- Email: [email protected]
Safety and efficacy of adding sitagliptin to insulin in patients with type 2 diabetes: The ASSIST-K study
diabetes research and clinical practice 103 (2014) e30–e33
Contents available at ScienceDirect
Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
Brief report
Safety and efficacy of adding sitagliptin to insulin in patients with type 2 diabetes: The ASSIST-K study Masahiko Takai a, Masashi Ishikawa a, Hajime Maeda a, Akira Kanamori a, Akira Kubota a, Hikaru Amemiya a, Takashi Iizuka a, Kotaro Iemitsu a, Tomoyuki Iwasaki a, Goro Uehara a, Shinichi Umezawa a, Mitsuo Obana a, Hideaki Kaneshige a, Mizuki Kaneshiro a, Takehiro Kawata a, Nobuo Sasai a, Tatsuya Saito a, Tetsuo Takuma a, Hiroshi Takeda a, Keiji Tanaka a, Nobuaki Tsurui a, Shigeru Nakajima a, Kazuhiko Hoshino a, Shin Honda a, Hideo Machimura a, Kiyokazu Matoba a, Fuyuki Minagawa a, Nobuaki Minami a, Yukiko Miyairi a, Atsuko Mokubo a, Tetsuya Motomiya a, Manabu Waseda a, Masaaki Miyakawa a, Yoshikazu Naka a, Yasuo Terauchi b, Yasushi Tanaka c, Ikuro Matsuba a,* a
The Study Group of the Diabetes Committee, Kanagawa Physicians Association, Kanagawa, Japan Department of Endocrinology and Metabolism, Yokohama City University, Kanagawa, Japan c Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kanagawa, Japan b
article info
abstract
Article history:
We retrospectively studied more than 1000 patients with type 2 diabetes attending 36
Received 6 September 2013
Japanese clinics to investigate the efficacy and safety of adding sitagliptin to various insulin
Received in revised form
regimens. We found that the treatment with add-on sitagliptin for 6-months was effective,
6 September 2013
irrespective of the type or dose of concomitant insulin.
Accepted 26 December 2013
# 2014 Elsevier Ireland Ltd. All rights reserved.
Available online 6 January 2014 Keywords: Type 2 diabetes Sitagliptin Insulin Glycemic control
* Corresponding author at: Matsuba Medical Clinic, 2-159 Tsukagoshi, Saiwai-ward, Kawasaki-city, Kanagawa 212-0024, Japan. Tel.: +81 44 522 1678; fax: +81 44 522 1698. E-mail address: [email protected] (I. Matsuba). 0168-8227/$ – see front matter # 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2013.12.045
e31
diabetes research and clinical practice 103 (2014) e30–e33
1.
Introduction
3.
Although patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy usually have a long duration of disease and a reduced insulin secretory capacity, their characteristics vary. In the real clinical setting, a variety of insulin regimens are employed to treat T2DM along with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. However, there have been few reports on the usefulness of such strategies [1–4], and studies need to be done to investigate the safety and efficacy of combined treatment with sitagliptin and various insulin regimens in a large patient population. We addressed these issues by performing a study at 36 diabetes clinics.
2.
Research design and methods
This retrospective multicenter study enrolled outpatients with T2DM who had inadequate glycemic control despite receiving insulin and were treated with add-on sitagliptin therapy from November 2011 to March 2013. Their glycemic control, insulin dose, concomitant drugs, body weight, laboratory parameters, and adverse events were analyzed. All the patients enrolled had received insulin therapy for at least 6 months before starting add-on sitagliptin, had a hemoglobin A1c (HbA1c) 7.0%, and were followed for 6 months after the start of combined treatment. Results are reported as the mean standard deviation. All analyses were performed using SPSS version 19 (SPSS Inc., Chicago, IL, USA). The effect of sitagliptin treatment was assessed by one-way analysis of variance (ANOVA) and statistical significance was accepted at p < 0.05. This study was approved by the Ethics Committee of the Kanagawa Physicians Association, and was registered with the Clinical Trials Registry (http://clinicaltrials.gov; NCT01855087).
