Efficacy of mitiglinide and sitagliptin,alone or in combination,on postprandial excursion and glycemic variability assessed by continuous glucose monitoring: a post hoc analysis with single-day treatment

Objective: To compare the efficacy of mitiglinide and sitagliptin, alone or in combination, on postprandial excursion and glycemic variability assessed by continuous glucose monitoring (CGM) in a single-day treatment setting.

Methods: This was a post hoc analysis of a randomized crossover study comparing the efficacy of sitagliptin, mitiglinide and the combination of these two drugs. Twenty-four hour CGM was performed before and after a single-day treatment with each drug alone or in combination.

Results: Mean glucose levels were decreased in all groups. The average of three postprandial glucose excursions AUC (average of all three 4-h postprandial periods throughout the day) (AUCpp-average) decreased in the mitiglinide and combination treatment groups, but not in the sitagliptin group. The lowering effect on AUCpp-average was greater in patients given mitiglinide (–47 mg/dl, p < 0.001) or combination treatment (–66 mg/dl, p < 0.001) compared with sitagliptin alone (–18 mg/dl). The reduction in mean amplitude of glycemic excursion was greater with mitiglinide (–29.3 mg/dl, p < 0.001) and combination treatment (–28.3 mg/dl, p < 0.01) than with sitagliptin alone (–8.9 mg/dl).

Conclusions: Mitiglinide or combination treatment resulted in lower glycemic variability and postprandial glucose excursion than sitagliptin alone; however, the results of this single-day pharmacodynamics study cannot be generalized to a clinical setting.     

Effects of sitagliptin or mitiglinide as an add-on to acarbose on daily blood glucose fluctuations measured by 72 h subcutaneous continuous glucose monitoring in Japanese patients with type 2 diabetes: a prospective randomized study

Objective: Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life.

Methods: Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 – 7 days in week 3 of each treatment period.

Results: The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period.

Conclusion: Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.     

Glycemic/metabolic responses to identical meal tolerance tests at breakfast,lunch and dinner in Japanese patients with type 2 diabetes mellitus treated with a dipeptidyl peptidase-4 inhibitor and the effects of adding a mitiglinide/voglibose fixed-dose combination

Background: The effects of the mitiglinide/voglibose fixed-dose combination on postprandial glycemic/metabolic responses in patients with type 2 diabetes mellitus (T2DM) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors are unknown.

Methods: Twelve T2DM patients treated with a DPP-4 inhibitor underwent identical meal tolerance tests (MTTs) at breakfast, lunch and dinner, before and 2 – 3 weeks after treatment with a fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg (combination). Patients were randomized in a cross-over fashion to administer the combination either three-times-daily before each meal or twice-daily before breakfast and dinner. Glycemic/metabolic responses were evaluated at 0, 30, 60 and 120 min in each MTT.

Results: Three-times-daily administration of the combination significantly suppressed postprandial hyperglycemia after each meal, particularly after lunch and dinner. Active glucagon-like peptide-1 levels increased significantly after each meal, as did early-phase insulin secretion without excessive insulin secretion. Postprandial hyperglycemia after lunch was significantly greater after twice-daily than three-times-daily administration, but there were no clinically relevant differences in other metabolic responses.

Conclusion: This study revealed that adding the mitiglinide/voglibose combination to a DPP-4 inhibitor elicited additive improvements in postprandial glycemic/metabolic responses assessed using MTTs at breakfast, lunch and dinner with identical meal compositions.     

Mitiglinide/voglibose fixed-dose combination improves postprandial glycemic excursions in Japanese patients with type 2 diabetes mellitus

Objective: We examined the effects of a fixed-dose combination of 10 mg mitiglinide and 0.2 mg voglibose on postprandial glycemic excursions in Japanese type 2 diabetes mellitus (T2DM) patients.

Research design and methods: After a 2-week baseline period, 11 T2DM patients were treated with mitiglinide alone for 2 weeks and with the mitiglinide/voglibose combination for 6 weeks.

Main outcome measures: Self-monitoring of blood glucose (SMBG) at home before and after unified meals, metabolic parameters during meal tolerance tests, and overall glycemic control parameters.

