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The acute efficacy and safety of dulaglutide in Japanese adults with type 2 Diabetes Mellitus
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211
the usual doses of drugs after consuming less than the normal amount of food (except during sick days). No cases of death were directly caused by hypoglycemia. Hospitalization was necessitated in 52.4% of all cases. Conclusions: We conclude that avoiding the onset of hypoglycemia and selecting target HbA1c levels and drugs according to the patient’s age and disease status should be prioritized. PD-58 The acute efficacy and safety of dulaglutide in Japanese adults with type 2 Diabetes Mellitus Asako MIZOGUCHI1*, Rui IMAMINE1, Minoru KUSAMA1, Hajime MASE1, Ai SATO1, Makiko MINATOGUCHI1, Atsuko WATARAI2, Takahiko KAWAMURA2, Nigishi HOTTA1, Eitaro NAKASHIMA1. 1Department of Diabetes and Endocrinology, Chubu Rosai Hospital, 2Research Center for the Promotion of Health and Employment Support, Chubu Rosai Hospital, Japan Background: Recently, many kinds of GLP-1 receptor agonist are widely used in clinical practices for improving glycemic control in patients with type 2 diabetes mellitus (DM). Dulaglutide is a novel weekly GLP-1 receptor agonist which came to Japanese market in October 2015 and is expected to have greater glucose and body weight (BW) lowering effect on patients with type 2 DM. In this study, we retrospectively investigated the efficacy and safety of dulaglutide in clinical practice. Method: Thirty-five patients with type 2 DM in our hospital who were administrated dulaglutide were enrolled from October 2015 to March 2016 consecutively. We observed up to 12 weeks in this study. We collected the clinical data of HbA1c and body weight every month through the study period. Also we investigated adverse side effects, i.e. hypoglycemia. Moreover, we conducted a questionnaire study about dulaglutide and its injection device after its administration. Results: Baseline characteristics are indicated thus; Male 22 patients (62.9%) Female 13 patients (37.1%). Age: male 64 years old, female 65 years old. HbA1c: 8.0%, BW: 68.9 kg. Before replacement or initiating dulaglutide, the 9 patients used other GLP-1 receptor agonist, the 13 patients used insulin. After 8 weeks, HbA1c in all the patients has decreased −0.45% ( p < 0.05, vs baseline). In only male after 4 weeks HbA1c has decreased −0.31% ( p < 0.05, vs baseline) After 8 weeks patients who added dulaglutide on insulin significantly improved HbA1c (−0.35% p < 0.05, vs baseline). BW significantly decreased in all patients after 4 weeks treatments (−0.52 kg p < 0.05, vs baseline) but not in 8 weeks. There were no reports of any severe hypoglycemia attack during study period. In the questionnaire in this study, 40% of the patients felt that they had better glycemic control and 40% of them felt they had lower frequency of hypoglycemia using dulaglutide than their previous therapy. All patients prefer weekly GLP-1 receptor agonist to daily one. Conclusion: In this study, dulaglutide improved glycemic control in Japanese type 2 DM patients in clinical practice. Furthermore, continuing to add the diabetes patients and extend the period of observation we are going to report this study. PD-59 Inhibition of central GSK3 regulates body weight and glucose metabolism Rie TAKAHASHI1, Licht MIYAMOTO1 *, Keisuke FUKUTA1, Koichiro TSUCHIYA1. 1Dept. of Medical Pharmacology, Inst. of Biomedical Sciences, Tokushima University, Japan Overweight and obesity lead to metabolic disorders like insulin resistance and hypertension, which related to development of type 2 diabetes, coronary heart disease and cancer with the increase of body mass index (BMI). The WHO statistics in 2014 shows that more than 2 billion people are overweight (BMI from 25 to 29.9), and more than
S109
half a billion are obese (BMI 30 or greater). This survey indicates that about one-third of the world’s population tends to be obese. GSK3 (glycogen synthase kinase 3) is a ubiquitous kinase and a downstream molecule of insulin signal pathway. Insulin regulates glucose homeostasis with increasing glucose uptake and storage. When it binds to the insulin receptor, glucose uptake is accelerated to promote the glycogen synthesis in the liver and skeletal muscle by GSK3 inactivation. In this mechanism, GSK3 can be a target for the development of treatment for type 2 diabetes, but its central action has not been understood yet. It has been demonstrated that central administration of insulin causes anorexigenic effect and leads to reduction of body weight. Therefore, we used GSK3 inhibitor to reveal significance of central GSK3 on metabolism and feeding behavior. All experiments were performed using 8- to 10-week-old male ddY mice. We administered vehicle (PBS) or a GSK3 inhibitor to the mice by ICV injection. The mice were housed individually under 12-hour day and night cycle. In a single dose, ICV administration was performed after 