Results
A total of 1004 patients were analyzed after excluding 53 patients who received add-on sitagliptin for less than 6 months, 81 patients with an HbA1c <7.0%, and 30 patients with incomplete data. Assessment of baseline characteristics revealed that HbA1c was 8.7 1.3%. At baseline, the patients’ age was 63.9 12.1 years, with a body mass index (BMI) of 25.5 4.6. The mean duration of insulin was 6.3 5.6 years, the mean daily dose of insulin was 32.0 23.1 units, and 41.8% (n = 418) of the patients were on insulin monotherapy. The concomitant diabetes medications were as follows: sulfonylureas (SUs, 22.2%), biguanides (39.7%), thiazolidinediones (6.4%), and aglucosidase inhibitors (18.4%). The initial dose of sitagliptin (50 mg) was not changed in most of the patients (80.9%, n = 809). HbA1c was significantly reduced from 8.7 1.3% to 8.3 1.2% ( p < 0.05) after 1 month of sitagliptin combination therapy, while it declined to 8.0 1.3% both at 3 months and 6 months (both p < 0.05) after the start of therapy. Mean body weight increased slightly by 0.1 kg ( p < 0.05). The dosages of insulin and oral drugs other than sitagliptin were not changed. In the long-acting and once-daily insulin group, the mixed and twice-daily insulin group, the mixed or rapid-acting and 3 times daily insulin group, and the basal-bolus group (Table 1), HbA1c was reduced by 1.1%, 0.7%, 0.7%, and 0.6%, respectively (Fig. 1). The percent reduction of HbA1c was significantly greater in the long-acting and once-daily insulin group than in the other three insulin groups ( p < 0.05). When we divided the long-acting and once-daily insulin group into two subgroups, which were patients treated with SUs (n = 134) and those not (n = 81), there was no significant difference in the percent reduction of HbA1c between the two subgroups. We also analyzed 160 patients in whom blood C-peptide was measured before starting sitagliptin and divided them into three groups; however, there was no significant difference with regard to the percent reduction of HbA1c among these groups.
Table 1 – Baseline characteristics of the four insulin therapy groups.
Age (years) Gender (male/female) Body mass index Hemoglobin A1c (%) Fasting blood glucose (mmol/L) Blood C-peptide (nmol/L) Duration of diabetes (years) Duration of insulin therapy (years) Insulin dose (units) Concomitant drugs Sulfonylureas Biguanides Thiazolidinediones a-Glucosidase inhibitors No concomitant drugs * **
One-way analysis of variance (ANOVA). Fisher’s exact test.
Long-acting, once-daily (n = 215)
Mixed, twice-daily (n = 162)
65.5 12.2 112/103 24.4 4.4 9.0 1.5 180.9 74.1 1.9 1.1 (n = 40) 15.1 10.1 3.6 5.3 10.7 7.2
66.5 11.5 90/72 24.8 4.1 8.4 1.2 192.0 82.9 1.8 1.2 (n = 20) 18.0 8.6 7.3 5.8 27.0 13.2
134 (62.3%) 88 (40.9%) 21 (9.8%) 36 (16.7%) 47 (21.8%)
20 67 11 36 70
(12.3%) (41.4%) (6.8%) (22.2%) (43.1%)
Three times daily (no long-acting insulin) (n = 209)
Basal-bolus (n = 334)
p value
63.7 11.4 107/102 25.8 4.7 8.8 1.2 192.1 67.0 1.4 1.0 (n = 40) 18.7 9.4 6.9 6.0 37.4 19.9
61.8 12.7 177/157 26.6 4.6 8.7 1.3 179.5 66.2 1.2 0.9 (n = 60) 16.6 8.1 7.3 5.0 46.2 24.8
<0.001* 0.860** <0.001* <0.001* 0.723* 0.003*
20 (9.6%) 81 (38.8%) 12 (5.7%) 50 (23.9%) 104 (49.0%)
21 (6.3%) 128 (38.3%) 15 (4.5%) 50 (15.0%) 166 (48.8%)
<0.001** 0.883** 0.098** 0.034** <0.001**
0.001* <0.001* <0.001*
e32
diabetes research and clinical practice 103 (2014) e30–e33
Fig. 1 – Changes of HbA1c after the start of add-on sitagliptin therapy stratified by the insulin regimen.
Multiple regression analysis showed that a higher baseline HbA1c level was the main factor contributing to HbA1c reduction. Hypoglycemia symptoms, none of them severe, occurred in 7.4% of all patients. The frequency of hypoglycemia did not differ among the insulin regimens.
4.