Results: Postprandial glycemic excursions after all three meals, as assessed by SMBG, were significantly lower in the combination period than in the baseline period, and after lunch and dinner in the combination period than in the mitiglinide period. The meal tolerance test confirmed that the magnitude of postprandial hyperglycemia was significantly lower, with significantly greater early-phase serum insulin secretion and sustained GLP-1 production, in the combination period compared with the baseline period. Overall glycemic control parameters also improved significantly in the combination period compared with the baseline period. These profiles suggest the combination is superior to mitiglinide alone, and may spare insulin secretion.

Conclusion: The mitiglinide/voglibose combination significantly reduced postprandial glycemic excursions in Japanese T2DM patients. This trial was registered with the University Hospital Medical Information Network clinical trials database (no. UMIN000007202).     

The glycemic/metabolic responses to meal tolerance tests at breakfast,lunch and dinner,and effects of the mitiglinide/voglibose fixed-dose combination on postprandial profiles in Japanese patients with type 2 diabetes mellitus

Background: Meal tolerance tests (MTTs) are usually conducted at breakfast after overnight fasting in type 2 diabetes mellitus (T2DM) patients, but differences in postprandial glycemic responses between meals have been reported.

Objective: We conducted MTTs at breakfast, lunch, and dinner to examine the effects of a fixed combination of 10 mg mitiglinide/0.2 mg voglibose (the combination) on glycemic/metabolic responses to meals during the day in T2DM patients. MTTs with unified meals were conducted in 11 T2DM patients before and after 4 weeks of treatment with the combination administered thrice daily before meals. Glycemic/metabolic profiles measured before and at 30, 60, and 120 min after each meal were compared between each meal and between the baseline and treatment periods.

Results and conclusion: The combination significantly reduced postprandial hyperglycemia after each meal. Postprandial AUC_{0 – 120 min} for insulin significantly decreased after lunch and dinner compared with after breakfast, while insulin levels significantly increased at only 30 min after breakfast and dinner. The combination also significantly increased postprandial C-peptide and active glucagon-like peptide-1 levels, and reduced free fatty acid and triglyceride levels, but did not significantly affect glucagon levels compared with baseline, confirming that treatment with the combination improves postprandial responses in Japanese T2DM patients.     

Tighter control of postprandial hyperglycemia with mitiglinide/voglibose fixed-dose combination in Japanese patients with type 2 diabetes mellitus

Objective: The objective of this study was to compare the effects of mitiglinide, voglibose and its combination on metabolic responses after a test meal in Japanese patients with type 2 diabetes mellitus (T2DM).

Research design and methods: This randomized crossover study consisted of four periods between August and November 2011. In the first period, all patients (n = 12) received water alone (control period). In the next three periods, the patients received 10 mg mitiglinide, 0.2 mg voglibose or a combination in a random order.

Main outcome measures: Postprandial metabolite/hormone levels were then measured.

Results: Plasma glucose and serum insulin reached peak levels by 60 – 90 and 90 min, respectively, after the test meal in the control group. The combination reduced postprandial glucose levels compared with mitiglinide or voglibose alone, particularly at 30 – 90 min, which significantly exceeded the effects of mitiglinide (p < 0.05). Mitiglinide and the combination restored early insulin response, whereas the combination provided an insulin-sparing effect compared with mitiglinide alone. The combination improved postprandial lipid profiles, combining the effects of both drugs.

Conclusion: This study revealed marked differences in the postprandial metabolic effects of mitiglinide, voglibose and its combination in patients with T2DM. The combination therapy should enable tighter control of postprandial hyperglycemia compared with the individual drugs.     

Effects of exenatide versus sitagliptin on postprandial glucose,insulin and glucagon secretion,gastric emptying,and caloric intake: a randomized,cross-over study

ABSTRACT

Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients.

Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33?±?5?kg/m²; HbA_1c: 8.5?±?1.2%; 2-h PPG: 245?±?65?mg/dL. Patients received exenatide (5?µg BID for 1 week, then 10?µg BID for 1 week) or sitagliptin (100?mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581).

Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133?±?6?mg/dL versus 208?±?6?mg/dL, p?<?0.0001 (evaluable, N?=?61). Switching from exenatide to sitagliptin increased 2-h PPG by +73?±?11?mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by ?76?±?10?mg/dL. Postprandial glucose parameters (AUC, C_ave, C_max) were lower with exenatide than sitagliptin (p?<?0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (?15?±?4?mg/dL vs. ?19?±?4?mg/dL, p?=?0.3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50?±?0.26, p?=?0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88?±?0.03, p?=?0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90?±?0.04, p?=?0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56?±?0.05, p?<?0.0001). Exenatide reduced total caloric intake compared to sitagliptin (?134?±?97?kcal vs. +130?±?97?kcal, p?=?0.0227, N?=?25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature.

Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.     

Comparison of the hypoglycemic effect of sitagliptin versus the combination of mitiglinide and voglibose in drug-naïve Japanese patients with type 2 diabetes

Objective: The postprandial glucose (PPG) level is reduced by α-GIs, glinides and DPP4Is through different pharmacological actions. The aim of this study was to compare the effect of sitagliptin (S) versus that of the combination of mitiglinide and voglibose (M+V) on markers of glycemic control.

Research design and methods: A randomized cross-over trial was performed in 20 patients with drug-naïve type 2 diabetes. The patients were randomized to receive S (50 mg/day) or M+V (1 tablet 3 times daily). Treatment was continued for 8 weeks, after which they were switched to the other regimen and treated for another 8 weeks. At baseline, after the first regimen, and after the second regimen, a meal test was performed.

Main outcome measures: The markers of glycemic control were examined.

Results: Reduction of glucose excursion was significantly greater with M+V than with S. HbA_1c did not change with either regimen. However, 1,5-anhydroglucitol showed a significant increase from baseline with both regimens (7.9 ± 4.3 μg/ml at baseline vs. 10.6 ± 5.5 with S, p < 0.05 and 15.1 ± 6.2 with M+V, p < 0.01). Compared with baseline, glycoalbumin was significantly reduced by M+V, but not S (19.6 ± 2.9% at baseline vs. 17.3 ± 3.8% with M+V, p < 0.05).

Conclusion: M+V achieved better control of PPG excursion than S.     

Antidiabetic,antihyperlipidaemic, and antioxidant activity of Syzygium densiflorum fruits in streptozotocin and nicotinamide-induced diabetic rats

Context Syzygium densiflorum Wall. ex Wight & Arn (Myrtaceae) has been traditionally used by local tribes of the Nilgiris, Tamil Nadu, India, for the treatment of diabetes, however, no definitive experimental studies are available.

Objective This study investigates the antidiabetic, antihyperlipidaemic and antioxidant activities of ethanol extract of S. densiflorum (EFSD) fruits in streptozotocin (STZ) and nicotinamide (NA)-induced diabetic rats.

Materials and methods Acute oral toxicity and oral glucose tolerance were assessed in normal rats. The antidiabetic, antihyperlipidaemic and antioxidant activities were investigated in STZ???NA-induced diabetic rats. Diabetic rats were orally administered with glibenclamide (10?mg/kg b.wt), EFSD (200, 400 and 800?mg/kg b.wt) for 28 d. Further, changes in the blood glucose level (BGL), biochemical parameters, antioxidants were observed and histology of pancreas was performed.

Results No toxicity and lethality were observed. Results of the following parameters are represented by treated versus disease control (STZ?+?NA) groups. BGL (161.33?±?22.8 versus 476.17?±?56.58?mg/dl), glycosylated haemoglobin (5.285?±?0.19 versus 8.05?±?0.55%), urea (40.32?±?1.96 versus 75.37?±?2.91?mg/dl), uric acid (1.2?±?0.07 versus 2.16?±?0.05?mg/dl), total cholesterol (89.3?±?5.14 versus 139.7?±?5.95?mg/dl) and triglycerides (79.65?±?2.52 versus 108.9?±?3.61?mg/dl) were significantly decreased, whereas haemoglobin (11.75?±?0.73 versus 7.95?±?0.42?g/dl), high‐density lipoprotein cholesterol (14.2?±?1.11 versus 6.97?±?0.84?mg/dl), total protein (45%) and liver glycogen (87%) were significantly increased in EFSD-treated diabetic group. Significant changes were observed in the enzymatic and non-enzymatic antioxidants in EFSD-treated groups (p?<?0.001). Histopathological examination showed the regeneration of β-cells in Islets of Langerhans.

