Analysis of the effect of seasonal administration on the efficacy of sitagliptin: Subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study.

AIMS/INTRODUCTION: Hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus fluctuate throughout the year. However, there are few studies that have evaluated the therapeutic effect of hypoglycemic agents while considering such fluctuations. In a multicenter study (Januvia Multicenter Prospective Trial in Type 2 Diabetes Study), pretreatment patients with type 2 diabetes mellitus were divided into seven groups and given sitagliptin for 1 year. The aim of the present study was to evaluate the differences in the therapeutic effect, and the efficacy of sitagliptin in patients with type 2 diabetes mellitus based on the month the administration of the drug began as a subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus were divided into four groups according to the month of initiation of sitagliptin. Changes in HbA1c in each group were compared at 3 and 12 months after administration of sitagliptin. As a negative correlation has been reported between baseline HbA1c and the degree of change after administration of sitagliptin, an analysis using the residual error from the approximate line was carried out. RESULTS: In the analysis of the degree of change in HbA1c, patients in the group in which administration of sitagliptin was started between August and October had the lowest degree of improvement at 3 months after starting sitagliptin. However, there was no significant intergroup difference in improvement at 12 months after the start of sitagliptin. The same result was also obtained in residual analysis. CONCLUSIONS: The present study suggested that the season of administration of sitagliptin influenced the subsequent hypoglycemic effect even after analysis excluding the influence of HbA1c value at the start of treatment. This study provides possibility, showing that seasonal fluctuations have an effect on the efficacy of antidiabetic drugs.

Erratum to: Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus and comparison of hypoglycemic action of concomitant medications: a subanalysis of the JAMP study.

[This corrects the article DOI: 10.1007/s13340-017-0330-2.].

Renal Function During an Open-Label Prospective Observational Trial of Sitagliptin in Patients With Diabetes: A Sub-Analysis of the JAMP Study.

BACKGROUND: The aim of the study was to determine the effects of sitagliptin on renal function in a diabetic population including patients with normal renal function. METHODS: We analyzed the association between 12-month, 50 mg/day sitagliptin and renal function in outpatients with type 2 diabetes mellitus and poor blood glucose control in a subset of patients in the larger Januvia Multicenter Prospective Trial in Type 2 Diabetes observational study. Stratified analyses of changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were performed. Factors associated with changes in eGFR at 3 months were examined by multivariate regression analysis. RESULTS: Of the 779 patients enrolled, 585 were followed up for 12 months. eGFR decreased significantly from baseline at 3 and 12 months in patients with a baseline eGFR of ≥ 90 mL/min/1.73 m2 and in those with a baseline eGFR of ≥ 60 to < 90 mL/min/1.73 m2. Conversely, eGFR tended to increase at 3 and 12 months in patients with a baseline eGFR of ≥ 45 to < 60 mL/min/1.73 m2 and in those with a baseline eGFR of ≥ 30 to < 45 mL/min/1.73 m2. UACR decreased significantly (-21.6 (-46.8, 7.8)) at 3 months in patients with a baseline UACR of ≥ 30 mg/g Cre. Multivariate regression analysis of factors associated with changes in eGFR at 3 months revealed that higher baseline eGFR and greater decline in UACR were associated with more conspicuous decreases in eGFR. CONCLUSIONS: In this group of diabetic patients receiving sitagliptin, eGFR declined in patients with high baseline eGFR, but not in those with a low baseline eGFR.

Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus and comparison of hypoglycemic action of concomitant medications: a subanalysis of the JAMP study.

PURPOSE: To determine the efficacy and safety of sitagliptin when used with some therapeutic drugs to treat elderly patients. METHODS: Sitagliptin (50 mg/day) was added to the pre-existing therapy for type 2 diabetes. Changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline, and exploratory analysis was performed. These analyses were conducted as subanalyses of the JAMP study, which was an open-label observational study. RESULTS: For patients who were ≥65 years of age, the change in HbA1c level from baseline ranged from -0.50 to -0.87% at 3 months after starting treatment. There was no significant difference in the change in HbA1c level between the patients treated with different concomitant drugs. No significant difference in HbA1c variations at 3 and 12 months from baseline was noted among the three age groups (≥75, 65-74, and <65 years). Multiple regression analysis was performed, and it revealed that patients with higher HbA1c levels at baseline were likely to show decreased HbA1c levels, while those with higher triglyceride (TG) levels were unlikely to show decreased HbA1c levels. CONCLUSION: Sitagliptin has the potential to both improve glycemic control and prevent hypoglycemia, and can be considered a potent alternative drug.

Factors involved in decreasing the therapeutic effect of sitagliptin: a subanalysis of the JAMP study.

OBJECTIVE: As a subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes (JAMP study), we examined factors that decreased blood glucose control effect of sitagliptin after 3 months and patients requiring an addition or increase of diabetes treatment. METHODS: We selected patients in whom glycated hemoglobin (HbA1c) levels decreased by month 3 after initiation of sitagliptin treatment and conducted two analyses: (1) in patients who did not change drugs until month 12, we compared changes in HbA1c levels between concomitant drugs and examined factors that decreased blood glucose control effect of sitagliptin; (2) compared changes in HbA1c levels and backgrounds between patients who did and did not require an addition to or increased dose of the antidiabetic agent. RESULTS: Four hundred and ninety-eight patients were chosen. In 369 patients without drug change until month 12, changes in HbA1c levels during months 3-12 were not significantly different among concomitant drugs; factors causing rebound HbA1c were smoking and weight gain. Patient characteristics were compared between those who did and did not require an additional drug or a dose increase (n = 114) (n = 384). Drug changes were associated with longer disease duration, younger age, higher rate of smoking, and higher degree of insulin resistance but not with concomitantly administered drugs. CONCLUSION: Smoking and weight gain were factors that decreased the effect of sitagliptin on reducing blood glucose levels. Differences in concomitant drugs did not affect sitagliptin's effects on glycemic control. A dose increase or the addition of the antidiabetic drug was not associated with concomitant drugs.

Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study.

BACKGROUND: To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs. METHODS: Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis. RESULTS: HbA1c levels were significantly decreased after 1 month of treatment compared to baseline, with a mean change in HbA1c level from baseline of -0.73% (range, -0.80 to -0.67) in the entire study population at 3 months. Patients who received a medium dose of glimepiride showed the least improvement in HbA1c levels. The percentage of patients who achieved an HbA1c level of <7.0% significantly increased after 1 month of treatment, reaching 53.1% at 3 months. The percentage of patients who achieved a fasting blood glucose level of <130 mg/dL significantly increased after 1 month of treatment, reaching 50.9% at 3 months. CONCLUSIONS: Sitagliptin improved the HbA1c level and rate of achieving the target control levels in patients with type 2 diabetes mellitus who were previously untreated with, or poorly responsive to, existing antidiabetic drugs. Thus, sitagliptin is expected to be useful in this patient group. However, the additional administration of sitagliptin in patients treated with medium-dose glimepiride only slightly improved blood glucose control when corrected for baseline HbA1c level.