Discussion
To the best of our knowledge, this study is the first to confirm the combined effect of sitagliptin and intensive insulin therapy, and it demonstrated an HbA1c-lowering effect of add-on sitagliptin with any insulin regimen. In the basal-bolus group and the lower C-peptide group, in which endogenous insulin secretion may be impaired, the reduction of HbA1c was mainly due to other effects of sitagliptin rather than its influence on insulin secretion. Usefulness of DPP-4 inhibitors for patients with type 1 diabetes on insulin therapy [5] and an inhibitory effect of glucagon-like peptide-1 (GLP-1) receptor agonists on glucagon secretion in patients with type 1 diabetes [6] have been reported. An inhibitory effect on glucagon secretion may have contributed to the improvement of HbA1c with add-on sitagliptin therapy. Our stratified analysis showed that although all regimens were effective, HbA1c was reduced more in the long-acting and once-daily insulin group than in the other groups. This result may be explained by some differences of baseline characteristics, but the duration of insulin therapy or combined use of SUs was not relevant and the C-peptide level also showed no differences. It has been reported that both BMI and endogenous insulin secretion are lower in T2DM patients from East Asia than in
patients from Western countries [7], and that sitagliptin is more effective in Japanese patients [8]. Observational studies performed in Japan have revealed that sitagliptin is more effective for patients with a lower BMI [9,10]. Further studies are needed to clarify the potential influence of racial factors. This study had some limitations. First, it was a retrospective investigation. Second, we did not assess all of variables that could have contributed to HbA1c reduction, including markers of b-cell function and the basal level of active GLP-1. Nonetheless, our findings demonstrated that adding sitagliptin to insulin therapy was useful in T2DM patients with poor glycemic control, irrespective of the insulin regimen.
Conflict of interest The authors declare that there are no conflicts of interest to declare.
Acknowledgments The authors would like to thank the members of the Kanagawa Physicians Association. The authors also thank Shogo Ito, Yoshio Aoyagi, Yasuyuki Jin, Taro Asakura, Kazuaki Shinoda and Hideki Aizawa for their efforts in enrolling patients in the study. This research, entitled ‘‘A Study of Safety and Efficacy of Sitagliptin Added to Insulin Therapy in the Treatment of Type 2 Diabetes in Kanagawa (ASSIST-K),’’ was conducted by the Diabetes Task Force of the Kanagawa Physicians Association and was supported by the Kidney Foundation, Japan.
diabetes research and clinical practice 103 (2014) e30–e33
references [6] [1] Vilsbøll T, Rosenstock J, Yki-Ja¨rvinen H, Cefalu WT, Chen Y, Luo E, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab 2010;12:167–77. [2] Kadowaki T, Tajima N, Odawara M, Minamide T, Kawashima M, Yanagida D, et al. Efficacy and safety of sitagliptin add-on therapy in Japanese patients with type 2 diabetes on insulin monotherapy. Diabetol Int )2013;(March) [Epub ahead of print]. [3] Hong ES, Khang AR, Yoon JW, Kang SM, Choi SH, Park KS, et al. Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study. Diabetes Obes Metab 2012;14(9):795–802. [4] Katsuno T, Ikeda H, Ida K, Miyagawa JI, Namba M. Add-on therapy with the DPP-4 inhibitor sitagliptin improves glycemic control in insulin-treated Japanese patients with type 2 diabetes mellitus. Endocr J )2013;(February) [Epub ahead of print]. [5] Ellis SL, Moser EG, Snell-Bergeon JK, Rodionova AS, Hazenfield RM, Garg SK. Effect of sitagliptin on glucose control in adult patients with Type 1 diabetes: a pilot,
[7]
[8]
[9]
[10]
e33
double-blind, randomized, crossover trial. Diabet Med 2011;28(10):1176–81. Kielgast U, Krarup T, Holst JJ, Madsbad S. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diabetes Care 2011;34(7):1463–8. Matsuba I, Saito K, Takai M, Hirao K, Sone H. Japan diabetes clinical data management study group fasting insulin levels and metabolic risk factors in type 2 diabetic patients at the first visit in Japan: a 10-year, nationwide, observational study (JDDM 28). Diabetes Care 2012;35(9):1853–7. Park H, Park C, Kim Y, Rascati KL. Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: meta-analysis. Ann Pharmacother 2012;46(11): 1453–69. Maeda H, Kubota A, Tanaka Y, Terauchi Y, Matsuba I. ASSET-K Study group. The safety, efficacy and predictors for HbA1c reduction of sitagliptin in the treatment of Japanese type 2 diabetes. Diabetes Res Clin Pract 2012;95(1):e20–2. Kubota A, Maeda H, Kanamori A, Matoba K, Jin Y, Minagawa F, et al. Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients. J Clin Med Res 2012;4(5):309–13.
