Effects of miglitol, vildagliptin, or their combination on serum insulin and peptide YY levels and plasma glucose, cholecystokinin, ghrelin, and obestatin levels.

We previously reported that combination therapy with an α-glucosidase inhibitor (αGI) and a dipeptidyl peptidase-4 (DPP-4) inhibitor increased active glucagon-like peptide-1 (GLP-1) levels and decreased total glucose-dependent insulinotropic polypeptide (GIP) levels, compared with monotherapy, in non-diabetic men. However, the peptide YY (PYY), cholecystokinin (CCK), ghrelin, and obestatin levels in patients receiving a combination of αGIs and DPP-4 inhibitors have not been previously reported. We evaluated the effect of miglitol, vildagliptin, or their combination on these parameters. Miglitol and/or vildagliptin were administered according to four different intake schedules in eleven non-diabetic men (C: no drug, M: miglitol; V: vildagliptin, M+V: miglitol+vildagliptin). Blood samples were collected at 0, 30, 60, and 120 min after the start of breakfast. The plasma glucose, serum insulin, serum total PYY (PYY1-36 and PYY3-36), plasma CCK, plasma active ghrelin, and plasma obestatin levels were measured. The area under the curve (AUC) of the serum total PYY level in the M group was significantly greater than that in the C group, and the AUC of the serum total PYY level in the M+V group was significantly lower than that in the M group. The combination therapy did not change the AUC of the plasma CCK, plasma active ghrelin, plasma obestatin, and ghrelin/obestatin levels, compared with the control. The results of our study suggested that combination therapy with miglitol and vildagliptin had no effect on appetite regulation hormones, such as total PYY, CCK, active ghrelin, and obestatin, compared with the levels in the control group.

Second-line treatments for dyslipidemia in patients at risk of cardiovascular disease.

Previous studies have shown that approximately 50% patients at risk of cardiovascular disease do not achieve lipid management goals. Thus, improvements dyslipidemia management are needed. We investigated the clinical choice and efficacy of second-line treatments for dyslipidemia in the Japanese clinical setting. Using a retrospective cohort design, we collected lipid profile data from patients who had been treated with hypolipidemic agents at a stable dosage for at least 12 weeks. These patients had then been administered a second-line treatment for dyslipidemia because they had not achieved the low-density lipoprotein cholesterol (LDL-C) management goals. We included data from 641 patients in our analysis. The top three choices for second-line treatment were adding ezetimibe, switching to strong statins (statin switching), and doubling the original statin dosage (statin doubling). Adding ezetimibe, statin switching, and statin doubling decreased LDL-C levels by 28.2 ± 14.5%, 23.2 ± 24.4%, and 23.5 ± 17.2%, respectively. Among these three strategies, adding ezetimibe decreased LDL-C levels to the maximum extent. In patients with dysglycemia, baseline-adjusted change in hemoglobin A1c (HbA1c) levels decreased slightly in the adding-ezetimibe, statin-switching, and statin-doubling groups, but the differences were not statistically significant among the groups (-0.10 ± 0.62%, -0.22 ± 0.54%, and -0.12 ± 0.52%, p = 0.19). In conclusion, the most common second-line treatment options for dyslipidemia were adding ezetimibe, statin switching, or statin doubling. Adding ezetimibe resulted in the highest reduction in LDL-C levels. These strategies did not increase HbA1c levels when administered with conventional diabetes treatment.

A Randomized Controlled Trial of a Mini Low-Carbohydrate Diet and an Energy-Controlled Diet Among Japanese Patients With Type 2 Diabetes.

BACKGROUND: Low-carbohydrate diets have been shown to effectively improve the metabolic status of patients with type 2 diabetes mellitus. However, patients may find it challenging to maintain a strict low-carbohydrate diet. The objective of this study was to determine if a one-meal, low-carbohydrate diet is as effective in improving metabolic status as a conventional, energy-restricted diet among patients with type 2 diabetes mellitus. METHODS: In this 12-week randomized controlled study, the primary endpoint was differences in the changes of plasma glycosylated hemoglobin (HbA1c) levels between the two experimental groups. Since the two groups had differences in body weight, body mass index, and waist circumference, propensity score matching was used to assess HbA1c outcomes via cohort pairs according to age, sex, body weight, HbA1c level, and waist circumference. RESULTS: There were no differences in the changes in HbA1c between the two groups (P = 0.95). In addition, there were no differences in the changes in glycated albumin, 1,5-anhydroglucitol, lipid profile, body weight, waist circumference, and fat mass between the two groups. The mini low-carbohydrate diet group had an increased protein intake (P = 0.0085), as compared with the control group. However, neither group showed changes in their Diabetes Treatment Satisfaction Questionnaire score. CONCLUSION: Either diet would be effective for improving the metabolic status of this study population.

Correction to: A Randomized Controlled Trial of a Mini Low-Carbohydrate Diet and an Energy-Controlled Diet Among Japanese Patients With Type 2 Diabetes.

[This corrects the article DOI: 10.14740/jocmr3281w.].

