Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus

Yagi, Shusuke; Aihara, Ken‐ichi; Akiyama, Masashi; Fukuda, Daiju; Salim, Hotimah Masdan; Ishida, Masaharu; Matsuura, Tomomi; Ise, Takayuki; Yamaguchi, Koji; Igarashi, Takashi; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Matsumoto, Toshio; Sata, Masataka

doi:10.4093/dmj.2015.39.4.342

Cited by 17 publications

(16 citation statements)

References 19 publications

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“…There was a greater improvement in glycemic control in Japanese patients with more hyperglycemia (higher HbA1c, FPG and 2h‐PMG) at baseline, compared with those having lesser degrees of hyperglycemia. These findings confirm and extend previous reports that Japanese patients with type 2 diabetes and higher baseline glycemic status will experience greater absolute benefit from treatment with sitagliptin than those with lower baseline glycemic status. They are also in agreement with analyses showing that in many studies outside Japan assessing the efficacy of a variety of antihyperglycemic agents, high baseline HbA1c correlates with greater reduction from baseline after treatment.…”

Section: Discussionsupporting

confidence: 91%

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Factors associated with the glucose‐lowering efficacy of sitagliptin in Japanese patients with type 2 diabetes mellitus: Pooled analysis of Japanese clinical trials

Tajima

Eiki

Okamoto

et al. 2019

J of Diabetes Invest

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Aims/Introduction: To explore the factors associated with the glucose-lowering efficacy of sitagliptin treatment in Japanese patients with type 2 diabetes mellitus. Materials and Methods: This was a post-hoc analysis of pooled data from seven sitagliptin phase II and III clinical studies carried out in Japan. All studies were double-blind, randomized, placebo-controlled, parallel-group and of 12-week duration. The analysis population consisted of 1,075 type 2 diabetes mellitus patients. In two of the trials, sitagliptin 50 mg and/or 100 mg daily were used as monotherapy; in five others, sitagliptin 50 mg daily was used as add-on treatment to ongoing pioglitazone, glimepiride, metformin, voglibose or glinides. Efficacy (reduction in hemoglobin A1c [HbA1c]) was evaluated in 12 sets of subgroups defined by demographic, glycemic, pancreatic b-cell function and insulin resistance parameters. An analysis of covariance model was used to evaluate the interaction between each parameter and efficacy. Results: Sitagliptin consistently provided a clinically meaningful reduction in HbA1c relative to placebo across all subgroups. Within subgroups, a greater absolute HbA1c reduction was associated with higher baseline HbA1c, fasting plasma glucose and 2-h post-meal glucose. Lower b-cell function, represented by homeostatic model assessment of b-cell function and insulinogenic index, was also associated with greater HbA1c reduction. In contrast, age, sex, body mass index, duration of type 2 diabetes mellitus and insulin resistance-related parameters did not interact with HbA1c changes. Conclusions: Sitagliptin treatment was associated with clinically meaningful improvement in glycemic control in all subgroups of Japanese patients with type 2 diabetes mellitus that were evaluated. Higher baseline glycemic status and lower baseline b-cell function were identified as factors associated with greater HbA1c reduction after sitagliptin treatment. † Present address: Otemachi PLACE Medical Clinic, Tokyo, Japan. ‡ These authors contributed equally to the work.

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Section: Discussionsupporting

confidence: 91%

“…Several reports suggest that the glucose‐lowering efficacy of DPP4is is reduced in Japanese and East Asian patients with higher BMI. A significant correlation between BMI and HbA1c reduction in Asian‐dominant subgroups was also observed in a meta‐analysis.…”

Section: Discussionmentioning

confidence: 64%

Factors associated with the glucose‐lowering efficacy of sitagliptin in Japanese patients with type 2 diabetes mellitus: Pooled analysis of Japanese clinical trials

Tajima

Eiki

Okamoto

et al. 2019

J of Diabetes Invest

View full text Add to dashboard Cite

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“…30,31 It is a common consent that baseline HbA1c level is a predictor of response to DPP-4 inhibitors, but BMI had been rarely reported as a positive association. 22 Yagi et al reported low baseline BMI as a predictor of efficacy in Japanese patients, 14 the same as in our study in Taiwanese patients, which means that baseline BMI is a unique predictor for Asian patients treated with DPP-4 inhibitors.…”

Section: Discussionsupporting

confidence: 86%

“…High baseline HbA1c level was the most significant predictor for effective efficacy (△HbA1c ≥0.5%) of DPP-4 inhibitors in Taiwanese patients with T2D. For a higher baseline HbA1c level with a greater reduction in HbA1c, our study focused on its role in effective efficacy (△HbA1c ≥0.5%) and provided Taiwanese patient-level data, consistent with previous studies of other countries, which were described by Nomiyama et al, 12 Maeda et al, 13 and Yagi et al 14 Furthermore, Esposito et al reported the meta-regression of a 0.26% greater reduction in HbA1c with every increase of 1% of baseline HbA1c, a response to DPP-4 inhibitors. 15 Little is known on this subject, but it is clear that a baseline HbA1c level is the most readily identifiable predictor of response to most antidiabetic drugs.…”