Contents available at ScienceDirect
Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
Brief report
Safety and efficacy of adding sitagliptin to insulin in patients with type 2 diabetes: The ASSIST-K study Masahiko Takai a, Masashi Ishikawa a, Hajime Maeda a, Akira Kanamori a, Akira Kubota a, Hikaru Amemiya a, Takashi Iizuka a, Kotaro Iemitsu a, Tomoyuki Iwasaki a, Goro Uehara a, Shinichi Umezawa a, Mitsuo Obana a, Hideaki Kaneshige a, Mizuki Kaneshiro a, Takehiro Kawata a, Nobuo Sasai a, Tatsuya Saito a, Tetsuo Takuma a, Hiroshi Takeda a, Keiji Tanaka a, Nobuaki Tsurui a, Shigeru Nakajima a, Kazuhiko Hoshino a, Shin Honda a, Hideo Machimura a, Kiyokazu Matoba a, Fuyuki Minagawa a, Nobuaki Minami a, Yukiko Miyairi a, Atsuko Mokubo a, Tetsuya Motomiya a, Manabu Waseda a, Masaaki Miyakawa a, Yoshikazu Naka a, Yasuo Terauchi b, Yasushi Tanaka c, Ikuro Matsuba a,* a
The Study Group of the Diabetes Committee, Kanagawa Physicians Association, Kanagawa, Japan Department of Endocrinology and Metabolism, Yokohama City University, Kanagawa, Japan c Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kanagawa, Japan b
article info
abstract
Article history:
We retrospectively studied more than 1000 patients with type 2 diabetes attending 36
Received 6 September 2013
Japanese clinics to investigate the efficacy and safety of adding sitagliptin to various insulin
Received in revised form
regimens. We found that the treatment with add-on sitagliptin for 6-months was effective,
6 September 2013
irrespective of the type or dose of concomitant insulin.
Accepted 26 December 2013
# 2014 Elsevier Ireland Ltd. All rights reserved.
Available online 6 January 2014 Keywords: Type 2 diabetes Sitagliptin Insulin Glycemic control
* Corresponding author at: Matsuba Medical Clinic, 2-159 Tsukagoshi, Saiwai-ward, Kawasaki-city, Kanagawa 212-0024, Japan. Tel.: +81 44 522 1678; fax: +81 44 522 1698. E-mail address: [email protected] (I. Matsuba). 0168-8227/$ – see front matter # 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2013.12.045
e31
diabetes research and clinical practice 103 (2014) e30–e33
1.
Introduction
3.
Although patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy usually have a long duration of disease and a reduced insulin secretory capacity, their characteristics vary. In the real clinical setting, a variety of insulin regimens are employed to treat T2DM along with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. However, there have been few reports on the usefulness of such strategies [1–4], and studies need to be done to investigate the safety and efficacy of combined treatment with sitagliptin and various insulin regimens in a large patient population. We addressed these issues by performing a study at 36 diabetes clinics.
2.
Research design and methods
This retrospective multicenter study enrolled outpatients with T2DM who had inadequate glycemic control despite receiving insulin and were treated with add-on sitagliptin therapy from November 2011 to March 2013. Their glycemic control, insulin dose, concomitant drugs, body weight, laboratory parameters, and adverse events were analyzed. All the patients enrolled had received insulin therapy for at least 6 months before starting add-on sitagliptin, had a hemoglobin A1c (HbA1c) 7.0%, and were followed for 6 months after the start of combined treatment. Results are reported as the mean standard deviation. All analyses were performed using SPSS version 19 (SPSS Inc., Chicago, IL, USA). The effect of sitagliptin treatment was assessed by one-way analysis of variance (ANOVA) and statistical significance was accepted at p < 0.05. This study was approved by the Ethics Committee of the Kanagawa Physicians Association, and was registered with the Clinical Trials Registry (http://clinicaltrials.gov; NCT01855087).