Effect of Switching From an Anti-Diabetic Loose Dose Combination to a Fixed Dose Combination Regimen at Equivalent Dosage for 6 Months on Glycemic Control in Japanese Patients With Type 2 Diabetes: A Pilot Study.

BACKGROUND: Patients with type 2 diabetes mellitus often take multiple anti-diabetic drugs for a long period. Fixed dose combination (FDC) therapy is expected to improve drug adherence for patients with diabetes. The effect of switching from a loose dose combination (LDC) regimen to an FDC regimen at equivalent dosage on glycemic control has not been evaluated fully. Therefore, we investigated the effect of switching from LDC to FDC at equivalent dosage for 6 months on glycemic control in Japanese patients with type 2 diabetes. METHODS: Thirty-eight Japanese patients with type 2 diabetes who were taking anti-diabetic drugs including pioglitazone + metformin, pioglitazone + alogliptin, or pioglitazone + glimepiride were enrolled. These drugs were switched to an FDC of Metact®, Liobel® or Sonias®, respectively, at equivalent dosage. Other anti-diabetic drugs and units of insulin were not changed during the study if possible. HbA1c and body weight were measured 0, 2, 4 and 6 months after switching from an LDC to FDC. We also conducted a questionnaire survey 2 months after the start of the FDC regimen. RESULTS: HbA1c levels at 2, 4, and 6 months were not significantly changed compared with prior to switching from an LDC to FDC regimen. Moreover, 74.2% of patients considered decreasing the number of drugs to be "very good" or "good". CONCLUSION: HbA1c levels did not differ between patients receiving LDC and FDC therapy at equivalent dosage in this study.

Comparison of Plasma Glucose and Gut Hormone Levels Between Drinking Enteral Formula Over a Period of 5 and 20 Minutes in Japanese Patients With Type 2 Diabetes: A Pilot Study.

BACKGROUND: A fast eating speed is reportedly associated with obesity, fatty liver, and metabolic syndrome. As a comparison of postprandial glucose levels after eating quickly or slowly has not been previously reported for Japanese patients with type 2 diabetes, we evaluated the impact of the fast or slow ingestion of an enteral formula (liquid meal) on glucose metabolism. METHODS: Ten Japanese patients with type 2 diabetes who had been hospitalized at our hospital were enrolled. All the subjects received an enteral formula for breakfast. The study was performed over a 2-day period in each subject (day 1: enteral formula was consumed over a 5-minute period; day 2: enteral formula was consumed over a 20-minute period). The subjects were requested to fast for at least 12 hours before eating breakfast, and blood samples were collected at 0, 30, 60, and 120 min after the start of breakfast. RESULTS: The areas under the curve (AUCs) of the plasma glucose, serum insulin, plasma active ghrelin, glucagon-like peptide-1 (GLP-1), plasma total glucose-dependent insulinotropic polypeptide (GIP), and serum total peptide YY (PYY) levels were not significantly changed by intake over a 5-minute or 20-minute period. CONCLUSIONS: Eating quickly per se probably does not affect postprandial glucose excursions, but the increased energy intake resulting from eating quickly may increase the body weight and increase insulin resistance. Eating quickly may increase energy intake and worsen long-term metabolic parameters.

Effect of Switching from Sulphonylurea to Repaglinide Twice or Three Times Daily for 4 Months on Glycemic Control in Japanese Patients with Type 2 Diabetes.

Objective Switching from sulfonylureas to repaglinide in patients with type 2 diabetes improves glycemic control; however, the optimal dosage has not been fully evaluated. We designed to show that repaglinide was equivalent to sulfonylurea in Japanese patients with type 2 diabetes. We herein evaluated whether we could switch from sulfonylureas to repaglinide twice or thrice daily in Japanese adult patients who had been treated with anti-diabetic drugs, including sulfonylureas, and whose conditions were moderately well-controlled. Methods A total of 78 patients taking less than half the Japanese maximum dose of sulfonylurea were randomized into three groups: 26 in group A (switching from sulfonylureas to taking 0.25 or 0.5 mg of repaglinide just before breakfast and dinner twice daily), 27 in group B (switching from sulfonylureas to taking 0.25 or 0.5 mg of repaglinide just before meals thrice daily), and 25 in group C (continuing to take sulfonylurea). Blood samples were collected at 0, 1, 2, 3, and 4 months following the initiation of the maintenance period. Results The HbA1c and glycoalbumin levels did not significantly differ among the three groups after 4 months of treatment. Conclusion With the assumption that 1 mg of glimepiride is equivalent to 1.25 mg of glibenclamide or 40 mg of gliclazide, the administration of repaglinide (0.44 mg/meal) twice and thrice daily is similar to the efficacy of sulfonylurea (glimepiride 1.63-1.98 mg/day) after four months of treatment in Japanese patients with moderately well-controlled type 2 diabetes (HbA1c, 7-7.5%).

Anagliptin decreases serum lathosterol level in patients with type 2 diabetes: a pilot study.

