Effects of Vildagliptin vs. Sitagliptin on Blood Glucose Fluctuations (2017) PDF

2017, 64 (4), 417-424 Original Effects of 50 mg vildagliptin twice daily vs. 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose Hiroshi Nomoto*, Kimihiko Kimachi*, Hideaki Miyoshi, Hiraku Kameda, Kyu Yong Cho, Akinobu Nakamura, So Na...

2017, 64 (4), 417-424 Original Effects of 50 mg vildagliptin twice daily vs. 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose Hiroshi Nomoto*, Kimihiko Kimachi*, Hideaki Miyoshi, Hiraku Kameda, Kyu Yong Cho, Akinobu Nakamura, So Nagai, Takuma Kondo and Tatsuya Atsumi Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan Abstract. To date, several clinical trials have compared differences in glucose fluctuation observed with dipeptidyl peptidase-4 inhibitor treatment in patients with type 2 diabetes mellitus. However, most patients were assessed for limited periods or during hospitalization. The aim of the present study was to evaluate the effects of switching from sitagliptin to vildagliptin, or vice versa, on 12-week glucose fluctuations using self-monitoring of blood glucose in the standard care setting. We conducted a multicenter, prospective, open-label controlled trial in Japanese patients with type 2 diabetes. Thirty-two patients were treated with vildagliptin (50 mg) twice daily or sitagliptin (50 mg) once daily and were allocated to one of two groups: vildagliptin treatment for 12 weeks before switching to sitagliptin for 12 weeks, or vice versa. Daily profiles of blood glucose were assessed several times during each treatment period, and the mean amplitude of glycemic excursions and M-value were calculated. Metabolic biomarkers such as hemoglobin A1c (HbA1c), glycated albumin, and 1,5-anhydroglucitol were also assessed. With vildagliptin treatment, mean amplitude of glycemic excursions was significantly improved compared with sitagliptin treatment (57.9 ± 22.2 vs. 68.9 ± 33.0 mg/dL; p=0.0045). M-value (p=0.019) and mean blood glucose (p=0.0021) were also lower with vildagliptin, as were HbA1c, glycated albumin, and 1,5-anhydroglucitol. There were no significant differences in other metabolic parameters evaluated. Reduction of daily blood glucose profile fluctuations by vildagliptin was superior to that of sitagliptin in Japanese patients with type 2 diabetes. Key words: Blood glucose fluctuation, DPP-4 inhibitors, Type 2 diabetes mellitus ONE MATTER to be resolved in patients with type several anti-diabetic chemical agents are adminis- 2 diabetes mellitus (T2DM) is prevention of cardio- tered based on patient diabetic status, hypoglyce- vascular disease (CVD); there is a markedly high inci- mic drugs that can suppress the risk of CVD are lim- dence of CVD compared with those without diabetes ited. For these reasons, anti-diabetic agents that exert. Hyperglycemia and other metabolic risk factors anti-atherosclerotic effects would be beneficial. It has have been reported to contribute to this risk elevation recently been reported that fluctuation in blood glu- [2-4]. Although comprehensive care of risk factors cose levels is closely related to endothelial cell dam- for CVD includes glycemic control as well as treat- age , which is the first stage of atherosclerosis. It is ment of hypertension, hyperlipidemia, and hyperuri- therefore important to control not only glycemic sur- cemia, the rate of mortality remains higher in patients rogate markers (including glycosylated hemoglobin with diabetes. Therefore, prevention and improve- A1c [HbA1c]) but also glycemic variability to prevent ment of atherosclerosis are as important as maintain- CVD. Although some hypoglycemic agents have been ing favorable blood glucose conditions. Although used to manage glycemic fluctuation, dipeptidyl pep- Submitted Nov. 9, 2016; Accepted Dec. 30, 2016 as EJ16-0546 tidase-4 (DPP-4) inhibitors are frequently prescribed Released online in J-STAGE as advance publication Mar. 3, 2017 because of their glucose level-dependent hypoglyce- Correspondence to: Hideaki Miyoshi, Division of Rheumatology, mic mechanism and safety profile. These drugs not Endocrinology and Nephrology, Hokkaido University Graduate only improve HbA1c and glycemic control, but also School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. E-mail: [email protected] are expected to have anti-atherosclerotic and β-cell * Both authors contributed equally to this work. protective effects [7-9]. Although DPP-4 inhibitors ©The Japan Endocrine Society 418 Nomoto et al. differ in structure, metabolism, potency and half-life and 2 hours after each meal, and at bedtime) once , differences in clinical outcomes have not yet every 1 or 2 weeks for 12 weeks. After the 12-week been fully elucidated. Therefore, we compared differ- period, DPP-4 inhibitors were switched (sitagliptin 50 ences in glucose fluctuation for two DPP-4 inhibitors, mg once daily to vildagliptin 50 mg twice daily, and sitagliptin and vildagliptin, in long-term ambulatory vice versa) and treatment proceeded for an additional care using self-monitoring of blood glucose (SMBG). 12 weeks. SMBG samples were obtained from the fin- ger and measured using a One Touch Ultra blood glu- Materials and Methods cose meter (Johnson & Johnson, New Brunswick, NJ, USA). The accuracy for this system has been reported Study population and produced coefficients of variation of