Results
A total of 1004 patients were analyzed after excluding 53 patients who received add-on sitagliptin for less than 6 months, 81 patients with an HbA1c <7.0%, and 30 patients with incomplete data. Assessment of baseline characteristics revealed that HbA1c was 8.7 1.3%. At baseline, the patients’ age was 63.9 12.1 years, with a body mass index (BMI) of 25.5 4.6. The mean duration of insulin was 6.3 5.6 years, the mean daily dose of insulin was 32.0 23.1 units, and 41.8% (n = 418) of the patients were on insulin monotherapy. The concomitant diabetes medications were as follows: sulfonylureas (SUs, 22.2%), biguanides (39.7%), thiazolidinediones (6.4%), and aglucosidase inhibitors (18.4%). The initial dose of sitagliptin (50 mg) was not changed in most of the patients (80.9%, n = 809). HbA1c was significantly reduced from 8.7 1.3% to 8.3 1.2% ( p < 0.05) after 1 month of sitagliptin combination therapy, while it declined to 8.0 1.3% both at 3 months and 6 months (both p < 0.05) after the start of therapy. Mean body weight increased slightly by 0.1 kg ( p < 0.05). The dosages of insulin and oral drugs other than sitagliptin were not changed. In the long-acting and once-daily insulin group, the mixed and twice-daily insulin group, the mixed or rapid-acting and 3 times daily insulin group, and the basal-bolus group (Table 1), HbA1c was reduced by 1.1%, 0.7%, 0.7%, and 0.6%, respectively (Fig. 1). The percent reduction of HbA1c was significantly greater in the long-acting and once-daily insulin group than in the other three insulin groups ( p < 0.05). When we divided the long-acting and once-daily insulin group into two subgroups, which were patients treated with SUs (n = 134) and those not (n = 81), there was no significant difference in the percent reduction of HbA1c between the two subgroups. We also analyzed 160 patients in whom blood C-peptide was measured before starting sitagliptin and divided them into three groups; however, there was no significant difference with regard to the percent reduction of HbA1c among these groups.
Table 1 – Baseline characteristics of the four insulin therapy groups.
Age (years) Gender (male/female) Body mass index Hemoglobin A1c (%) Fasting blood glucose (mmol/L) Blood C-peptide (nmol/L) Duration of diabetes (years) Duration of insulin therapy (years) Insulin dose (units) Concomitant drugs Sulfonylureas Biguanides Thiazolidinediones a-Glucosidase inhibitors No concomitant drugs * **
One-way analysis of variance (ANOVA). Fisher’s exact test.
Long-acting, once-daily (n = 215)
Mixed, twice-daily (n = 162)
65.5 12.2 112/103 24.4 4.4 9.0 1.5 180.9 74.1 1.9 1.1 (n = 40) 15.1 10.1 3.6 5.3 10.7 7.2
66.5 11.5 90/72 24.8 4.1 8.4 1.2 192.0 82.9 1.8 1.2 (n = 20) 18.0 8.6 7.3 5.8 27.0 13.2
134 (62.3%) 88 (40.9%) 21 (9.8%) 36 (16.7%) 47 (21.8%)
20 67 11 36 70
(12.3%) (41.4%) (6.8%) (22.2%) (43.1%)
Three times daily (no long-acting insulin) (n = 209)
Basal-bolus (n = 334)
p value
63.7 11.4 107/102 25.8 4.7 8.8 1.2 192.1 67.0 1.4 1.0 (n = 40) 18.7 9.4 6.9 6.0 37.4 19.9
61.8 12.7 177/157 26.6 4.6 8.7 1.3 179.5 66.2 1.2 0.9 (n = 60) 16.6 8.1 7.3 5.0 46.2 24.8
<0.001* 0.860** <0.001* <0.001* 0.723* 0.003*
20 (9.6%) 81 (38.8%) 12 (5.7%) 50 (23.9%) 104 (49.0%)
21 (6.3%) 128 (38.3%) 15 (4.5%) 50 (15.0%) 166 (48.8%)
<0.001** 0.883** 0.098** 0.034** <0.001**
0.001* <0.001* <0.001*
e32
diabetes research and clinical practice 103 (2014) e30–e33
Fig. 1 – Changes of HbA1c after the start of add-on sitagliptin therapy stratified by the insulin regimen.
Multiple regression analysis showed that a higher baseline HbA1c level was the main factor contributing to HbA1c reduction. Hypoglycemia symptoms, none of them severe, occurred in 7.4% of all patients. The frequency of hypoglycemia did not differ among the insulin regimens.
4.