16 hours fast and then we measured the change in body weight, food intake and water consumption. Otherwise, as another experiment, repetitive administration was also performed for 10 days and we conducted ipGTT after 7days treatment. The single dose of GSK3 inhibitor led to reduction of body weight, food intake and water consumption. The continual administration of GSK3 inhibitor showed more striking effects. An ipGTT revealed that glucose tolerance tended to be improved in the mice administrated with GSK3 inhibitor in comparison to the control mice. The maximum glucose concentration in the GSK3 inhibited mice was lower than the other group. Recently, GSK3 inhibitors have been developed for medication of Alzheimer’s disease. Our results suggested that central GSK3 should be a new target to treat metabolic diseases, and GSK3 inhibitors would be novel anti-obesity agents having antidiabetic effect. PD-60 Factors related to diabetes’ ABC control in a Taipei community hospital – A prospective follow-up study Tong-Yuan TAI1 *, Yu-Kang CHANG2, Jiun-Yian LIN1, Pi-Yuan WONG1, I-Chuan LIN1, I-Ju LIEN1, Chung-Hsueh CHUNG1, Chih-Cheng HSU2. 1Taipei Jen-Chi Hospital, Taipei 2Institute of Population Health Sciences, National Health Research Institutes, Taiwan Background: The majority of diabetes patients in Taiwan have been cared in either community clinics or local hospitals; however, quality of diabetes control in community settings remains unclear. This study aimed at demonstrating performance of diabetes care and investigating factors that influenced ABC (HbA1c, blood pressure, and low-density lipoprotein cholesterol [LDL-C]) control in a community hospital in Taipei. Methods: We adopted the current status of ABC control in National Diabetes Health Promotion Centers in Taiwan, which have been regularly supervised and accredited by the Health Promotion Administration, as the performance indicators to evaluate quality of diabetes care in the investigated community hospital. Logistic regressions were used to identify significant factors related to diabetes’ ABC control. Results: Since 2006, the investigated community hospital has implemented a diabetes management program, strengthening dietetic consultation, health education, and case management. The data surveillance center has currently recorded 300 enrollees to this program. The percentage of good ABC control, including HbA1c < 7%, blood pressure <130/ 80 mmHg, and LDL-C < 100 mg/dL, one year after participating in the program was 40.7%, 33.7%, and 32.8%, respectively. Compared to the corresponding indicators in National
the usual doses of drugs after consuming less than the normal amount of food (except during sick days). No cases of death were directly caused by hypoglycemia. Hospitalization was necessitated in 52.4% of all cases. Conclusions: We conclude that avoiding the onset of hypoglycemia and selecting target HbA1c levels and drugs according to the patient’s age and disease status should be prioritized. PD-58 The acute efficacy and safety of dulaglutide in Japanese adults with type 2 Diabetes Mellitus Asako MIZOGUCHI1*, Rui IMAMINE1, Minoru KUSAMA1, Hajime MASE1, Ai SATO1, Makiko MINATOGUCHI1, Atsuko WATARAI2, Takahiko KAWAMURA2, Nigishi HOTTA1, Eitaro NAKASHIMA1. 1Department of Diabetes and Endocrinology, Chubu Rosai Hospital, 2Research Center for the Promotion of Health and Employment Support, Chubu Rosai Hospital, Japan Background: Recently, many kinds of GLP-1 receptor agonist are widely used in clinical practices for improving glycemic control in patients with type 2 diabetes mellitus (DM). Dulaglutide is a novel weekly GLP-1 receptor agonist which came to Japanese market in October 2015 and is expected to have greater glucose and body weight (BW) lowering effect on patients with type 2 DM. In this study, we retrospectively investigated the efficacy and safety of dulaglutide in clinical practice. Method: Thirty-five patients with type 2 DM in our hospital who were administrated dulaglutide were enrolled from October 2015 to March 2016 consecutively. We observed up to 12 weeks in this study. We collected the clinical data of HbA1c and body weight every month through the study period. Also we investigated adverse side effects, i.e. hypoglycemia. Moreover, we conducted a questionnaire study about dulaglutide and its injection device after its administration. Results: Baseline characteristics are indicated thus; Male 22 patients (62.9%) Female 13 patients (37.1%). Age: male 64 years old, female 65 years old. HbA1c: 8.0%, BW: 68.9 kg. Before replacement or initiating dulaglutide, the 9 patients used other GLP-1 receptor agonist, the 13 patients used insulin. After 8 weeks, HbA1c in all the patients has decreased −0.45% ( p < 0.05, vs baseline). In only male after 4 weeks HbA1c has decreased −0.31% ( p < 0.05, vs baseline) After 8 weeks patients who added dulaglutide on insulin significantly improved HbA1c (−0.35% p < 0.05, vs baseline). BW significantly decreased in all