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Safety and efficacy comparison of different insulin regimens in T2DM patients: A meta-analysis
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211
PJ-12 Comparisons of placebo effect of hypoglycemic drugs between Asian and Caucasian type 2 diabetes patients Xiaoling CAI1 *, Lingli ZHOU1, Wenjia YANG1, Xueyao HAN1, Linong JI1. 1Peking University People’s Hospital, China Aim: It was hypothesis that the placebo effect might be different between different ethnicity. The aim of this study is to compare the placebo effect of hypoglycemic treatment between Asian and Caucasian type 2 diabetes patients. Methods: The MEDLINE®, EMBASE®, CENTRAL were searched and qualified studies were included. References were collected until Dec. 2015. All the studies were double blind, placebocontrolled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. Results: 250 studies compared a placebo with an active hypoglycemic agent either in Asian (n = 40) or in Caucasian (n = 210), placebo effect in HbA1c was comparable between Asian (0.09%, 95%CI, 0 to 0.18%) and Caucasian (−0.02%, 95%CI, −0.15 to 0.10%), placebo effect in FPG was comparable between Asian (0.21 mmol/L; 95% CI, 0.07–0.34 mmol/L) and Caucasian (0.1 mmol/L; 95% CI, −0.09 to 0.29 mmol/L), placebo effect in weight was also comparable between Asian (−0.22 kg; 95% CI, −0.48–0.03 kg) and Caucasian (−0.02 kg; 95% CI, −0.48–0.44 kg). 40 studies compared a placebo with an AGI either in Asian (n = 25) or in Caucasian (n = 17), placebo effect in HbA1c was comparable between Asian (−0.13, 95%CI, −0.31 to 0.04) and Caucasian (0.08, 95%CI, −0.11 to 0.27). 83 trials compared a placebo with a TZD either in Asian (n = 38) or in Caucasian (n = 46), placebo effect in HbA1c was superior in Asian (−0.33, 95%CI, −0.64 to −0.03) to that in Caucasian (0.12, 95%CI, −0.03 to 0.27). 57 trials compared a placebo with a DPP-IV inhibitors either in Asian (n = 20) or in Caucasian (n = 39), placebo effect in HbA1c was comparable between Asian (0.02, 95%CI, −0.19 to 0.23) and Caucasian (−0.13, 95%CI, −0.26 to 0.01). For SU treatment, metformin treatment as well as SGLT2 inhibitors treatment, no enough studies were found for the comparisons between Asian and Caucasian population. Conclusion: Results from this meta-analysis indicated that the placebo effect in hypoglycemic drugs was comparable between Asian and Caucasian type 2 diabetes patients. PJ-13 Safety and efficacy comparison of different insulin regimens in T2DM patients: A meta-analysis Xueying GAO1, Xiaoling CAI1, Wenjia YANG1, Linong JI1 *. 1 Peking University People’s Hospital, China To compare the safety and efficacy in T2DM patients treated with different insulin regimens, we searched the following databases: MEDLINE, EMBASE, CENTRAL. References were collected until Dec. 2015. The main search concepts were type 2 diabetes, NPH insulin, long acting insulin analogs, human regular insulin, rapid insulin analogs, premixed insulin, premixed insulin analogs, randomized controlled trials (RCTs), and clinical trials. Inclusion criteria were: (1) T2DM patients aged >18 years; (2) RCTs with at least 4 weeks of follow-up; (3) different insulin regimens were evaluated and compared. A total of 74 articles were included in this review. (1) NPH insulin versus long acting insulin analogs therapy (twenty-two studies): Treatment with long acting insulin analogs was associated with a significantly greater decrease in HbA1c and FPG level, a significantly lower increase in body weight, and a significantly lower risk of hypoglycemia. Treatment with NPH insulin was associated with a significantly lower insulin dosage. No statistically significant difference was found in terms of all-cause mortality between two groups. (2) Human regular insulin versus rapid insulin analogs therapy (nine studies): Treatment with rapid insulin analogs was associated
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with a significantly greater decrease in HbA1c. No statistically significant difference was found in FPG change, body weight change, insulin dosage, rate of hypoglycemia, and all-cause mortality between two groups. (3) Premixed insulin versus premixed insulin analogs therapy (six studies): Treatment with premixed insulin was associated with a significantly greater increase in body weight. No statistically significant difference was found in HbA1c change, FPG change, insulin dosage, rate of hypoglycemia, and all-cause mortality between two groups. (4) Premixed insulin versus basal insulin therapy (twenty studies): Treatment with premixed insulin was associated with a significantly greater decrease in HbA1c level, and a significantly greater increase in body weight. Treatment with basal insulin was associated with a significantly lower insulin dosage, and a significantly lower risk of hypoglycemia. No statistically significant difference