Conclusion This study confirms the antidiabetic, antihyperlipidaemic and antioxidant activities of S. densiflorum fruits.     

Comparison of glycemic variability in Japanese patients with type 1 diabetes receiving insulin degludec versus insulin detemir using continuous glucose monitoring: a randomized,cross-over,pilot study

Objective: To use continuous glucose monitoring (CGM) to compare glycemic variability in patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) versus insulin detemir (IDet).

Methods: Ten patients with T1D were randomly assigned to receive once-daily IDeg, followed by twice-daily IDet, or vice versa. Glucose variability was evaluated by CGM after >4 weeks of the first insulin and again after crossover to the second insulin.

Results: The total daily insulin dose (U/kg/day) and the total daily basal insulin dose (U/kg/day) were significantly lower during treatment with IDeg than with IDet [median (interquartile range): 0.55 (0.54–0.73) vs. 0.64 (0.54–0.83); P = 0.028, 0.24 (0.19–0.36) vs. 0.30 (0.19–0.39); P = 0.027]. The 24-hour mean glucose levels were not significantly different. However, their standard deviation (SD) was significantly smaller during treatments with IDeg than those with IDet [59.5 (39.5–71.0) vs. 72.8 (61.8–92.8); P = 0.008]. Their mean fasting glucose levels and the mean postprandial peak levels after breakfast and after dinner were significantly lower with IDeg.

Conclusions: A CGM-based comparison demonstrated that once-daily IDeg showed fewer glycemic fluctuations than twice-daily IDet. IDeg appears to stabilize blood glucose levels better during both daytime and nighttime (particularly, before and after breakfast) with a lower insulin dosage.     

Combination therapy with mitiglinide and voglibose improves glycemic control in type 2 diabetic patients on hemodialysis

Objective: Mitiglinide, a rapid- and short-acting insulinotropic sulfonylurea receptor ligand, exhibits hypoglycemic action unlike other sulfonylureas. The efficacy of the combination of mitiglinide and α-glucosidase inhibitors for diabetic patients on hemodialysis (HD) has not been prospectively evaluated; therefore, we evaluated the efficacy and safety of mitiglinide in these patients.

Research design and methods: We performed an open-label randomized study with 36 type 2 diabetics with poor glycemic control on HD and receiving daily doses of voglibose (0.9 mg). The patients were randomly assigned to two groups: a combination-therapy group (mitiglinide group), mitiglinide initial dose 7.5 – 15 mg titrated to 30 mg daily and constant daily dose 0.9 mg of voglibose, and a monotherapy group (control group), constant daily dose 0.9 mg of voglibose alone. The efficacy of the treatment was determined by monitoring plasma glucose, hemoglobin A1c (Hb_A1c), and glycated albumin (GA) levels and using homeostasis model assessment of insulin resistance (HOMA-IR). Safety and tolerance were determined by monitoring clinical and laboratory parameters.

Results: The final dose of mitiglinide was 22.9 ± 8.9 (mean ± s.d.) mg (0.41 mg/kg) daily. Mitiglinide reduced fasting plasma glucose and GA levels after 4 weeks and Hb_A1c levels after 8 weeks. Triglyceride levels and HOMA-IR values also decreased significantly after mitiglinide treatment. No significant changes in blood pressure levels or serious adverse effects such as hypoglycemia or liver impairment were observed.

Conclusions: This study suggests a combination therapy of mitiglinide and voglibose may have potential for the treatment of diabetics on HD. Due to the small sample size used, further studies should be performed, particularly to assess the safety of mitiglinide treatment.     