Section: Discussionsupporting

confidence: 85%

<p>Predictors of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Taiwanese Patients with Type 2 Diabetes Mellitus</p>

Lin

Huang

2019

DMSO

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Background/purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors are the most popular oral antidiabetic drugs (OADs) in recent 20 years because of the low risk of hypoglycemia, intermediate efficacy to lower glycated hemoglobin (△HbA1c): 0.5-0.9%, neutral effect on body weight change, convenience for usage (mostly once daily), and rare occurrence of major side effects. The purpose of this study was to determine the important predictors of the efficacy of naïve use of DPP-4 inhibitors in Taiwanese patients with type 2 diabetes mellitus (T2D). Methods: A retrospective observational study was conducted. Of the T2D patients, 193 (122 men) naïve DPP-4 inhibitor users with an age of 58.0 ± 12.6 years, disease duration 5.4 ± 4.7 years, body mass index (BMI) 26.1 ± 4.3 kg/m 2 , and estimated glomerular filtration rate 95.9 ± 27.0 mL/min/1.73M 2 were assessed for △HbA1c in 6 months. Results: After 6 months of DPP-4 inhibitors use, mostly second or third line of OADs (2.8 ± 0.7 kinds of OADs), 193 T2D patients (mean baseline HbA1c: 8.4 ± 1.4%) had △HbA1c 1.1 ± 1.2% on average (P < 0.01). The group with a higher baseline HbA1c level had more effective efficacy (△HbA1c ≥0.5%) in lowering HbA1c. Single regression analysis showed that the change in HbA1c after 6 months of treatment was positively associated with the baseline HbA1c level (R = 0.71, P < 0.001). In addition, multiple regression analysis showed that contributors to decrease HbA1c level after 6 months were high baseline HbA1c level, low BMI, short T2D duration, and fewer kinds of OADs. Conclusion: Our study suggested that high baseline HbA1c level, low BMI, short T2D duration, and fewer kinds of OADs are the predictors of the efficacy of DPP-4 inhibitors in Taiwanese patients with T2D. The baseline HbA1c level, in particular, played the most important role in effective efficacy (△HbA1c ≥0.5%).

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“…Moreover, as reported by Jones et al [18], the addition of rosiglitazone to metformin was most effective in obese, insulin-resistant patients with type 2 diabetes. In DPP-4 inhibitors treated patients, two studies in Japanese patients [19] and in Korean T2DM subjects [20] suggested that DPP-4 inhibitor treatment efficacy was associated with a low baseline BMI. In GLP-1 receptor agonists treated patients, a study designed to identify predictors of response to liraglutide therapy in Japanese patients [21] concluded that the efficacy of liraglutide could be associated with BMI at baseline.…”

Section: Discussionmentioning

confidence: 99%

Baseline Body Mass Index and the Efficacy of Hypoglycemic Treatment in Type 2 Diabetes: A Meta-Analysis

et al. 2016

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AimThe aim of this study is to compare the effects of hypoglycemic treatments in groups of patients categorized according to the mean baseline body mass indexes (BMIs).MethodsStudies were identified by a literature search and all the studies were double blind, placebo-controlled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. The electronic search was first conducted in January 2015 and repeated in June 2015.Results227 studies were included. Treatment with sulfonylureas was compared with placebo in overweight patients and resulted in a significantly greater change in the HbA1c levels (weighted mean difference (WMD), −1.39%) compared to obese patients (WMD, −0.77%)(p<0.05). Treatment with metformin in overweight patients resulted in a comparable change in the HbA1c levels (WMD, −0.99%) compared to obese patients (WMD, −1.06%)(p>0.05). Treatment with alpha glucosidase inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.94%) that was comparable that in overweight (WMD, −0.72%) and obese patients (WMD, −0.56%)(p>0.05). Treatment with thiazolidinediones in normal weight patients was associated with a HbA1c change (WMD, −1.04%) that was comparable with that in overweight (WMD, −1.02%) and obese patients (WMD, −0.88%)(p>0.05). Treatment with DPP-4 inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.93%) that was comparable with that in overweight (WMD, −0.66%) and obese patients (WMD, −0.61%)(p>0.05). In total, of the seven hypoglycemic agents, regression analysis indicated that the mean baseline BMI was not associated with the mean HbA1c changes from baseline.ConclusionIn each kind of hypoglycemic therapy in type 2 diabetes, the baseline BMI was not associated with the efficacy of HbA1c changes from baseline.

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Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus

Cited by 17 publications

References 19 publications

Factors associated with the glucose‐lowering efficacy of sitagliptin in Japanese patients with type 2 diabetes mellitus: Pooled analysis of Japanese clinical trials

Factors associated with the glucose‐lowering efficacy of sitagliptin in Japanese patients with type 2 diabetes mellitus: Pooled analysis of Japanese clinical trials

<p>Predictors of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Taiwanese Patients with Type 2 Diabetes Mellitus</p>

Baseline Body Mass Index and the Efficacy of Hypoglycemic Treatment in Type 2 Diabetes: A Meta-Analysis

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