was found in FPG change, and all-cause mortality between two groups. (5) Premixed insulin versus basal-bolus/bolus insulin therapy (twenty-one studies): Treatment with basal-bolus/ bolus insulin was associated with a significantly greater decrease in FPG change. No statistically significant difference was found HbA1c change, body weight change, insulin dosage, rate of hypoglycemia, and all-cause mortality between two groups. Results from this meta-analysis comprehensively evaluated the glucose control and the hypoglycemic rate as well as allcause mortality in different kinds of insulin treatment. PJ-14 Metformin as an anticancer agent in breast cancer therapy by regulating tumor associated macrophage polarization and function Chi-Fu CHIANG1 *, Yi-Jen HUNG2, Yi-Shing SHIEH3,4, Chien-Hsing LEE1,2. 1Graduate Institute of Medical Sciences, National Defense Medical Center, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 3School of Dentistry, National Defense Medical Center, 4Department of Oral Diagnosis and Pathology, Tri-Service General Hospital, Taipei, Taiwan Background: Accumulated evidence suggests that diabetic patients treated with metformin had a significantly lower risk of developing cancer or a lower cancer mortality. Recent evidence suggested that the phenotype of TAMs varies from M1 to M2 with the stage of tumor progression. However, it is not known if metformin is involved in TAMs phenotype switch to affect tumor malignant behaviors. Material and methods: We used the THP-1 macrophage cultured with breast cancer conditioned medium as tumor microenvironment model. Results: We found that metformin significantly switched from M2 to M1 phenotype in breast cancer conditioned medium, by reduced expression of CD206, down-regulation of M2 marker mRNA, and enhanced expression of CD16, up-regulation of M1 marker mRNA. But metformin not be direct influence THP-1 macrophage polarization. Moreover, we found that metformin can affect cytokines secretion in the breast cancer, by reduced expression of IL-4, IL-10, IL-13, and induced IFN-γ through AMPK-NF-κB signaling to regulate, and then affect macrophage polarization. Administration of CC, another inhibitor of AMPK, also blocked the switched from M2 to M1 phenotype. In tumor tissue, the percentage of M2-like macrophage was decreased and M1-like macrophage was increased in the metformin group. Conclusion: These findings suggest that metformin treatment can induce cytokines secretion and expression by AMPK-NF-κB pathway in breast cancer and then affect TAM polarization.
PJ-12 Comparisons of placebo effect of hypoglycemic drugs between Asian and Caucasian type 2 diabetes patients Xiaoling CAI1 *, Lingli ZHOU1, Wenjia YANG1, Xueyao HAN1, Linong JI1. 1Peking University People’s Hospital, China Aim: It was hypothesis that the placebo effect might be different between different ethnicity. The aim of this study is to compare the placebo effect of hypoglycemic treatment between Asian and Caucasian type 2 diabetes patients. Methods: The MEDLINE®, EMBASE®, CENTRAL were searched and qualified studies were included. References were collected until Dec. 2015. All the studies were double blind, placebocontrolled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. Results: 250 studies compared a placebo with an active hypoglycemic agent either in Asian (n = 40) or in Caucasian (n = 210), placebo effect in HbA1c was comparable between Asian (0.09%, 95%CI, 0 to 0.18%) and Caucasian (−0.02%, 95%CI, −0.15 to 0.10%), placebo effect in FPG was comparable between Asian (0.21 mmol/L; 95% CI, 0.07–0.34 mmol/L) and Caucasian (0.1 mmol/L; 95% CI, −0.09 to 0.29 mmol/L), placebo effect in weight was also comparable between Asian (−0.22 kg; 95% CI, −0.48–0.03 kg) and Caucasian (−0.02 kg; 95% CI, −0.48–0.44 kg). 40 studies compared a placebo with an AGI either in Asian (n = 25) or in Caucasian (n = 17), placebo effect in HbA1c was comparable between Asian (−0.13, 95%CI, −0.31 to 0.04) and Caucasian (0.08, 95%CI, −0.11 to 0.27). 83 trials compared a placebo with a TZD either in Asian (n = 38) or in Caucasian (n = 46), placebo effect in HbA1c was superior in Asian (−0.33, 95%CI, −0.64 to −0.03) to that in Caucasian (0.12, 95%CI, −0.03 to 0.27). 57 trials compared a placebo with a DPP-IV inhibitors either in Asian (n = 20) or in Caucasian (n = 39), placebo effect in HbA1c was comparable between Asian (0.02, 95%CI, −0.19 to 0.23) and Caucasian (−0.13, 95%CI, −0.26 to 0.01). For SU treatment, metformin treatment as well as SGLT2 inhibitors treatment, no enough studies were found for the comparisons between Asian and Caucasian population. Conclusion: Results from this meta-analysis indicated that the placebo effect in hypoglycemic drugs was comparable between Asian and Caucasian type 2 diabetes patients. PJ-13 Safety and efficacy comparison of different insulin regimens in T2DM patients: A meta-analysis Xueying GAO1, Xiaoling CAI1, Wenjia YANG1, Linong JI1 *. 