Comparison of efficacy and safety of taking miglitol dissolved in water during a meal and taking a miglitol tablet just before a meal in patients with type 2 diabetes

Objective: We compared the efficacy and safety of taking miglitol dissolved in water during a meal and taking a miglitol tablet just before a meal. Primary efficacy parameter is the area under the curve (AUC) for postprandial plasma glucose.

Methods: Miglitol was administered according to three different intake schedules in each subject: intake schedule A, no miglitol; intake schedule B, administration of miglitol (50 mg) just before breakfast; intake schedule C, dissolving miglitol (50 mg) in water and taking it just before (1/3), during (1/3), and just after breakfast (1/3). Blood samples were collected at 0, 30, 60, 120, and 180 min after breakfast.

Results: The AUCs for plasma glucose, insulin, and total glucose-dependent insulinotropic polypeptide (GIP) were significantly lower for intake schedules B and C, compared with those for intake schedule A. The AUC for total glucagon like peptide-1(GLP-1) was higher for intake schedule C than for intake schedule A. The coefficient of variation (CV) of plasma glucose was significantly lower for intake schedule C than for intake schedules A and B.

Conclusion: Taking miglitol dissolved in water was equivalent to taking a miglitol tablet. The CV of plasma glucose was significantly lower for the dissolved-dose regimen.     

The rationale for paired pre- and postprandial self-monitoring of blood glucose: the role of glycemic variability in micro- and macrovascular risk

ABSTRACT

Background: Decisions regarding diabetes management traditionally have been driven by the results of fasting plasma glucose measurement or measurement of glycosylated hemoglobin (A1C), yet glycemic control remains far from optimal in many individuals with diabetes. Mounting evidence implicates glycemic variability, manifested predominantly as postprandial glycemic spikes, as a key factor in the development of macrovascular complications. Recent studies suggest that newer therapies specifically targeting postprandial hyperglycemia can significantly reduce postprandial glucose levels and improve overall glycemic control.

Methods: A Medline search was performed using the term ‘postchallenge’ or ‘postprandial’, together with glucose or diabetes. After excluding review articles and case studies, we reviewed primary articles, meta-analyses, and references therein and selected those that best addressed this topic. Selection bias may be considered a potential limitation of this approach.

Findings: Although not conclusively demonstrated by prospective studies, a wealth of evidence suggests that postprandial hyperglycemia should not be ignored as an important target for preventing complications of diabetes.

Conclusions: Improved detection and management of postprandial hyperglycemia and glycemic variability is necessary to optimize glycemic control. Meal-based self-monitoring of blood glucose (SMBG) has been shown to improve glycemic control as part of a comprehensive management strategy by helping patients understand the effects of food choices, physical activity, and medications on blood glucose concentrations. SMBG can also help healthcare professionals recognize postprandial hyperglycemia, guide therapeutic adjustments and receive more timely feedback regarding medication changes. The arrival of new therapies that specifically target postprandial hyperglycemia offer healthcare professionals the opportunity to optimally manage diabetes.     

Effects of a Fixed Mixture of 25% Insulin Lispro and 75% NPL on Plasma Glucose during and after Moderate Physical Exercise in Patients with Type 2 Diabetes

Summary

Objective: To compare the plasma glucose (PG) response with a fixed mixture of 25% insulin lispro and 75% NPL (Mix25), prior to a meal and 3?h before exercise, to human insulin 30/70 (30/70) in patients with type 2 diabetes.

Research design and methods: Thirty-seven patients were treated in a randomized, open-label, 8-week, two-period crossover study. Mix25 was injected 5?min before breakfast and dinner throughout the study, as was 30/70 on inpatient test days and on outpatient dose titration days. Following the 4-week outpatient phase, patients were hospitalized, and exercised at a heart rate of 120 beats/min on a cycle ergometer two times for 30?min, separated by 30?min rest, starting 3?h after a 339 kcal breakfast.

