Efficacy and safety of once-weekly exenatide after switching from twice-daily exenatide in patients with type 2 diabetes.

AIMS/INTRODUCTION: To evaluate the efficacy and safety of once-weekly (q.w.) extended-release exenatide after switching from twice-daily (b.i.d.) exenatide in patients with type 2 diabetes. MATERIALS AND METHODS: This was an investigator-initiated, prospective, single-arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end-point was change in HbA1c at week 24 to test the glucose-lowering effect of exenatide q.w. versus exenatide b.i.d. RESULTS: A total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval -0.4 to -0.03%, P < 0.005 for non-inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). ß-Cell function assessed by homeostasis model assessment of ß-cell function and C-peptide index was significantly improved at week 24. The incidence of self-reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug. CONCLUSIONS: Switching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in ß-cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.

Assessment of energy expenditure using doubly labeled water, physical activity by accelerometer and reported dietary intake in Japanese men with type 2 diabetes: A preliminary study.

The aim of the present study was to determine the total energy expenditure, physical activity and dietary intake of men with type 2 diabetes mellitus and control participants without type 2 diabetes mellitus who were matched for age and body mass index. The participants in the present study were 12 well-controlled type 2 diabetes mellitus patients and 10 controls, aged 40-75 years, with a body mass index <30 kg/m2 . Total energy expenditure under free-living conditions was assessed using the doubly labeled water method, and physical activity was measured using a triaxial accelerometer. Dietary intake was assessed using a self-recorded food intake diary during the measurement period. Participants were instructed to record their dietary intake over 3 days, including 2 weekdays. Total energy expenditure was not significantly different between the groups (P = 0.153), nor were energy (P = 0.969) or macronutrient intakes. In conclusion, when age and body mass index are matched, total energy expenditure and self-reported energy intake are not significantly different between type 2 diabetes mellitus patients and healthy controls.

Efficacy of ezetimibe is associated with gender and baseline lipid levels in patients with type 2 diabetes.

AIM: The combination of ezetimibe and a statin provides greater LDL-C reduction by inhibiting both intestinal cholesterol absorption and endogenous production of cholesterol. The present study was designed to examine the influence of ageing, gender, BMI, levels of LDL-C, and HbA1c on the response to ezetimibe add-on therapy. METHODS: Patients who had been taking a statin for >3 months at the usual dose and whose LDL-C was >120 mg/dL were eligible for this study. Patients were assigned to receive add-on ezetimibe at 10 mg once daily for 12 weeks. RESULTS: Adding ezetimibe to basal statin therapy resulted in a further 15.0% reduction of TC, 20.5% reduction of LDL-C, and 19.7% reduction of non-HDL-C. The change in TC was significantly greater in males than in females. The change in TG was significantly greater in patients with a baseline TG level ≥150 mg/dL. Multivariate regression analysis showed that male sex and LDL-C ≥140 mg/dL were independent predictors of TC reduction after adjustment for age, BMI, and HbA1c. A baseline TG ≥150 mg/dL was also an independent predictor of TG reduction. CONCLUSION: Addition of ezetimibe to ongoing statin therapy was effective in patients with type 2 diabetes. Male sex and baseline LDL-C levels are independent predictors of marked TC reduction by ezetimibe treatment.

Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to suppression of N(ɛ)-carboxymethyl lysine.

OBJECTIVE: We investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes. METHODS: A total of 38 type 2 diabetic patients (22 men and 16 women; mean ± S.E.M. age 63.3 ± 1.0 years; duration of diabetes 9.6 ± 0.8 years) with diabetic neuropathy were newly administered 150 mg/day epalrestat (EP group). Motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), and minimum F-wave latency were evaluated before administration of epalrestat and after 1 and 2 years. Serum N(ɛ)-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-1 as a parameter of angiopathy were measured before administration and after 1 year. We compared the results with those of 36 duration of diabetes-matched type 2 diabetic patients (mean ± S.E.M. duration of diabetes 8.2 ± 0.7 years) as control (C group). RESULTS: The EP group showed significant suppression of deterioration of MCV (P<.01) and minimum F-wave latency (P<.01) in the tibial nerve and SCV (P<.05) in the sural nerve compared to those in the C group after 2 years. There was a significant difference in change in CML level between groups (-0.18 ± 0.13 mU/ml in the EP group vs. +0.22 ± 0.09 mU/ml in the C group, P<.05) after 1 year. CONCLUSIONS: Epalrestat suppressed the deterioration of diabetic peripheral neuropathy, especially in the lower extremity. Its effects might be mediated by improvement of the polyol pathway and suppression of production of AGEs.

Insulin-like growth factor-1 (IGF-1)-derived peptide protects against diabetes in NOD mice.

Spontaneous diabetes in non-obese diabetic (NOD) mice results from beta-cell destruction by autoreactive T lymphocytes. Here, we report the significance of insulin-like growth factor-1 (IGF-1) peptide as a tool for the prevention of type 1 diabetes. Female NOD mice were immunized with a subcutaneous injection of IGF-1, glutamic acid decarboxylase (GAD), insulin or IGF-1-derived peptides (residues 8-23, 24-41 or 50-70) in incomplete Freund's adjuvant (IFA) or with IFA only as the control group at 4 weeks of age, and observed up to 36-37 weeks of age. Diabetes onset was significantly suppressed and delayed in the IGF-1 group as compared to the GAD, insulin and control groups (p<0.05), and it was significantly suppressed and delayed in the (50-70)IGF-1 group as compared to the (8-23)IGF-1 and control groups (p<0.02). Although the degree of insulitis in all treated mice was not significantly different, a significant number of IL-4-producing cells in response to IGF-1 peptides were detected in (50-70)IGF-1-treated mice in intracellular cytokine assay. In conclusion, IGF-1 peptide 50-70 immunizations of NOD mice suppressed and delayed diabetes onset, probably through amplification of the Th2-type response. It was suggested that IGF-1 peptide 50-70 immunization can be used as a tool for prevention of type 1 diabetes.