1 Peking University People’s Hospital, China To compare the safety and efficacy in T2DM patients treated with different insulin regimens, we searched the following databases: MEDLINE, EMBASE, CENTRAL. References were collected until Dec. 2015. The main search concepts were type 2 diabetes, NPH insulin, long acting insulin analogs, human regular insulin, rapid insulin analogs, premixed insulin, premixed insulin analogs, randomized controlled trials (RCTs), and clinical trials. Inclusion criteria were: (1) T2DM patients aged >18 years; (2) RCTs with at least 4 weeks of follow-up; (3) different insulin regimens were evaluated and compared. A total of 74 articles were included in this review. (1) NPH insulin versus long acting insulin analogs therapy (twenty-two studies): Treatment with long acting insulin analogs was associated with a significantly greater decrease in HbA1c and FPG level, a significantly lower increase in body weight, and a significantly lower risk of hypoglycemia. Treatment with NPH insulin was associated with a significantly lower insulin dosage. No statistically significant difference was found in terms of all-cause mortality between two groups. (2) Human regular insulin versus rapid insulin analogs therapy (nine studies): Treatment with rapid insulin analogs was associated
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with a significantly greater decrease in HbA1c. No statistically significant difference was found in FPG change, body weight change, insulin dosage, rate of hypoglycemia, and all-cause mortality between two groups. (3) Premixed insulin versus premixed insulin analogs therapy (six studies): Treatment with premixed insulin was associated with a significantly greater increase in body weight. No statistically significant difference was found in HbA1c change, FPG change, insulin dosage, rate of hypoglycemia, and all-cause mortality between two groups. (4) Premixed insulin versus basal insulin therapy (twenty studies): Treatment with premixed insulin was associated with a significantly greater decrease in HbA1c level, and a significantly greater increase in body weight. Treatment with basal insulin was associated with a significantly lower insulin dosage, and a significantly lower risk of hypoglycemia. No statistically significant difference was found in FPG change, and all-cause mortality between two groups. (5) Premixed insulin versus basal-bolus/bolus insulin therapy (twenty-one studies): Treatment with basal-bolus/ bolus insulin was associated with a significantly greater decrease in FPG change. No statistically significant difference was found HbA1c change, body weight change, insulin dosage, rate of hypoglycemia, and all-cause mortality between two groups. Results from this meta-analysis comprehensively evaluated the glucose control and the hypoglycemic rate as well as allcause mortality in different kinds of insulin treatment. PJ-14 Metformin as an anticancer agent in breast cancer therapy by regulating tumor associated macrophage polarization and function Chi-Fu CHIANG1 *, Yi-Jen HUNG2, Yi-Shing SHIEH3,4, Chien-Hsing LEE1,2. 1Graduate Institute of Medical Sciences, National Defense Medical Center, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 3School of Dentistry, National Defense Medical Center, 4Department of Oral Diagnosis and Pathology, Tri-Service General Hospital, Taipei, Taiwan Background: Accumulated evidence suggests that diabetic patients treated with metformin had a significantly lower risk of developing cancer or a lower cancer mortality. Recent evidence suggested that the phenotype of TAMs varies from M1 to M2 with the stage of tumor progression. However, it is not known if metformin is involved in TAMs phenotype switch to affect tumor malignant behaviors. Material and methods: We used the THP-1 macrophage cultured with breast cancer conditioned medium as tumor microenvironment model. Results: We found that metformin significantly switched from M2 to M1 phenotype in breast cancer conditioned medium, by reduced expression of CD206, down-regulation of M2 marker mRNA, and enhanced expression of CD16, up-regulation of M1 marker mRNA. But metformin not be direct influence THP-1 macrophage polarization. Moreover, we found that metformin can affect cytokines secretion in the breast cancer, by reduced expression of IL-4, IL-10, IL-13, and induced IFN-γ through AMPK-NF-κB signaling to regulate, and then affect macrophage polarization. Administration of CC, another inhibitor of AMPK, also blocked the switched from M2 to M1 phenotype. In tumor tissue, the percentage of M2-like macrophage was decreased and M1-like macrophage was increased in the metformin group. Conclusion: These findings suggest that metformin treatment can induce cytokines secretion and expression by AMPK-NF-κB pathway in breast cancer and then affect TAM polarization.