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

Akira Kubota, Hajime Maeda, Akira Kanamori, Kiyokazu Matoba, Yasuyuki Jin, Fuyuki Minagawa, Mitsuo Obana, Koutarou Iemitsu, Shogo Ito, Hikaru Amemiya, Mizuki Kaneshiro, Masahiko Takai, Hideaki Kaneshige, Kazuhiko Hoshino, Masashi Ishikawa, Nobuaki Minami, Tetsuo Takuma, Nobuo Sasai, Sachio Aoyagi, Takehiro Kawata, Atsuko Mokubo, Hiroshi Takeda, Shin Honda, Hideo Machimura, Tetsuya Motomiya, Manabu Waseda, Yoshikazu Naka, Yasushi Tanaka, Yasuo Terauchi, Ikuro Matsuba

Abstract


Background: Sitagliptin 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.

Methods: A 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.

Results: After 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.

Conclusions: Sitagliptin 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.




doi: http://dx.doi.org/10.4021/jocmr1061w


Keywords


Diabetes mellitus; GLP-1; Lipids; Sitagliptin; Pleiotropic effects

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