Pleiotropic Effects of Sitagliptin in the Treatment of Type 2 Diabetes Mellitus Patients

Abstract

BackgroundSitagliptin is a DPP-4 inhibitor that became available for use in Japan three years ago. This study was conducted to identify the pleiotropic effects of sitagliptin other than blood glucose lowering in Japanese type 2 diabetes mellitus patients.MethodsA retrospective, observational study of 940 type 2 diabetes mellitus patients was conducted. The primary outcome measures were HbA1c, blood pressure, and lipid profiles measured at 0, 4, and 12 weeks of sitagliptin therapy.ResultsAfter 12 weeks of sitagliptin treatment, compared with baseline, HbA1c decreased 0.64% ± 0.86%; systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly; and serum creatinine (Cr) and uric acid (UA) levels were mildly but significantly elevated. A correlation analysis of the changes in systolic blood pressure, diastolic blood pressure, creatinine, and uric acid (ΔSBP, ΔDBP, ΔCr, ΔUA) from baseline to 12 weeks showed significant negative correlations between ΔSBP and ΔCr, ΔSBP and ΔUA, and ΔDBP and ΔCr. Total cholesterol and postprandial triglycerides were significantly decreased at both 4 and 12 weeks. Alkaline phosphatase (ALP) decreased significantly, and there was a significant positive correlation between changes in ALP and HbA1c.ConclusionsSitagliptin seems to be effective not only in lowering blood glucose but also in lowering blood pressure, lipid, and ALP levels. Sitagliptin appears to contribute to a Na-diuretic action due to GLP-1.

Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study

“…In the present study, sitagliptin did not cause any increase in the body mass index. Sitagliptin also decreases postprandial triglyceride level [27] and lowers blood pressure, blood lipid level [28] and alkaline phosphatase level [29]. Our present study also showed decreased systolic and diastolic blood pressures, decreased LDL-C level and decreased triglyceride levels, which is similar to results from previously published studies.…”

Effects of sitagliptin on the serum creatinine in Japanese type 2 diabetes

“…In a previous study, we showed elevation of Cr and a correlation between elevation of Cr and reduction of the blood pressure with sitagliptin [3]. The new finding is a correlation between elevation of Cr and reduction of HbA1c.…”

“…Among the 1332 patients enrolled in this study, 826 patients have been taking sitagliptin for 24 months and HbA1c <7.0% (<53 mmol/mol) was achieved in 387 patients (46%). A significant increase in Cr, albeit within normal limits, have been reported in clinical studies in Japan [3,5]. On the other hand, elevation of Cr level was not reported in any of the previous studies carried out to evaluate the influence of sitagliptin on the renal function, including meta-analyses conducted in Western countries [6,7].…”

“…The Group has additionally reported long-term maintenance of glycemic control in Japanese patients with type 2 diabetes receiving this drug [4]. Because of the observed significant elevation of serum creatinine (Cr) at 3 months after the start of sitagliptin treatment [3], the Group conducted the present study for a detailed evaluation of the long-term efficacy of treatment with sitagliptin, particularly its influence on the serum creatinine # 2015 Elsevier Ireland Ltd. All rights reserved.…”

“…The Kanagawa Diabetes Study Group has previously published clinical findings on the short-term efficacy, safety and pleiotropic effects of sitagliptin in large numbers of patients [1][2][3]. The Group has additionally reported long-term maintenance of glycemic control in Japanese patients with type 2 diabetes receiving this drug [4].…”