OBJECTIVE: The mechanism responsible for the lipid-lowering effect of dipeptidyl peptidase-4 (DPP-4) inhibitors remains unknown in humans. We evaluated the effect of anagliptin on serum lipid profiles, including cholesterol synthesis and absorption markers, in Japanese patients with type 2 diabetes. METHODS: Thirty patients with type 2 diabetes (20 - 70 years old, low-density lipoprotein cholesterol (LDL-C) level over 120 mg/dl, and no history of treatment with antidiabetic or antihyperlipidemic drugs) were enrolled. One hundred milligrams of anagliptin were administered twice a day for a month. RESULTS: After treatment of anagliptin, the LDL-C and total cholesterol (TC) levels did not decrease overall, but the TC level decreased significantly in 28 patients whose HbA1c levels decreased. Lathosterol decreased significantly, whereas no changes in campesterol, sitosterol or cholestanol were observed. CONCLUSION: These results of our study show no significant change in LDL-C, a tendency of decrease in TC and non-high-density lipoprotein cholesterol (non-HDL-C) after treatment of anagliptin for 1 month. Anagliptin therapy decreased the cholesterol synthesis marker lathosterol without changing cholesterol absorption markers.

Comparison of the administration of teneligliptin every day versus every other day in Japanese patients with type 2 diabetes: a randomized non-inferior test.

The half life (t1/2 ) of teneligliptin is 24.2 hours. Accordingly, we hypothesized that the administration of teneligliptin every other day might improve glycemic control. In this study, we evaluated the effectiveness of the administration of teneligliptin every other day in Japanese patients with type 2 diabetes. Fifty-one patients were randomly assigned to receive treatment with 20 mg of teneligliptin every day (Group A) or 20 mg of teneligliptin every other day (Group B) for 12 weeks. HbA1c, glycoalbumin (GA), 1,5-anhydroglucitol (1,5-AG), lipid, blood pressure, body weight, urine albumin-to-creatinine ratio, overall treatment satisfaction level, adverse events and drug adherence were all measured. Forty-seven patients completed this study, and the HbA1c, GA, and 1,5-AG levels in group B were found to be decreased to the same extent as those in group A. No distinct differences in the overall treatment satisfaction level, adverse events, or drug adherence were seen between the two groups at 12 weeks. The administration of teneligliptin every other day had a similar efficacy, patient satisfaction level, and safety compared with its administration every day. This information will be useful for reducing the economic load without changing the patients' satisfaction and glycemic control.

Effect of repaglinide, administered two or three times daily for 3 months, on glycaemic control in Japanese patients with type 2 diabetes mellitus.

OBJECTIVES: To compare the efficacy, safety and compliance of repaglinide, administered either two or three times daily, regarding glycaemic control in patients with type 2 diabetes mellitus. METHODS: Japanese adults with type 2 diabetes mellitus, who had been treated without sulphonylureas or glinides for >3 months, were randomly assigned to two groups to receive either 0.25 mg repaglinide, oral, twice daily (group A) or 0.25 mg repaglinide, oral, three times daily (group B). Glycosylated haemoglobin (HbA1c), glycoalbumin (GA) and 1,5-anhydroglucitol (1,5-AG) levels were measured at 0, 1, 2 and 3 months after treatment commenced. RESULTS: Out of 43 patients who enrolled (group A, n = 22; group B, n = 21), 33 patients completed the trial (group A, n = 16; group B, n = 17). No significant between-group differences in HbA1c, GA, or 1,5-AG levels were seen at 1-3 months. No severe hypoglycaemic episodes or other adverse events were observed. CONCLUSIONS: Minimal-dose repaglinide administered twice daily was similar in efficacy and safety to three-times-daily administration, in Japanese patients with type 2 diabetes mellitus. Administration of repaglinide twice daily could be an alternative regimen for patients who cannot take repaglinide three times daily.

Glycemic control after addition of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes showing inadequate response to thrice-a-day treatment with α-glucosidase inhibitors.

OBJECTIVE: We investigated the effect of addition of alogliptin, while continuing the α-glucosidase inhibitor (αGI) administration at the same or reduced dose, or discontinuing the drug, on the glycemic control in type 2 diabetic patients showing inadequate response to αGI treatment. RESEARCH DESIGN AND METHODS: A prospective, randomized, controlled, multicenter interventional study trial. Subjects were randomly assigned to treatment with alogliptin alone (Intake 0 group), or alogliptin in addition to an αGI administered once-/twice-/thrice-daily (Intake 1, 2 and 3 groups). MAIN OUTCOME MEASURES: Changes in glycemic control were measured. RESULTS: The HbA1c and glycoalbumin levels at 1 and 3 months were significantly lower than the values at the baseline in the Intake 1, 2 and 3 groups, but not the Intake 0 group. The body weight at 3 months was significantly lower than that at the baseline in the Intake 3 group. There were no significant differences in the degree of satisfaction or participating volition recorded, before and after the start of the study treatments. CONCLUSIONS: Addition of alogliptin to once-/twice-daily administration of an αGI may be effective for obtaining improved glycemic control, without lowering the treatment satisfaction level, in type 2 diabetic patients.