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Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial.

ABSTRACT: AIMS/INTRODUCTION: To assess the efficacy and safety of sitagliptin compared with ?-glucosidase inhibitors in Japanese patients with type 2 diabetes inadequately controlled by metformin or pioglitazone alone. MATERIALS AND METHODS: In the present multicenter, randomized, open-label, parallel-group, active-controlled, non-inferiority trial, 119 patients aged 20-79 years with type 2 diabetes who had glycated hemoglobin 6.9-8.8% on stable metformin (500-1,500 mg/day) or pioglitazone (15-30 mg/day) alone were randomly assigned (1:1) to receive the addition of sitagliptin (50 mg/day) or an ?-glucosidase inhibitor (0.6 mg/day voglibose or 150 mg/day miglitol) for 24 weeks. The primary end-point was change in glycated hemoglobin from baseline to week 12. All data were analyzed according to the intention-to-treat principle. RESULTS: After 12 weeks, reductions in adjusted mean glycated hemoglobin from baseline were -0.70% in sitagliptin and -0.21% in the ?-glucosidase inhibitor groups respectively; between-group difference was -0.49% (95% confidence interval -0.66 to -0.32, P < 0.0001), meeting the predefined non-inferiority criterion (0.25%) and showing statistical significance. This statistical significance also continued after 24 weeks. Although sitagliptin did not affect bodyweight, ?-glucosidase inhibitors decreased bodyweight significantly from baseline (-0.39 kg; P = 0.0079). Gastrointestinal disorders were significantly lower with sitagliptin than with an ?-glucosidase inhibitor (6 [10.3%] patients vs 23 [39.7%]; P = 0.0003). Minor hypoglycemia occurred in two patients (3.5%) in each group. CONCLUSIONS: Sitagliptin showed greater efficacy and better tolerability than an ?-glucosidase inhibitor when added to stable doses of metformin or pioglitazone. These findings support the use of sitagliptin in Japanese patients with type 2 diabetes inadequately controlled by insulin-sensitizing agents. This trial was registered with UMIN (no. 000004675).

SUBMITTER: Yokoh H

PROVIDER: S-EPMC4364853 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial.

Yokoh Hidetaka H Kobayashi Kazuki K Sato Yasunori Y Takemoto Minoru M Uchida Daigaku D Kanatsuka Azuma A Kuribayashi Nobuichi N Terano Takashi T Hashimoto Naotake N Sakurai Kenichi K Hanaoka Hideki H Ishikawa Ko K Onishi Shunichiro S Yokote Koutaro K

Journal of diabetes investigation 20140924 2

<h4>Aims/introduction</h4>To assess the efficacy and safety of sitagliptin compared with α-glucosidase inhibitors in Japanese patients with type 2 diabetes inadequately controlled by metformin or pioglitazone alone.<h4>Materials and methods</h4>In the present multicenter, randomized, open-label, parallel-group, active-controlled, non-inferiority trial, 119 patients aged 20-79 years with type 2 diabetes who had glycated hemoglobin 6.9-8.8% on stable metformin (500-1,500 mg/day) or pioglitazone (1 ...[more]

PMID: 25802726

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Project description:OBJECTIVE:To assess the effectiveness of sitagliptin compared to sulfonylureas as add-on to metformin in adults with type 2 diabetes mellitus from both randomised controlled trials (RCTs) and 'real-world' non-randomised studies. METHODS AND ANALYSES:We conducted a systematic review of EMBASE, MEDLINE, CENTRAL and grey literature for RCTs and non-randomised studies. We reported outcomes relating to change in HbA1c, fasting glucose, weight, blood pressure and lipids from baseline and need for treatment change. No study investigating macrovascular and microvascular diabetes complications was found. Meta-analysis was used where studies were sufficiently homogenous. RESULTS:Seven RCTs and five non-randomised studies were eligible for inclusion from 1335 articles retrieved. Meta-analysis of three homogenous RCTs revealed a statistically significant decrease in weight with sitagliptin when compared to sulfonylureas (weighted mean difference (WMD) -2.05?kg; 95%?CI -2.38 to -1.71); however, a similar change from baseline in HbA1c (WMD 0.05; 95%?CI -0.03 to 0.12), fasting glucose (WMD 0.11; 95%?CI -0.08 to -0.29), blood pressure, lipids and the proportion achieving HbA1c <7% by study end (OR 0.98; 95%?CI 0.85 to 1.13) was observed.Non-randomised studies identified consisted of four prospective and one retrospective cohort study. Three of these five studies were of moderate/high quality, and results though less precise suggested similar real-world comparative glycaemic and weight effectiveness for both treatments. Data from two cohort studies suggested that treatment change (HR 0.65; 95%?CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95%?CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging. CONCLUSION:Sitagliptin users experienced modest weight loss compared to gain with sulfonylureas; however, this difference was around 2?kg, which may not be of major clinical significance for most individuals. Similar change was observed across most other effectiveness outcomes reported. Further studies are needed to address longer-term effectiveness outcomes for sitagliptin compared to sulfonylureas as add-on to metformin. PROSPERO REGISTRATION NUMBER:CRD42016033983.

Project description:Background:We previously reported the effect of sitagliptin or glimepiride treatment for 24 weeks on body composition in Japanese overweight and obese patients with type 2 diabetes. Although the degree of HbA1c reduction was similar between the two groups, significant reduction of intrahepatic lipid (IHL), determined by proton magnetic resonance spectroscopy (1H-MRCP), and fat mass (FM), determined by dual-energy X-ray absorptiometry (DXA), was observed in the sitagliptin group but not in the glimepiride group. As both IHL and FM are known as associating factors of insulin resistance, these reductions may lead to improvement of insulin sensitivity, which in turn may contribute to sitagliptin-induced amelioration of glycemic control. On the other hand, muscle and muscle/fat ratio were also reported to be positively correlated with insulin sensitivity, but we did not evaluate these factors. Methods:DXA separates the whole body into three major components, bone mass (BM), FM and fat and bone-free mass (FBFM), and measures the weight of each component. FBFM is normally used as a good marker of muscle mass; therefore, in this post-hoc analysis, we investigated whether sitagliptin treatment for 24 weeks influenced the FBFM and FBFM/FM ratio. Results:After 24 weeks, the FBFM and FBFM/FM ratio significantly increased in the sitagliptin group (47.6 ± 10.3 to 48.8 ± 11.0 kg, P < 0.05 and 2.0 ± 0.8 to 2.1 ± 0.8, P < 0.05), but not in the glimepiride group (49.7 ± 10.6 to 49.3 ± 9.9, P = 0.655 and 2.1 ± 0.9 to 2.0 ± 0.7, P = 0.855). The mean change of FBFM and FBFM/FM ratio from baseline to 24 weeks in the sitagliptin and glimepiride groups was 1.24 ± 2.01 (sitagliptin group) vs. -0.34 ± 2.63 kg (glimepiride group) (P = 0.074) and 0.13 ± 0.17 (sitagliptin group) vs. -0.11 ± 0.30 (glimepiride group) (P < 0.05), respectively. Conclusions:Sitagliptin 24-week treatment demonstrated not only reduction of body fat and liver fat but also an increase of muscle and muscle/fat ratio. These changes may partly explain the mechanism underlining sitagliptin-induced improvement of glycemic control.

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