Results: The 2-h postprandial PG was significantly lower with Mix25 ((mean?±?SEM) 10.5?±?0.4 mmol/lvs 11.6?±?0.4 mmol/l; p?=?0.016). Maximum decrease in PG from onset of exercise to end of exercise was significantly less with Mix25 (-3.6?±?0.29 mmol/l vs -4.7?±?0.31 mmol/l; p?=?0.001). The maximum decrease in PG over 6?h, after exercise onset, was significantly less with Mix25 (-4.3?±?0.4 mmol/l vs -5.9?±?0.4 mmol/l; p?<?0.001). The frequency of hypoglycemia (blood glucose (BG) < 3 mmol/l or symptoms) during the inpatient test was not different between treatments. During the outpatient phase, the frequency of patient-recorded hypoglycemia was significantly lower with Mix25 (0.7?±?0.2 episodes/30d vs 1.2?±?0.3 episodes/30 d; p?=?0.042).

Conclusions: Mix25 resulted in better postprandial PG control without an increase in exercise-induced hypoglycemia. The smaller decrease in PG during the postprandial phase after exercise may suggest a lower risk of exercise-induced hypoglycemia with Mix25 than with human insulin 30/70, especially for patients in tight glycemic control.     

Antifatigue properties of tanshinone IIA in mice subjected to the forced swimming test

Context: Tanshinone IIA (Tan IIA) is a constituent of Danshen Salvia miltiorrhiza Bunge (Lamiaceae); however, its antifatigue activity remains unclear.

Objective: To study the antifatigue properties of Tan IIA and its underlying mechanisms.

Materials and methods: In program I, three mouse groups were separately subjected to three gavages with 0, 1 and 6?mg/kg Tan IIA and forced swimming test (FST) weekly for 8 weeks; in program II, one gavage with 0, 2 and 10?mg/kg Tan IIA was administered plus FST weekly for 4 weeks. Serum glucose, lactate, superoxide dismutase (SOD), malondialdehyde (MDA) and blood urea nitrogen (BUN) were determined after final FST.

Results: Tan IIA significantly prolonged swimming durations in program I but not in program II. Swimming times were 3208?±?1054 and 2443?±?1054?s for the 1 and 6?mg/kg treatments and 856?±?292?s for the vehicle control. The two doses significantly reduced serum glucose levels (40.3?±?8.5 and 60.0 1?±?11.8?mg/kg) and lactate levels (61.3?±?27.5 and 68.8?±?8.5?mg/kg) in treated mice compared with those in control mice (137.5?±?38.6?mg/kg and 122.7?±?18.2?mg/kg, respectively). However, no significant differences were observed regarding SOD, MDA or BUN levels.

Discussion and conclusions: Tan IIA has antifatigue activity and is associated with reductions in serum glucose and lactate levels. Further studies should assess muscle hypertrophy and efficient aerobic glycolysis caused by Tan IIA. Tan IIA has potential as a pharmacological agent for fatigue resistance.     

Efficacy and safety of canagliflozin monotherapy in Japanese patients with type 2 diabetes inadequately controlled with diet and exercise: a 24-week,randomized, double-blind,placebo-controlled,Phase III study

Objective: To examine the efficacy and safety of canagliflozin monotherapy, a sodium/glucose co-transporter 2 inhibitor, in Japanese type 2 diabetes patients.

Methods: In this double-blind, multi-centre Phase III study, patients aged ≥ 20 years with hemoglobin A1c (HbA1c) 7.0 – 10.0% on diet/exercise therapy alone received placebo or canagliflozin (100 or 200 mg) once daily for 24 weeks. The main outcome measure was the change in HbA1c from baseline to Week 24.

Results: The changes in HbA1c (?0.74 and ?0.76 vs + 0.29%), fasting plasma glucose (1 mg/dl = 0.0555 mmol/l; ?31.6 and ?31.9 vs + 3.7 mg/dl), 2-h plasma glucose after 75-g glucose load (?84.9 and ?79.0 vs ?0.5 mg/dl), body weight (percent change: ?3.76 and ?4.02 vs ?0.76%) and systolic blood pressure (?7.88 and ?6.24 vs ?2.72 mmHg) were significantly greater with 100 and 200 mg canagliflozin than with placebo (all, p < 0.05). Genital infections in females (6.5, 6.3 and 0%) and asymptomatic hypoglycemia (4.4, 5.6 and 2.2%), but not symptomatic hypoglycemia (2.2, 1.1 and 1.1%), were more frequent in the 100- and 200-mg groups than in the placebo group.