patients after 4 weeks treatments (−0.52 kg p < 0.05, vs baseline) but not in 8 weeks. There were no reports of any severe hypoglycemia attack during study period. In the questionnaire in this study, 40% of the patients felt that they had better glycemic control and 40% of them felt they had lower frequency of hypoglycemia using dulaglutide than their previous therapy. All patients prefer weekly GLP-1 receptor agonist to daily one. Conclusion: In this study, dulaglutide improved glycemic control in Japanese type 2 DM patients in clinical practice. Furthermore, continuing to add the diabetes patients and extend the period of observation we are going to report this study. PD-59 Inhibition of central GSK3 regulates body weight and glucose metabolism Rie TAKAHASHI1, Licht MIYAMOTO1 *, Keisuke FUKUTA1, Koichiro TSUCHIYA1. 1Dept. of Medical Pharmacology, Inst. of Biomedical Sciences, Tokushima University, Japan Overweight and obesity lead to metabolic disorders like insulin resistance and hypertension, which related to development of type 2 diabetes, coronary heart disease and cancer with the increase of body mass index (BMI). The WHO statistics in 2014 shows that more than 2 billion people are overweight (BMI from 25 to 29.9), and more than
S109
half a billion are obese (BMI 30 or greater). This survey indicates that about one-third of the world’s population tends to be obese. GSK3 (glycogen synthase kinase 3) is a ubiquitous kinase and a downstream molecule of insulin signal pathway. Insulin regulates glucose homeostasis with increasing glucose uptake and storage. When it binds to the insulin receptor, glucose uptake is accelerated to promote the glycogen synthesis in the liver and skeletal muscle by GSK3 inactivation. In this mechanism, GSK3 can be a target for the development of treatment for type 2 diabetes, but its central action has not been understood yet. It has been demonstrated that central administration of insulin causes anorexigenic effect and leads to reduction of body weight. Therefore, we used GSK3 inhibitor to reveal significance of central GSK3 on metabolism and feeding behavior. All experiments were performed using 8- to 10-week-old male ddY mice. We administered vehicle (PBS) or a GSK3 inhibitor to the mice by ICV injection. The mice were housed individually under 12-hour day and night cycle. In a single dose, ICV administration was performed after 16 hours fast and then we measured the change in body weight, food intake and water consumption. Otherwise, as another experiment, repetitive administration was also performed for 10 days and we conducted ipGTT after 7days treatment. The single dose of GSK3 inhibitor led to reduction of body weight, food intake and water consumption. The continual administration of GSK3 inhibitor showed more striking effects. An ipGTT revealed that glucose tolerance tended to be improved in the mice administrated with GSK3 inhibitor in comparison to the control mice. The maximum glucose concentration in the GSK3 inhibited mice was lower than the other group. Recently, GSK3 inhibitors have been developed for medication of Alzheimer’s disease. Our results suggested that central GSK3 should be a new target to treat metabolic diseases, and GSK3 inhibitors would be novel anti-obesity agents having antidiabetic effect. PD-60 Factors related to diabetes’ ABC control in a Taipei community hospital – A prospective follow-up study Tong-Yuan TAI1 *, Yu-Kang CHANG2, Jiun-Yian LIN1, Pi-Yuan WONG1, I-Chuan LIN1, I-Ju LIEN1, Chung-Hsueh CHUNG1, Chih-Cheng HSU2. 1Taipei Jen-Chi Hospital, Taipei 2Institute of Population Health Sciences, National Health Research Institutes, Taiwan Background: The majority of diabetes patients in Taiwan have been cared in either community clinics or local hospitals; however, quality of diabetes control in community settings remains unclear. This study aimed at demonstrating performance of diabetes care and investigating factors that influenced ABC (HbA1c, blood pressure, and low-density lipoprotein cholesterol [LDL-C]) control in a community hospital in Taipei. Methods: We adopted the current status of ABC control in National Diabetes Health Promotion Centers in Taiwan, which have been regularly supervised and accredited by the Health Promotion Administration, as the performance indicators to evaluate quality of diabetes care in the investigated community hospital. Logistic regressions were used to identify significant factors related to diabetes’ ABC control. Results: Since 2006, the investigated community hospital has implemented a diabetes management program, strengthening dietetic consultation, health education, and case management. The data surveillance center has currently recorded 300 enrollees to this program. The percentage of good ABC control, including HbA1c < 7%, blood pressure <130/ 80 mmHg, and LDL-C < 100 mg/dL, one year after participating in the program was 40.7%, 33.7%, and 32.8%, respectively. Compared to the corresponding indicators in National