Diabetes Therapy, 7(2), pp309-320.
A 12-week prospective study was previously performed to assess the effect of add-on therapy with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in patients with type 2 diabetes mellitus (T2DM) receiving insulin treatment. Patients were followed until week 48 to investigate the medium-term efficacy and safety of the add-on therapy with sitagliptin.