Conclusion: Canagliflozin significantly improved glycemic control and was well tolerated.     

The Effects of the Addition of Micronised Fenofibrate on Uric Acid Metabolism in Patients Receiving Indapamide

Summary

Objective: Hyperuricaemia is associated with indapamide administration. In contrast, micronised fenofibrate can significantly decrease serum uric acid levels. However, there are no data on the effect of combination therapy of indapamide with micronised fenofibrate on uric acid metabolism.

Methods: We studied 20 non-diabetic hypertensive patients with mixed dyslipidaemia in whom serum metabolic parameters, including uric acid levels in serum and urine, were measured before and after eight weeks of indapamide administration (2.5?mg once daily). This study was continued for a further eight weeks, when the indapamide was combined with micronised fenofibrate (200?mg once daily).

Results: Indapamide significantly decreased mean systolic and diastolic blood pressure (BP) from 153±9/97±8mmHgto 138 ± 8/93 ± 4mmHg (p < 0.05 for both comparisons). A significant increase in serumuric acid levels occurred after indapamide administration [from a mean value of5.6± 1.3mg/dl (0.33 ± 0.07 mmol/l) to 6.4 ± 1.1?mg/dl (0.38 ± 0.06mmol/l), p< 0.01]. This effect was associated with a decrease in the fractional excretion of uric acid (from a mean value of 9.5 ± 5% to 7 ± 5.5%, p < 0.05). The addition of micronised fenofibrate significantly decreased plasma fibrinogen levels as well as total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B (ApoB) and triglycerides, and increased high-density lipoprotein cholesterol and ApoA1 levels. Fenofibrate administration was followed by a significant decrease in serum uric acid levels to 4.7± 1.2?mg/dl (0.28 ± 0.07 mmol/l), p < 0.01, owing to a substantial increase in fractionalurate excretion to 11 ± 3%, p < 0.01.

Conclusion: The addition of micronised fenofibrate can correct the hyperuricaemic effect of indapamide administration.     

The dipeptidyl peptidase-4 inhibitor alogliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis

Objectives: The potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin improves glycemic control in patients with type 2 diabetes through incretin hormone-mediated increases in both α- and β-cell responsiveness to glucose. In this study, the efficacy and safety of alogliptin in type 2 diabetic patients undergoing hemodialysis (HD) were evaluated.

Methods: A prospective, open-label study of 30 patients (male/female: 24/6; mean age: 69.7 ± 1.7 years) with type 2 diabetes who were undergoing HD without insulin injection therapy was conducted. Patients were administered 6.25 mg/day alogliptin and efficacy and safety were determined by monitoring clinical and laboratory parameters during the 48-week study period.

Results: After 48 weeks, alogliptin had decreased postprandial plasma glucose levels from 212 ± 8 mg/dL baseline to 156 ± 7 mg/dL, hemoglobin A1c levels from 7.1 ± 0.2% baseline to 6.3 ± 0.2% and glycated albumin (GA) levels from 25.6 ± 0.6% baseline to 20.7 ± 0.4% (all p < 0.0001). Alogliptin efficacy did not differ according to median age or body mass index, but the GA reduction was significantly greater in the antidiabetic agents-naïve group. The magnitude of GA reduction was baseline GA-dependent, being greater at higher baseline GA levels. No serious adverse effects, such as hypoglycemia or liver impairment, were observed in any patient.

Conclusion: Alogliptin as monotherapy or in combination with other oral antidiabetic agents improved glycemic control and was generally well tolerated in patients with HD over a 48-week period.     