Discussion
To the best of our knowledge, this study is the first to confirm the combined effect of sitagliptin and intensive insulin therapy, and it demonstrated an HbA1c-lowering effect of add-on sitagliptin with any insulin regimen. In the basal-bolus group and the lower C-peptide group, in which endogenous insulin secretion may be impaired, the reduction of HbA1c was mainly due to other effects of sitagliptin rather than its influence on insulin secretion. Usefulness of DPP-4 inhibitors for patients with type 1 diabetes on insulin therapy [5] and an inhibitory effect of glucagon-like peptide-1 (GLP-1) receptor agonists on glucagon secretion in patients with type 1 diabetes [6] have been reported. An inhibitory effect on glucagon secretion may have contributed to the improvement of HbA1c with add-on sitagliptin therapy. Our stratified analysis showed that although all regimens were effective, HbA1c was reduced more in the long-acting and once-daily insulin group than in the other groups. This result may be explained by some differences of baseline characteristics, but the duration of insulin therapy or combined use of SUs was not relevant and the C-peptide level also showed no differences. It has been reported that both BMI and endogenous insulin secretion are lower in T2DM patients from East Asia than in
patients from Western countries [7], and that sitagliptin is more effective in Japanese patients [8]. Observational studies performed in Japan have revealed that sitagliptin is more effective for patients with a lower BMI [9,10]. Further studies are needed to clarify the potential influence of racial factors. This study had some limitations. First, it was a retrospective investigation. Second, we did not assess all of variables that could have contributed to HbA1c reduction, including markers of b-cell function and the basal level of active GLP-1. Nonetheless, our findings demonstrated that adding sitagliptin to insulin therapy was useful in T2DM patients with poor glycemic control, irrespective of the insulin regimen.
Conflict of interest The authors declare that there are no conflicts of interest to declare.
Acknowledgments The authors would like to thank the members of the Kanagawa Physicians Association. The authors also thank Shogo Ito, Yoshio Aoyagi, Yasuyuki Jin, Taro Asakura, Kazuaki Shinoda and Hideki Aizawa for their efforts in enrolling patients in the study. This research, entitled ‘‘A Study of Safety and Efficacy of Sitagliptin Added to Insulin Therapy in the Treatment of Type 2 Diabetes in Kanagawa (ASSIST-K),’’ was conducted by the Diabetes Task Force of the Kanagawa Physicians Association and was supported by the Kidney Foundation, Japan.
diabetes research and clinical practice 103 (2014) e30–e33
references [6] [1] Vilsbøll T, Rosenstock J, Yki-Ja¨rvinen H, Cefalu WT, Chen Y, Luo E, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab 2010;12:167–77. [2] Kadowaki T, Tajima N, Odawara M, Minamide T, Kawashima M, Yanagida D, et al. Efficacy and safety of sitagliptin add-on therapy in Japanese patients with type 2 diabetes on insulin monotherapy. Diabetol Int )2013;(March) [Epub ahead of print]. [3] Hong ES, Khang AR, Yoon JW, Kang SM, Choi SH, Park KS, et al. Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study. Diabetes Obes Metab 2012;14(9):795–802. [4] Katsuno T, Ikeda H, Ida K, Miyagawa JI, Namba M. Add-on therapy with the DPP-4 inhibitor sitagliptin improves glycemic control in insulin-treated Japanese patients with type 2 diabetes mellitus. Endocr J )2013;(February) [Epub ahead of print]. [5] Ellis SL, Moser EG, Snell-Bergeon JK, Rodionova AS, Hazenfield RM, Garg SK. Effect of sitagliptin on glucose control in adult patients with Type 1 diabetes: a pilot,
[7]
[8]
[9]
[10]
e33
double-blind, randomized, crossover trial. Diabet Med 2011;28(10):1176–81. Kielgast U, Krarup T, Holst JJ, Madsbad S. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diabetes Care 2011;34(7):1463–8. Matsuba I, Saito K, Takai M, Hirao K, Sone H. Japan diabetes clinical data management study group fasting insulin levels and metabolic risk factors in type 2 diabetic patients at the first visit in Japan: a 10-year, nationwide, observational study (JDDM 28). Diabetes Care 2012;35(9):1853–7. Park H, Park C, Kim Y, Rascati KL. Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes: meta-analysis. Ann Pharmacother 2012;46(11): 1453–69. Maeda H, Kubota A, Tanaka Y, Terauchi Y, Matsuba I. ASSET-K Study group. The safety, efficacy and predictors for HbA1c reduction of sitagliptin in the treatment of Japanese type 2 diabetes. Diabetes Res Clin Pract 2012;95(1):e20–2. Kubota A, Maeda H, Kanamori A, Matoba K, Jin Y, Minagawa F, et al. Pleiotropic effects of sitagliptin in the treatment of type 2 diabetes mellitus patients. J Clin Med Res 2012;4(5):309–13.