Steroid-induced diabetes mellitus and related risk factors in patients with neurologic diseases

STUDY OBJECTIVE: To determine the frequency of steroid-induced diabetes mellitus (SDM) and the related risk factors in patients with neurologic diseases who receive high doses of steroids. DESIGN: Retrospective chart review. SETTING: Neurology ward of a university-affiliated hospital. PATIENTS: Twenty-five patients with neurologic diseases who received prednisolone 30-60 mg/day orally after breakfast for more than 2 weeks. MEASUREMENTS AND MAIN RESULTS: Plasma glucose concentrations were determined immediately before and 2 hours after each meal. Steroid-induced diabetes mellitus was diagnosed if the patient had either a fasting glucose concentration of 126 mg/dl or greater, or a random glucose concentration of 200 mg/dl or greater. The patients were divided into two groups on the basis of whether SDM had developed (13 patients) or not (12 patients). Ages, body mass indexes, cumulative total doses and daily doses of prednisolone, duration of therapy, and serum cholesterol and triglyceride concentrations were compared between the groups. Thirteen of the 25 patients were identified with SDM, and all of them had plasma glucose concentrations of 200 mg/dl or greater 2 hours after lunch. Mean age (59.1 +/- 10.2 yrs) and cholesterol concentration after prednisolone treatment (226.8 +/- 36.4 mg/dl) in the SDM group were significantly higher than those values in the non-SDM group (41.3 +/- 18.0 yrs and 188.1 +/- 27.2 mg/dl, respectively, p<0.01). CONCLUSIONS: A close relationship among postprandial hyperglycemia, advanced age, and hypercholesterolemia is a characteristic of SDM in patients with neurologic diseases. Therefore, monitoring the plasma glucose concentration 2 hours after lunch may be useful to detect SDM in these patients.     

不同剂量甲泼尼龙静脉治疗风湿性疾病对血糖影响的前瞻性对照研究

目的 分析静脉应用不同剂量甲泼尼龙对患者治疗最初3 d空腹、早餐后、午餐后及晚餐后血糖的影响.方法 选择2008年5月至2010年9月80例因风湿性疾病需要应用甲泼尼龙静脉点滴治疗的住院患者.所有患者既往均无糖尿病或糖耐量异常史,无口服或静脉应用糖皮质激素病史.甲泼尼龙用量≤80 mg为常规剂量组,共40例;用量≥200 mg为冲击剂量组,共40例.分别检测每例患者入院时空腹、应用甲泼尼龙第1、2、3天的快速血糖值(包括空腹、早餐后、午餐后、晚餐后),以及应用激素1个月后的空腹血糖值.结果 2组同一时间点的血糖值比较差异无统计学意义(P＞0.05).80例患者不同时间血糖值的比较结果显示,第1、2、3天的早餐后血糖[分别为(7.99±2.61)、(8.15±3.14)、(7.53±2.59)mmol/L]与这3天的中餐后血糖[分别为(11.80±3.43)、(11.73±3.52)、(10.88±3.63)mmol/L]及晚餐后糖[分别为(10.84±3.59)、(10.86±3.47)、(10.16±3.60)mmol/L]比较,差异均有统计学意义(P＜0.05);中餐后和晚餐后血糖比较,差异无统计学意义(P＞0.05).应用甲泼尼龙前和应用1月时的空腹血糖值比较,差异无统计学意义(P＞0.05).结论 静脉输注甲泼尼龙主要影响中餐及晚餐后血糖.血糖变化未显示出与甲泼尼龙剂量正相关,血糖增高呈一过性.

Abstract：

Objective To investigate the effects of Plasma glucose of different dose methylprednisolone therapies in the treatment of Rheumatoid diseases, including fasting plasma glucose examined and the levels of 2h postprandial glucose. Methods Eighty cases of patients of Rheumatoid diseases who had no Diabetes mellitus and no history of prednisone taking were selected during year 2008 to 2010. All the patients were divided into two groups. The normal dose group were forty patients who received the methylprednisolone ( ≤ 80 mg/day) and the large dose group were also forty patients who received the methylprednisolone( ≥200 mg/day). Compared the levels of fasting plasma glucose and the 2 h postprandial glucose in the first three days and the fasting plasma glucose after 1 month. Results The levels of the plasma glucose were not significantly changed in the two groups at the same point. The levels of the plasma glucose after breakfast were significantly different with the levels after lunch and dinner. There was no difference of the plasma glucose between the time before using methylprednisolone and one month. Conclusions The methylprednisolone infusion was mainly effect the plasma glucose levels after lunch and dinner. There was no dose-dependent phenomenon when using the methylprednisolone.